c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor
Open accessAbstract
The ETS domain transcription factor PU.1 is necessary for the development of monocytes and regulates, in particular, the expression of the monocyte-specific macrophage colony-stimulating factor (M-CSF) receptor, which is critical for monocytic cell survival, proliferation, and differentiation. The bZIP transcription factor c-Jun, which is part of the AP-1 transcription factor complex, is also important for monocytic differentiation, but the monocyte-specific M-CSF receptor promoter has no AP-1 consensus binding sites. We asked the question of whether c-Jun could promote the induction of the M-CSF receptor by collaborating with PU.1. We demonstrate that c-Jun enhances the ability of PU.1 to transactivate the M-CSF receptor promoter as well as a minimal thymidine kinase promoter containing only PU.1 DNA binding sites. c-Jun does not directly bind to the M-CSF receptor promoter but associates via its basic domain with the ETS domain of PU.1. Consistent with our observation that AP-1 binding does not contribute to c-Jun coactivation is the observation that the activation of PU.1 by c-Jun is blocked by overexpression of c-Fos. Phosphorylation of c-Jun by c-Jun NH2-terminal kinase on Ser-63 and -73 does not alter the ability of c-Jun to enhance PU.1 transactivation. Activated Ras enhances the transcriptional activity of PU.1 by up-regulating c-Jun expression without changing the phosphorylation pattern of PU.1. The activation of PU.1 by Ras is blocked by a mutant c-Jun protein lacking the basic domain. The expression of this mutant form of c-Jun also completely blocks 12-O-tetradecanoylphorbol-13-acetate-induced M-CSF receptor promoter activity during monocytic differentiation. We propose therefore that c-Jun acts as a c-Jun NH2-terminal kinase-independent coactivator of PU.1, resulting in M-CSF receptor expression and development of the monocytic lineage.
AI snapshot
Written from the paper’s full text.
TL;DR
c-Jun acts as a JNK-independent coactivator of PU.1, enhancing PU.1-driven transactivation of the monocyte-specific M-CSF receptor promoter without binding DNA itself. Activated Ras increases c-Jun expression, and c-Jun function is required for TPA-induced M-CSF receptor promoter activity during monocytic differentiation.
Key findings
- c-Jun enhanced PU.1 transactivation of the M-CSF receptor promoter; in c-Jun-deficient F9 cells, PU.1 alone gave 2-fold activation, while PU.1 plus c-Jun gave 33-fold activation.
- c-Jun did not bind the M-CSF receptor promoter but physically associated with PU.1; c-Fos did not bind PU.1 and completely blocked c-Jun coactivation of PU.1.
- JNK phosphorylation of c-Jun at Ser-63 and Ser-73 was not required for coactivation: wild-type and S63A/S73A c-Jun enhanced PU.1 similarly, and activated Ras did not further enhance coactivator function.
- Activated Ras enhanced PU.1 transactivation by up-regulating c-Jun expression: Ras increased endogenous c-Jun protein 4-fold, estimated as 10-fold in transfected cells given 40% transfection efficiency; a c-Jun mutant lacking the basic domain blocked Ras- and TPA-induced M-CSF receptor promoter activity.
Methods
- Transient transfection reporter assays in CV-1, F9, 293T, and U937 cells using the human monocyte-specific M-CSF receptor promoter (bp −88 to +71), a minimal TK promoter with PU.1 sites or mutated PU.1 sites, and Renilla luciferase internal control; results are means ± S.E. of at least six independent experiments.
- Electrophoretic mobility shift assays with AP-1 and M-CSF receptor promoter probes, GST-PU.1 protein interaction assays with in vitro translated c-Jun or c-Fos, in vivo 32P labeling with phosphoamino acid analysis and phosphopeptide mapping, and Western blotting.
- U937 cells were differentiated with 2 × 10−7 M TPA or vehicle only.
Limitations
- The paper does not state explicit limitations.
- Evident from the text: the mechanistic conclusions rely heavily on transient overexpression in cell lines, including non-myeloid CV-1, F9, and 293T cells, rather than endogenous PU.1/c-Jun in primary monocytic cells.
- Evident from the text: the in vivo differentiation link is based on U937 reporter assays and TPA treatment, with no animal model or PU.1/c-Jun loss-of-function in primary hematopoietic development.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
Statistics
Claims the paper makes
19 of 94 cited sources checked · 11 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Mutants of PU.1 that lack the transcriptional activation domain are as efficient at stimulating enhancer activity as the wild-type PU.1 protein.
“In this context, mutants of PU.1 that lack the transcriptional activation domain are as efficient at stimulating enhancer activity as the wild-type PU.1 protein (60).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [60] Pongubala, 1997, Proc. Natl. Acad. Sci. U. S. A. source
The Results (Fig. 3E) report that PU.1 mutants lacking the transcriptional activation domain stimulated enhancer activity, but describe them as “nearly as efficient” as wild-type PU.1. The claim omits that qualification and states equal efficiency. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Premisecitation
c-Jun and PU.1 cooperate in the induction of other monocytic genes containing PU.1 and AP-1 DNA binding sites, such as the macrosialin gene and macrophage scavenger receptor gene.
“Moreover, c-Jun and PU.1 are already known to cooperate in the induction of other monocytic genes containing PU.1 and AP-1 DNA binding sites, such as the macrosialin gene (56) and macrophage scavenger receptor gene (57).”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [56] Li, 1998, J. Biol. Chem. source
- cites [57] Moulton, 1994, Mol. Cell. Biol. source
The Abstract (p. 4408) identifies PU.1-dependent and AP-1/ets regulatory elements that jointly contribute to macrophage scavenger receptor gene expression. It does not identify c-Jun as the AP-1 partner or show that c-Jun and PU.1 themselves cooperate; it describes the AP-1 complex as involving a distinct set of ets proteins. Citation 57 is attached to the scavenger receptor example, not the macrosialin example. (LLM, conf=0.85)
Experimental — accuracy not yet measured
- Premisecitation
The Ras signal transduction pathway induces the expression of c-Jun.
“The Ras signal transduction pathway, for example, induces the expression of c-Jun (51).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [51] Sistonen, 1989, EMBO J. source
- Premisecitation
The ability of PU.1 to rescue macrophage development in PU.1-/- ES cells is not impaired by these same phosphorylation mutants.
“Our data are in accordance with a report that the ability of PU.1 to rescue macrophage development in PU.1Ϫ/Ϫ ES cells is not impaired by these same phosphorylation mutants (67).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [67] Fisher, 1998, Mol. Cell. Biol. source
- Premisecitation
A PU.1 mutant at Ser-41 and -45 decreases the M-CSF- or granulocyte-macrophage colony-stimulating factor-dependent proliferation of bone marrow macrophages.
“and a PU.1 mutant at Ser-41 and -45 decreases the M-CSF-or granulocyte-macrophage colony-stimulating factor-dependent proliferation of bone marrow macrophages (54).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [54] Celada, 1996, J. Exp. Med. source
Figure 7B (p. 66) and the Discussion report that PU.1 mutations at Ser-41 and Ser-45 lowered proliferation of bone marrow-derived macrophages in the presence of M-CSF. The paper also reports GM-CSF-dependent proliferation, but those experiments tested PU.1 rather than the Ser-41/45 mutant; the mutant’s effect under GM-CSF is not established. (LLM, conf=0.87)
Experimental — accuracy not yet measured
- Findingown data
Co-transfection with an activated allele of Ras did not enhance the coactivator function of wild type or S63A/S73A c-Jun.
“co-transfection with an activated allele of Ras, which has been demonstrated to enhance the transcriptional activity of c-Jun via phosphorylation by JNK (34,46), did not enhance the coactivator function of wild type or S63A/S73A c-Jun (Fig. 3C).”
- Also stated in: § DISCUSSION · plain
“Furthermore, co-transfection with an activated allele of Ras, which has been demonstrated to enhance the transcriptional activity of c-Jun via phosphorylation by JNK (34,46), did not enhance the coactivator function of wild type or S63A/S73A c-Jun (Fig. 3C).”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · plain
- Findingown data
There is no difference in the ability of wild type c-Jun and S63A/S73A c-Jun to enhance PU.1 transactivation of the M-CSF receptor promoter in F9 cells.
“we found no difference in the ability of wild type c-Jun and S63A/S73A c-Jun to enhance PU.1 transactivation of the M-CSF receptor promoter in F9 cells (Fig. 3B).”
Quote in the paperSubstantial claim - Findingown data
Ras enhanced the transcriptional activity of known phosphorylation site mutants of PU.1 (Ser-41, -45, and -148) similar to wild type PU.1.
“Ras enhanced the transcriptional activity of known phosphorylation site mutants of PU.1 (Ser-41, -45, and -148) (53, 54) similar to wild type PU.1 (data not shown).”
Quote in the paperSubstantial claim - Findingown data
The transactivation domain of PU.1 (amino acids 1-118) is necessary for activation by c-Jun.
“The transactivation domain of PU.1 (amino acids 1-118) was necessary for the activation by c-Jun (Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
c-Jun enhances the ability of PU.1 to transactivate the human monocyte-specific M-CSF receptor promoter.
“Transfection of a c-Jun expression construct significantly enhanced the ability of PU.1 to transactivate the M-CSF receptor promoter (Fig. 1A).”
- Also stated in: § DISCUSSION · boosted
“Here we demonstrate that c-Jun enhances the ability of PU.1 to transactivate the human monocyte-specific M-CSF receptor promoter (Fig. 1, A and B).”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · boosted
- Findingown data
c-Jun specifically interacts with PU.1 in vitro.
“We were able to confirm that c-Jun did indeed specifically interact with PU.1 in vitro (Fig. 2B).”
Quote in the paperSubstantial claim - Findingown data
c-Fos did not bind to PU.1.
“c-Fos did not bind to PU.1 (Fig. 2B)”
Quote in the paperSubstantial claim - Findingown data
Ras up-regulated endogenous c-Jun protein expression 4-fold.
“but up-regulated endogenous c-Jun protein expression 4-fold (Fig. 4B).”
Quote in the paperSubstantial claim - Findingown data
In c-Jun-deficient F9 cells, co-expression of c-Jun with PU.1 led to robust transactivation (33-fold) of the M-CSF receptor promoter.
“while co-expression of c-Jun with PU.1 led to robust transactivation (33-fold) (Fig. 1B).”
Quote in the paperSubstantial claim - Findingown data
Co-transfection of c-Fos completely blocked the synergy between c-Jun and PU.1 in F9 cells.
“Co-transfection of c-Fos did not enhance the synergy between c-Jun and PU.1 but instead completely blocked it (Fig. 2C).”
Quote in the paperSubstantial claim - Findingown data
Ras did not change the protein expression of transfected PU.1.
“Ras did not change the protein expression of transfected PU.1 (Fig. 4B)”
Quote in the paperSubstantial claim - Findingown data
In c-Jun-deficient F9 cells, PU.1 weakly transactivated the M-CSF receptor promoter (2-fold).
“in c-Jun-deficient F9 cells, PU.1 weakly transactivated the M-CSF receptor promoter (2 fold)”
Quote in the paperSubstantial claim - Findingown data
A dominant negative c-Jun mutant lacking the basic domain blocked the activation of PU.1 by Ras.
“a dominant negative c-Jun mutant lacking the basic domain, which is required for physical interaction with PU.1 in vitro (44), blocked the activation of PU.1 by Ras (Fig. 4A).”
Quote in the paperSubstantial claim - Findingown data
MEKK1 enhanced the PU.1 transactivation function to a similar level as Ras.
“MEKK1 enhanced the PU.1 transactivation function to a similar level as Ras (Fig. 4A).”
Quote in the paperSubstantial claim - Findingown data
No effect of c-Jun on PU.1 activity was observed when the PU.1 binding sites were mutated.
“In control experiments, no effect of c-Jun on PU.1 activity was observed when the PU.1 binding sites were mutated (Fig. 1C).”
Quote in the paperSubstantial claim - Findingown data
c-Jun enhances PU.1 transactivation using a reporter construct containing four PU.1 binding sites cloned upstream of a minimal TK promoter.
“We observed enhanced PU.1 transactivation mediated by c-Jun using a reporter construct containing four PU.1 binding sites cloned upstream of a minimal TK promoter (Fig. 1C).”
Quote in the paperSubstantial claim - Findingown data
Activated Ras(L61) enhanced the ability of PU.1 to transactivate the M-CSF receptor promoter in CV-1 cells to a similar degree as c-Jun.
“activated Ras(L61) enhanced the ability of PU.1 to transactivate the M-CSF receptor promoter in CV-1 cells to a similar degree as c-Jun (Fig. 4A).”
Quote in the paperSubstantial claim - Findingown data
Co-expression of Ras did not alter the phosphorylation pattern of PU.1 in vivo.
“co-expression of Ras did not alter the phosphorylation pattern of PU.1 in vivo (Fig. 4C)”
Quote in the paperSubstantial claim - Findingown data
In vitro translated PU.1 bound strongly and specifically to the same M-CSF receptor promoter fragments.
“in vitro translated PU.1 was shown to bind strongly and specifically to the same M-CSF receptor promoter fragments (Fig. 2A).”
Quote in the paperSubstantial claim - Findingown data
c-Fos completely blocks the coactivation of PU.1 by c-Jun.
“In contrast, c-Fos completely blocks the coactivation of PU.1 by c-Jun (Fig. 2C).”
Quote in the paperSubstantial claim - Findingown data
c-Fos does not cooperate with c-Jun in its coactivator function.
“However, c-Fos does not cooperate with c-Jun in its coactivator function.”
Quote in the paperSubstantial claim - Findingown data
Ras enhanced the ability of PU.1 to transactivate the M-CSF receptor promoter in myeloid U937 cells.
“We first showed that Ras enhanced the ability of PU.1 to transactivate the M-CSF receptor promoter in myeloid U937 cells (Fig. 5A).”
- Also stated in: § DISCUSSION · plain
“In fact, Ras enhanced the ability of PU.1 to transactivate the M-CSF receptor promoter in myeloid U937 cells (Fig. 5A).”
Quote in the paperNot a substantial claim - Also stated in: § DISCUSSION · plain
- Findingown data
c-Jun physically binds to PU.1.
“Furthermore, c-Jun physically binds to PU.1 (Fig. 2B).”
Quote in the paperSubstantial claim - Findingown data
c-Jun cannot exert its coactivator function on PU.1 mutants that lack the transactivation domain.
“and c-Jun cannot exert its coactivator function on PU.1 mutants that lack the transactivation domain (Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
The effect of TPA on the human monocytic M-CSF receptor promoter was blocked by co-expression with a dominant negative c-Jun mutant lacking the basic domain.
“This effect on the human monocytic M-CSF receptor promoter was blocked by co-expression with a dominant negative c-Jun mutant lacking the basic domain (Fig. 5A).”
Quote in the paperSubstantial claim - Findingown data
c-Jun enhances the ability of PU.1 to transactivate a minimal promoter driven by PU.1 sites alone.
“and, moreover, enhances the ability of PU.1 to transactivate a minimal promoter driven by PU.1 sites alone (Fig. 1C).”
Quote in the paperSubstantial claim - Findingown data
TPA increased the expression of endogenous M-CSF receptor.
“and also increased the expression of endogenous M-CSF receptor (Fig. 5B).”
Quote in the paperSubstantial claim - Findingown data
c-Fos does not physically bind to PU.1.
“Since c-Fos does not physically bind to PU.1 (Fig. 2B), it might compete with PU.1 for the binding partner c-Jun.”
Quote in the paperSubstantial claim - Findingown data
There is no difference in the ability of wild type c-Jun and the S63A/S73A c-Jun mutant to enhance PU.1 transactivation of the M-CSF receptor promoter.
“Surprisingly, we found no difference in the ability of wild type c-Jun and the S63A/S73A c-Jun mutant to enhance PU.1 transactivation of the M-CSF receptor promoter (Fig. 3B).”
Quote in the paperSubstantial claim - Findingown data
c-Jun does not bind to the M-CSF receptor promoter.
“c-Jun does not bind to the M-CSF receptor promoter (Fig. 2A)”
Quote in the paperSubstantial claim - Findingown data
The leucine zipper domain of c-Jun is required for activation of PU.1.
“Since c-Fos blocks coactivation of PU.1 by c-Jun, the requirement of the leucine zipper domain of c-Jun for the activation of PU.1 (Fig. 3B) suggests that a c-Jun homodimer or heterodimer with a non-c-Fos partner mediates activation of the M-CSF receptor promoter.”
Quote in the paperSubstantial claim - Findingown data
The transactivation domain of PU.1 (amino acids 1-118) is necessary for the basal transactivation of the M-CSF receptor promoter by PU.1.
“In contrast, the transactivation domain of PU.1 (amino acids 1-118) is necessary for the basal transactivation of the M-CSF receptor promoter by PU.1 (Fig. 3A)”
Quote in the paperSubstantial claim - Findingown data
TPA increased reporter gene expression from the M-CSF receptor promoter construct.
“TPA increased reporter gene expression from our M-CSF receptor promoter construct (Fig. 5A)”
Quote in the paperSubstantial claim - Findingown data
MEKK1 enhances the PU.1 transactivation function to a similar level as Ras or c-Jun.
“In accordance with this model, another inducer of c-Jun expression, MEKK1 (40), enhanced the PU.1 transactivation function to a similar level as Ras or c-Jun (Fig. 4A).”
Quote in the paperNot a substantial claim - Findingown data
Ras enhances the ability of PU.1 to transactivate the M-CSF receptor promoter in c-Jun-containing CV-1 cells.
“whereas Ras enhances the ability of PU.1 to transactivate the M-CSF receptor promoter in c-Jun-containing CV-1 cells (Fig. 4A).”
Quote in the paperSubstantial claim - Findingown data
Ras induces c-Jun expression in CV-1 cells during activation of PU.1.
“and here we demonstrate that Ras induces c-Jun expression in CV-1 cells during activation of PU.1 (Fig. 4B).”
Quote in the paperSubstantial claim - Findingown data
The effect of TPA on the M-CSF receptor promoter is blocked by co-expression with a dominant negative c-Jun mutant lacking the basic domain, which interacts with PU.1.
“This effect on the M-CSF receptor promoter is blocked by co-expression with a dominant negative c-Jun mutant lacking the basic domain, which interacts with PU.1 (Fig. 5A).”
Quote in the paperSubstantial claim - Findingown data
Phosphorylation of c-Jun by JNK on Ser-63 and -73 does not alter the ability of c-Jun to enhance PU.1 transactivation.
“Phosphorylation of c-Jun by c-Jun NH 2 -terminal kinase on Ser-63 and -73 does not alter the ability of c-Jun to enhance PU.1 transactivation.”
Quote in the paperSubstantial claim - Findingown data
Co-expression of activated Ras does not alter the phosphoamino acid or phosphopeptide pattern of PU.1 in vivo.
“However, co-expression of activated Ras does not alter the phosphoamino acid (data not shown) or phosphopeptide pattern (Fig. 4C) of PU.1 in vivo.”
Quote in the paperSubstantial claim - Findingown data
c-Jun enhances the ability of PU.1 to transactivate the M-CSF receptor promoter.
“We demonstrate that c-Jun enhances the ability of PU.1 to transactivate the M-CSF receptor promoter as well as a minimal thymidine kinase promoter containing only PU.1 DNA binding sites.”
Quote in the paperSubstantial claim - Findingown data
A c-Jun mutant lacking the basic domain blocks the Ras enhancement of PU.1 transactivation of the M-CSF receptor promoter.
“Moreover, a c-Jun mutant lacking the basic domain blocks the Ras enhancement of PU.1 transactivation of the M-CSF receptor promoter (Fig. 4A).”
Quote in the paperSubstantial claim - Findingown data
Ras enhances the transcriptional activity of known phosphorylation site mutants of PU.1 (Ser-41, -45, and -148) similar to wild type PU.1.
“Furthermore, Ras enhances the transcriptional activity of known phosphorylation site mutants of PU.1 (Ser-41, -45, and -148) (53, 54) similar to wild type PU.1 (data not shown).”
Quote in the paperSubstantial claim - Findingown data
In c-Jun-deficient F9 cells there is no effect of Ras on PU.1.
“because in c-Jun-deficient F9 cells there is no effect of Ras on PU.1 (Fig. 3C)”
Quote in the paperSubstantial claim - Interpretationown data
c-Jun augmentation of PU.1 transactivation is not mediated by DNA binding of c-Jun.
“our data suggested that c-Jun augmentation of PU.1 transactivation was not mediated by DNA binding of c-Jun.”
- Also stated in: § RESULTS · hedged
“These results indicate that binding of c-Jun to the M-CSF receptor promoter DNA is not required to mediate its activating effect on PU.1.”
Quote in the paperSubstantial claim - Also stated in: § RESULTS · hedged
- Interpretationown data
The coactivator function of c-Jun to enhance the transcriptional activity of PU.1 is independent of JNK phosphorylation.
“These data indicate that the coactivator function of c-Jun to enhance the transcriptional activity of PU.1 is independent of JNK phosphorylation.”
- Also stated in: § DISCUSSION · hedged
“Our data indicate that the coactivator function of c-Jun to enhance the transcriptional activity of PU.1 is independent of JNK phosphorylation.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · hedged
- Interpretationreasoning
c-Jun acts as a coactivator of PU.1.
“Because c-Jun can bind to PU.1 but does not bind to DNA itself (Fig. 2A), we therefore conclude that c-Jun acts as a coactivator (45) of PU.1.”
- Also stated in: § DISCUSSION · plain
“Since c-Jun binds to PU.1 and functionally activates PU.1 without binding to the M-CSF receptor promoter DNA, we conclude that c-Jun acts as a coactivator (45) of PU.1.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [45] Janknecht, 1996, Nature source
- Also stated in: § DISCUSSION · plain
- Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (
Stable transfection of c-Jun into myeloid cell lines results in partial differentiation.
“stable transfection of c-Jun into myeloid cell lines results in partial differentiation (23,24).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [23] Szabo, 1994, Cell Growth Differ.
- cites [24] Li, 1994, Cell Growth Differ.
- Interpretationown data
PU.1 binding to DNA is necessary for its activation by c-Jun.
“These data indicate that PU.1 binding to DNA is necessary for its activation by c-Jun”
Quote in the paperSubstantial claim - Interpretationreasoning
Ras up-regulated c-Jun expression 10-fold in transfected cells.
“Since the transfection efficiency in the CV-1 cells was 40% (Fig. 4B), we estimate that Ras up-regulated c-Jun expression 10-fold in transfected cells.”
Quote in the paperNot a substantial claim - Premisecitation
c-Jun and PU.1 can physically interact.
“In these same studies, it was reported that c-Jun and PU.1 could physically interact, although the functional consequences of this interaction were not examined.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [44] Bassuk, 1995, Immunity source
- Interpretationreasoning
c-Fos might compete with PU.1 for the binding partner c-Jun.
“and therefore might compete with PU.1 for the binding partner c-Jun.”
- Also stated in: § DISCUSSION · hedged
“Since c-Fos does not physically bind to PU.1 (Fig. 2B), it might compete with PU.1 for the binding partner c-Jun.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · hedged
- Interpretationown data
The cooperation of c-Jun with PU.1 is important for M-CSF receptor promoter activity.
“The cooperation of c-Jun with PU.1 is therefore important for M-CSF receptor promoter activity.”
Quote in the paperSubstantial claim - Interpretationown data
PU.1 binding sites are sufficient to mediate c-Jun-enhanced PU.1 activation.
“and that PU.1 binding sites are sufficient to mediate this effect.”
Quote in the paperSubstantial claim - Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (
The monocyte-specific M-CSF receptor promoter contains no AP-1 consensus binding sites.
“the monocyte-specific M-CSF receptor promoter (9,26,27) contains no AP-1 consensus binding sites.”
- Also stated in: § RESULTS · plain
“Since there are no AP-1 consensus sites in the human monocyte-specific M-CSF receptor promoter from bp Ϫ88 to ϩ71 with respect to the major monocytic transcription start site (9, 26)”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [9] Zhang, 1994, Mol. Cell. Biol.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [26] Zhang, 1994, Mol. Cell. Biol.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [27] Zhang, 1996, Mol. Cell. Biol. source
- Also stated in: § RESULTS · plain
- Interpretationown data
c-Jun function is required for the increase in M-CSF receptor promoter activity observed in myeloid cells differentiated toward the monocytic lineage with TPA.
“These results indicate that c-Jun function is required for the increase in M-CSF receptor promoter activity observed in myeloid cells differentiated toward the monocytic lineage with TPA.”
- Also stated in: § DISCUSSION · hedged
“These results indicate that c-Jun function is required for the increase in M-CSF receptor promoter activity observed in myeloid cells differentiated toward the monocytic lineage with TPA.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · hedged
- Premisecitation
U937 cells can be differentiated to monocytic cells upon treatment with TPA.
“U937 cells can be differentiated to monocytic cells upon treatment with TPA”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] Hass, 1997, Leuk. Res. source
- Interpretationown data
Ras enhances the transcriptional activity of PU.1 by increasing the expression of its coactivator c-Jun.
“In conclusion, these data suggest a model in which Ras enhances the transcriptional activity of PU.1 by increasing the expression of its coactivator c-Jun.”
Quote in the paperSubstantial claim - Interpretationreasoning
A c-Jun homodimer or heterodimer with a non-c-Fos partner mediates activation of the M-CSF receptor promoter.
“Since c-Fos blocks coactivation of PU.1 by c-Jun, the requirement of the leucine zipper domain of c-Jun for the activation of PU.1 (Fig. 3B) suggests that a c-Jun homodimer or heterodimer with a non-c-Fos partner mediates activation of the M-CSF receptor promoter.”
Quote in the paperSubstantial claim - Interpretationown data
This is the first report demonstrating a coactivator function for c-Jun.
“This is the first report demonstrating a coactivator function for c-Jun.”
Quote in the paperSubstantial claim- Rests on an assumption: The human monocyte-specific M-CSF receptor promoter contains no AP-1 consensus binding sites.
- Interpretationreasoning
The regulation of c-Jun expression might be crucial for the capacity of c-Jun to coactivate PU.1 and induce monocytic differentiation.
“Since the coactivator function of c-Jun cannot be regulated via phosphorylation by JNK, the regulation of c-Jun expression might be crucial for the capacity of c-Jun to coactivate PU.1 and induce monocytic differentiation.”
Quote in the paperSubstantial claim - Interpretationown data
Ras activates the M-CSF receptor promoter via c-Jun and PU.1.
“Our data suggest that Ras activates the M-CSF receptor promoter via c-Jun and PU.1, because in c-Jun-deficient F9 cells there is no effect of Ras on PU.1 (Fig. 3C), whereas Ras enhances the ability of PU.1 to transactivate the M-CSF receptor promoter in c-Jun-containing CV-1 cells (Fig. 4A).”
Quote in the paperSubstantial claim- Rests on an assumption: Ras has not previously been shown to increase activity of the monocyte-specific M-CSF receptor promoter.
- Interpretationown data
AP-1 binding does not contribute to c-Jun coactivation.
“Consistent with our observation that AP-1 binding does not contribute to c-Jun coactivation is the observation that the activation of PU.1 by c-Jun is blocked by overexpression of c-Fos.”
Quote in the paperSubstantial claim- Rests on an assumption: The human monocyte-specific M-CSF receptor promoter contains no AP-1 consensus binding sites.
- Interpretationown data
c-Jun is a JNK-independent coactivator of PU.1.
“In summary, our data indicate that c-Jun is a JNK-independent coactivator of PU.1 (Fig. 5C).”
Quote in the paperSubstantial claim - Interpretationown data
Ras enhances the transcriptional activity of PU.1 by up-regulating the expression of its coactivator c-Jun.
“Thus, these data suggest that Ras enhances the transcriptional activity of PU.1 by up-regulating the expression of its coactivator c-Jun.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 39
- May combine two claims. 28
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (PU.1 plays a pivotal role in the development of myeloid and B cells.
“and plays a pivotal role in their development (3,4).”
Quote in the paperNot a substantial claim1 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (PU.1-deficient hematopoietic cells display minimal expression of G-CSF and GM-CSF receptors and no detectable M-CSF receptors.
“PU.1-deficient hematopoietic cells display minimal expression of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor receptors and no detectable M-CSF receptors (11,12).”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [11] Anderson, 1998, Blood source
- cites [12] Iwama, 1998, Nucleic Acids Res. source
The ‘mRNA expression of myeloid CSF receptors in mutant mice’ section reports markedly decreased G-CSF receptor mRNA and GM-CSF receptor mRNA undetectable by northern blot in PU.1-deficient fetal liver, although GM-CSF receptor mRNA had been detected by RT-PCR. Contrary to the claim’s last part, it reports that M-CSF receptor mRNA was decreased but detectable. The Discussion likewise says M-CSF and G-CSF receptors remained expressed at low levels. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (There is evidence that c-Jun plays a role in monocytic differentiation.
“there is evidence that c-Jun plays a role in monocytic differentiation.”
Quote in the paperNot a substantial claim1 of 5 sources checked- cites [20] Lord, 1993, Mol. Cell. Biol. source
- cites [21] Mollinedo, 1993, Biochem. J. source
- cites [22] Gaynor, 1991, Blood source
- cites [23] Szabo, 1994, Cell Growth Differ.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [24] Li, 1994, Cell Growth Differ.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (c-Jun mRNA is up-regulated upon monocyte differentiation of bipotential myeloid cell lines.
“c-Jun mRNA is up-regulated upon monocyte differentiation of bipotential myeloid cell lines (20 -22)”
Quote in the paperNot a substantial claim1 of 3 sources checked- cites [20] Lord, 1993, Mol. Cell. Biol. source
The paper’s opening passage identifies c-jun as a myeloid-differentiation primary response gene expressed after induced terminal differentiation of M1 cells. It does not establish the more specific claim that c-Jun mRNA is up-regulated during monocyte differentiation of bipotential myeloid cell lines. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [21] Mollinedo, 1993, Biochem. J. source
- cites [22] Gaynor, 1991, Blood source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRas is known to modulate the activity of the ETS domain transcription factors ETS-1 and ETS-2 by phosphorylation.
“Ras is known to modulate the activity of the ETS domain transcription factors ETS-1 and ETS-2 by phosphorylation (52).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [52] Yang, 1996, Mol. Cell. Biol. source
Classified as probably not a substantial claim.
PremisecitationRas signal transduction plays an important role in myeloid differentiation.
“Ras signal transduction has been demonstrated to play an important role in myeloid differentiation (47)(48)(49)(50)”
Quote in the paperSubstantial claim1 of 4 sources checked- cites [47] Jin, 1995, Mol. Cell. Biol. source
- cites [48] Hibi, 1993, Blood source
- cites [49] Maher, 1996, Leukemia
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [50] Skorski, 1992, J. Exp. Med. source
The discussion (pp. 747–748) links N-ras to growth-factor-dependent signaling and reports that it is required for the growth of some myeloid progenitors. It describes a role in coordinating proliferation and differentiation as likely, but the reported experiments measure colony growth rather than directly demonstrating a role in myeloid differentiation. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim.
PremisecitationRas is known to induce the expression of c-Jun.
“Ras is known to induce the expression of c-Jun (51).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [51] Sistonen, 1989, EMBO J. source
May combine two claims.
PremisecitationThe macrosialin promoter and macrophage scavenger receptor promoter contain PU.1 and AP-1 binding sites that are critical for their monocyte-specific expression.
“In contrast, the macrosialin promoter and macrophage scavenger receptor promoter contain PU.1 and AP-1 binding sites, which are critical for their monocyte-specific expression (56,57).”
Quote in the paperNot a substantial claim1 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe immunoglobulin 3' enhancer is activated by PU.1, c-Jun, PIP, and c-Fos and contains respective DNA binding sites for these factors.
“The immunoglobulin 3Ј enhancer is activated by PU.1, c-Jun, PIP, and c-Fos and contains respective DNA binding sites for these factors (60).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [60] Pongubala, 1997, Proc. Natl. Acad. Sci. U. S. A. source
May combine two claims.
Premisecitationc-Jun and the regulation of the M-CSF receptor by PU.1 both play important roles in the development of the monocytic lineage.
“The transcription factor c-Jun (20 -24) and the regulation of the M-CSF receptor by the transcription factor PU.1 (11,12,55) both play important roles in the development of the monocytic lineage.”
Quote in the paperSubstantial claim2 of 8 sources checked- cites [20] Lord, 1993, Mol. Cell. Biol. source
The paper’s summary (page not provided) identifies c-jun as a myeloid differentiation response gene and says fos/jun factors promote myeloid differentiation. It does not establish a distinct role for c-Jun in development of the monocytic lineage specifically. The PU.1/M-CSF receptor clause has separate citations and is not attributed to this source. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [21] Mollinedo, 1993, Biochem. J. source
- cites [22] Gaynor, 1991, Blood source
- cites [23] Szabo, 1994, Cell Growth Differ.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [24] Li, 1994, Cell Growth Differ.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [11] Anderson, 1998, Blood source
- cites [12] Iwama, 1998, Nucleic Acids Res. source
The Introduction says PU.1 regulates the M-CSF receptor promoter, and the receptor-expression section reports markedly decreased M-CSF receptor mRNA in PU.1-deficient fetal liver. But the Discussion says the role of myeloid CSF receptors in the developmental defects remains to be defined, so this paper does not establish that PU.1’s regulation of the receptor plays an important role in monocytic development. The c-Jun clause has separate citations and is not assessed against this source. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [55] Henkel, 1996, Blood source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRas modulates the activity of ETS domain transcription factors such as ETS-1 or ETS-2 by phosphorylation.
“Ras modulates the activity of ETS domain transcription factors such as ETS-1 or ETS-2 by phosphorylation (52).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [52] Yang, 1996, Mol. Cell. Biol. source
Classified as probably not a substantial claim.
PremisecitationThe activity of PU.1 is known to be regulated by phosphorylation.
“and the activity of PU.1 is known to be regulated by phosphorylation (53,54,65).”
Quote in the paperSubstantial claim1 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationM-CSF, granulocyte-macrophage colony-stimulating factor, or interleukin-3-induced monocytopoiesis of CD34+ cells is inhibited by N-Ras antisense oligonucleotides.
“In addition, M-CSF, granulocyte-macrophage colony-stimulating factor, or interleukin-3-induced monocytopoiesis of CD34ϩ cells is inhibited by N-Ras antisense oligonucleotides (50).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [50] Skorski, 1992, J. Exp. Med. source
May combine two claims.
Findingown dataThe transactivation domain of c-Jun (amino acids 1-87), the basic domain, and the leucine zipper domain are all necessary for activation of PU.1 by c-Jun.
“The transactivation domain of c-Jun (amino acids 1-87); the basic domain of c-Jun, which can physically interact with PU.1 (44) and mediates DNA binding to AP-1 sites; and the leucine zipper domain, which is responsible for homodimerization and heterodimerization with c-Fos, were all necessary for the activation of PU.1 by c-Jun (Fig. 3B).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn vitro translated c-Jun or a mixture of c-Jun and c-Fos specifically bound to a double-stranded AP-1 oligonucleotide probe from the collagenase promoter.
“In vitro translated c-Jun or a mixture of c-Jun and c-Fos specifically bound to a doublestranded AP-1 oligonucleotide probe from the collagenase promoter (Fig. 2A)”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataNo specific binding of c-Jun or c-Jun/c-Fos was observed using the double-stranded bp -88 to +71 M-CSF receptor promoter or bp -62 to -29 oligonucleotide containing the PU.1 binding site.
“while no specific binding was observed using the double-stranded bp Ϫ88 to ϩ71 M-CSF receptor promoter (Fig. 2A) or bp Ϫ62 to Ϫ29 oligonucleotide containing the PU.1 binding site of the M-CSF receptor promoter (data not shown).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataTPA increased reporter gene expression from the M-CSF receptor promoter construct and also increased the expression of endogenous M-CSF receptor.
“TPA increased reporter gene expression from our M-CSF receptor promoter construct (Fig. 5A) and also increased the expression of endogenous M-CSF receptor (Fig. 5B).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown datac-Jun does not directly bind to the M-CSF receptor promoter but associates via its basic domain with the ETS domain of PU.1.
“c-Jun does not directly bind to the M-CSF receptor promoter but associates via its basic domain with the ETS domain of PU.1.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (The M-CSF receptor is critical for monocytic cell survival, proliferation, and differentiation.
“The M-CSF receptor is critical for monocytic cell survival, proliferation, and differentiation (3,13).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (PU.1 is preferentially expressed in myeloid and B cells.
“The ETS domain transcription factor PU.1 is preferentially expressed in myeloid and B cells (1,2)”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (Mice deficient in PU.1 display a complete block in development of monocytes, macrophages, and B cells.
“mice deficient in PU.1 display a complete block in development of monocytes, macrophages, and B cells (5,6).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe transcriptional activity of c-Jun is increased following phosphorylation on Ser-63 and -73 by JNK.
“The transcriptional activity of c-Jun is increased following phosphorylation on Ser-63 and -73 by JNK (34,46).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (During TPA-induced monocytic differentiation of U937 cells, c-Jun and M-CSF receptor mRNA expression increases.
“during 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced monocytic differentiation of U937 cells, c-Jun and M-CSF receptor mRNA expression increases (25).”
- Also stated in: § The Expression of the Mutant Form of c-Jun That Lacks the Basic Domain Completely Blocks TPA-induced M-CSF Receptor Promoter Activity during Monocytic Differentiation-We next asked the question of whether the coactivator function of c-Jun could play a biological role during monocytic differentiation in vivo. · plain
“during this process c-Jun and M-CSF receptor mRNA expression increases (25).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] Hass, 1997, Leuk. Res. source
- Also stated in: § The Expression of the Mutant Form of c-Jun That Lacks the Basic Domain Completely Blocks TPA-induced M-CSF Receptor Promoter Activity during Monocytic Differentiation-We next asked the question of whether the coactivator function of c-Jun could play a biological role during monocytic differentiation in vivo. · plain
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe c-Jun promoter contains important TPA response elements that preferentially bind heterodimers of c-Jun and ATF-2, both of which are activated upon phosphorylation by JNK.
“The c-Jun promoter contains important TPA response elements that preferentially bind heterodimers of c-Jun and ATF-2, both of which are activated upon phosphorylation by JNK (17)(18)(19).”
Quote in the paperNot a substantial claim0 of 3 sources checkedClassified as probably not a substantial claim.
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (Little is known about the signaling molecules or protein-protein interactions that modulate the effect of PU.1 to regulate the M-CSF receptor promoter activity.
“little is known about the signaling molecules or protein-protein interactions that modulate the effect of PU.1 to regulate the M-CSF receptor promoter activity (3,16).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (The responsiveness of hematopoietic progenitor cells to M-CSF is regulated at the level of M-CSF receptor expression.
“The responsiveness of hematopoietic progenitor cells to M-CSF is regulated at the level of M-CSF receptor expression (15).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] Olweus, 1996, Blood source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (c-Jun belongs to the bZIP group of DNA binding proteins and is a component of AP-1 transcription factor complexes.
“c-Jun belongs to the bZIP group of DNA binding proteins and is a component of AP-1 transcription factor complexes (17).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] Bohmann, 1987, Science source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitationc-Jun can physically and functionally interact with ETS-1.
“It has previously been reported that c-Jun can physically and functionally interact with ETS-1, which like PU.1 is an ETS family transcription factor (44).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44] Bassuk, 1995, Immunity source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor* (c-Jun forms homodimers or heterodimerizes with other Jun family members or with other bZIP proteins including Fos and ATF/CREB families.
“c-Jun forms homodimers or can heterodimerize with other Jun family members or with other bZIP proteins including members of the Fos and ATF/cAMP response element-binding protein (CREB) families (18,19).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Interpretationown datac-Jun mediates its effects through direct interactions with PU.1 and not by independent DNA binding to an AP-1 site.
“These results are consistent with a model in which c-Jun mediates its effects through direct interactions with PU.1 and not by independent DNA binding to an AP-1 site.”
- Also stated in: § DISCUSSION · hedged
“These results are consistent with a model in which c-Jun mediates its effects through direct interactions with PU.1 and not by independent DNA binding to an AP-1 site (Fig. 5C).”
Quote in the paperSubstantial claim- Also stated in: § DISCUSSION · hedged
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenPrior to autoradiography, the gel was stained with Coomassie Brilliant Blue to verify that the protein concentrations of GST-PU.1 and GST were the same in all lanes.
“Prior to autoradiography, the gel was stained with Coomassie Brilliant Blue (Bio-Rad) to verify that the protein concentrations of GST-PU.1 and GST were the same in all lanes.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitationc-Jun residues Ser-63 and -73 are required for CBP/p300 stimulation in vivo and CBP/p300 binding in vitro.
“Furthermore, the general coactivator CBP/p300 stimulates c-Jun-dependent transcription, and the c-Jun residues Ser-63 and -73 are required for CBP/p300 stimulation in vivo and CBP/p300 binding in vitro (58).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [58] Bannister, 1995, Oncogene
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRas plays an important role in myeloid differentiation.
“In particular, Ras has been demonstrated to play an important role in myeloid differentiation.”
Quote in the paperNot a substantial claim0 of 3 sources checkedClassified as probably not a substantial claim. May combine two claims.
Study design and conductcitationpRL-null was chosen as internal control plasmid because it was not transactivated by Ras or by PU.1, c-Jun, c-Fos, or MEKK1 in CV-1, F9, 293T, or U937 cells.
“pRL-null was chosen as internal control plasmid, because it was not transactivated by Ras (30) or by PU.1, c-Jun, c-Fos, or MEKK1 in CV-1, F9, 293T, or U937 cells (data not shown).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [30] Behre, 1999, Biotechniques source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRas exerts its effect on cell growth mainly via ETS and AP-1 transcription factors.
“Ras exerts its effect on cell growth mainly via ETS (63) and AP-1 (64) transcription factors.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [63] Wasylyk, 1994, Oncogene
- cites [64] Johnson, 1996, Mol. Cell. Biol. source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationDominant negative mutants of ETS-1, ETS-2, or PU.1 with just the DNA binding domain inhibit Ras activation of transcription and revert Ras-transformed cells.
“and dominant negative mutants of ETS-1, ETS-2, or PU.1 with just the DNA binding domain inhibit Ras activation of transcription and revert Ras-transformed cells (63).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [63] Wasylyk, 1994, Oncogene
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationUsually, c-Jun forms heterodimers with c-Fos in AP-1 transcription factor complexes.
“Usually, c-Jun forms heterodimers with c-Fos in AP-1 transcription factor complexes (17)(18)(19).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenResults are given as means ± S.E. of at least six independent experiments.
“Results are given as means Ϯ S.E. of at least six independent experiments.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMacrophage differentiation and M-CSF-dependent survival are altered in transgenic mice that express dominant suppressors of Ras signaling.
“Macrophage differentiation and M-CSF-dependent survival are altered in transgenic mice that express dominant suppressors of Ras signaling (47)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [47] Jin, 1995, Mol. Cell. Biol. source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationPU.1 binds to the B cell-specific immunoglobulin kappa (Ig) 3' enhancer and can control transcriptional activity.
“In accordance with its pivotal role in B cell development (5, 6), PU.1 binds to the B cell-specific immunoglobulin kappa (Ig) 3Ј enhancer and can control transcriptional activity (59).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [59] Pongubala, 1992, Mol. Cell. Biol. source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataIn parallel plates, luciferase activities were determined to ensure that Ras enhances the transactivation function of PU.1 in the particular experiment used in in vivo labeling and subsequent phosphoamino acid analysis and phosphopeptide mapping.
“In parallel plates, 0.3 g of the M-CSF receptor promoter was co-transfected in 293T cells, and luciferase activities were determined to ensure that Ras enhances the transactivation function of PU.1 in the particular experiment used in in vivo labeling and subsequent phosphoamino acid analysis and phosphopeptide mapping.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCells with a null mutation in the c-jun gene lack many characteristics of Ras transformation.
“For example, cells with a null mutation in the c-jun gene lack many characteristics of Ras transformation (64)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [64] Johnson, 1996, Mol. Cell. Biol. source
May combine two claims.
InterpretationreasoningThe function of different PU.1 domains might vary depending on the cell type (monocyte versus B cell) and on the cooperating proteins (c-Jun as part of the AP-1 transcription factor complex versus c-Jun as a JNK independent coactivator).
“These data suggest that the function of different PU.1 domains might vary depending on the cell type (monocyte versus B cell) and on the cooperating proteins (c-Jun as part of the AP-1 transcription factor complex versus c-Jun as a JNK independent coactivator).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe Ras family of proteins are GTP-dependent molecular switches that are essential for cell growth and differentiation.
“The Ras family of proteins are GTP-dependent molecular switches that are essential for cell growth and differentiation (61,62).”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
PremisecitationUsually, the transcriptional activity of c-Jun is increased following phosphorylation on Ser-63 and -73 by JNK.
“Usually, the transcriptional activity of c-Jun is increased following phosphorylation on Ser-63 and -73 by JNK (34,46).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCBP/p300 stimulates c-Jun-dependent transcription.
“Furthermore, the general coactivator CBP/p300 stimulates c-Jun-dependent transcription, and the c-Jun residues Ser-63 and -73 are required for CBP/p300 stimulation in vivo and CBP/p300 binding in vitro (58).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [58] Bannister, 1995, Oncogene
May combine two claims.
PremisecitationU937 cells can be differentiated with TPA to monocytic cells, and during this process c-Jun and M-CSF receptor mRNA expression increases.
“It has been shown that U937 cells can be differentiated with TPA to monocytic cells, and during this process c-Jun and M-CSF receptor mRNA expression increases (25).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] Hass, 1997, Leuk. Res. source
May combine two claims.
InterpretationreasoningIncreased c-Jun expression activates PU.1, resulting in increased M-CSF receptor up-regulation and survival, proliferation, and differentiation of the monocytic lineage.
“Increased c-Jun expression activates PU.1, resulting in increased M-CSF receptor up-regulation and survival, proliferation, and differentiation of the monocytic lineage.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataRas enhances the transcriptional activity of PU.1 by increasing the expression of its coactivator c-Jun without modifying the activity of PU.1 by phosphorylation.
“In conclusion, these results suggest a model in which Ras enhances the transcriptional activity of PU.1 by increasing the expression of its coactivator c-Jun without modifying the activity of PU.1 by phosphorylation.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationPU.1 can be phosphorylated by casein kinase or JNK in vitro.
“More-over, the ETS domain factor PU.1, in particular, can be phosphorylated by casein kinase (53,65) or JNK in vitro (66)”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationPhosphorylation of PU.1 at Ser-148 is necessary for interaction with NF-EM5 or stimulation by lipopolysaccharide.
“Phosphorylation of PU.1 at Ser-148 is necessary for interaction with NF-EM5 (53) or stimulation by lipopolysaccharide (65)”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
InterpretationreasoningGrowth factors or other signals activate the Ras pathway, which in turn increases c-Jun expression in monocytic progenitors.
“These results suggest a model in which growth factors or other signals (3,68) activate the Ras pathway, which in turn increases c-Jun expression in monocytic progenitors.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA number of hematopoietic cell lines undergo spontaneous monocytic differentiation in response to expression of activated Ras.
“while a number of hematopoietic cell lines undergo spontaneous monocytic differentiation in response to expression of activated Ras (48,49).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [48] Hibi, 1993, Blood source
- cites [49] Maher, 1996, Leukemia
The paper relies on this without support.
It has not been shown whether Ras increases the activity of the monocyte-specific M-CSF receptor promoter.
“it has not been shown whether Ras increases the activity of the monocyte-specific M-CSF receptor promoter.”
The paper relies on this without support.
The human monocyte-specific M-CSF receptor promoter contains no AP-1 consensus binding sites.
“The c-Jun enhancement of the ability of PU.1 to transactivate the M-CSF receptor promoter is novel, because the human monocyte-specific M-CSF receptor promoter contains no AP-1 consensus binding sites.”
The paper relies on this without support.
Ras has not previously been shown to increase activity of the monocyte-specific M-CSF receptor promoter.
“Although Ras signaling plays an important role in monocytic differentiation, Ras has not previously been shown to increase activity of the monocyte-specific M-CSF receptor promoter.”
The paper relies on this without support.
PU.1 is necessary for the development of monocytes and regulates the expression of the monocyte-specific M-CSF receptor, which is critical for monocytic cell survival, proliferation, and differentiation.
“The ETS domain transcription factor PU.1 is necessary for the development of monocytes and regulates, in particular, the expression of the monocyte-specific macrophage colony-stimulating factor (M-CSF) receptor, which is critical for monocytic cell survival, proliferation, and differentiation.”
The paper relies on this without support.
c-Jun is important for monocytic differentiation.
“The bZIP transcription factor c-Jun, which is part of the AP-1 transcription factor complex, is also important for monocytic differentiation, but the monocyte-specific M-CSF receptor promoter has no AP-1 consensus binding sites.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The evolutionarily conserved C-terminal ETS domain mediates PU.1 DNA binding and interaction with c-Jun, GATA-1, GATA-2, C/EBP-α and -β and AML-1.
“The evolutionarily conserved DNA binding domain (also known as ETS domain) is confined to the C-terminus of PU.1 and mediates its binding to DNA as well as interaction with a number of other proteins such as c-Jun, GATA-1, GATA-2, C/EBP-α and -β and AML-1[40–42].”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [40]
PU.1 mutants lacking the transactivation domain cannot interact with c-Jun.
“However, the mutants that lack the transactivation domain cannot interact with c-Jun [40].”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [40]
PU.1 cooperates with NF-IL6β (C/EBP-δ), c-Myb and C/EBP-α, and c-Jun and c-Fos.
“For example, PU.1 has been shown to cooperate with NF-IL6β (C/EBP-δ) [43], c-Myb and C/EBP-α[63], c-Jun and c-Fos [40].”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [40]
The transactivation domain of PU.1 (amino acids 1-118) is necessary for basal transactivation of the M-CSF receptor promoter by PU.1.
“The transactivation domain of PU.1 (amino acids 1–118) is necessary for the basal transactivation of the M-CSF receptor promoter by PU.1.”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [40]
c-Jun binds PU.1 at the β3/β4 region of its ETS domain and activates it independently of JNK phosphorylation, acting as a JNK-independent co-activator.
“Because c-Jun physically binds to PU.1 at the β3/β4 region of its ETS domain and functionally activates it independently of JNK phosphorylation, it was concluded that c-Jun acts as a JNK-independent co-activator of PU.1 (Fig. 3).”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [40]
GATA-1 represses the transcriptional activity of PU.1 by blocking the binding of its co-activator c-Jun to the β3/β4 region in its DNA-binding domain.
“On the contrary, GATA-1 represses the transcriptional activity of PU.1 by blocking the binding of its co-activator c-Jun to the β3/β4 region in its DNA-binding domain [40, 65] (Fig. 5).”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [40]
The β3/β4 region (amino acids 243-254) of PU.1 in the Ets domain interacts with c-Jun, which acts as a critical coactivator of PU.1 transactivation of myeloid promoters.
“We recently have demonstrated that the β3/β4 region (amino acids 243–254) of PU.1 in the Ets domain interacts with a number of proteins (N.W.-a., Y. Koyama, G.B., S. Tetradis, J. Tsukada, Y.-T. Ro, D.G.T., and P.E.A., unpublished results), including c-Jun, which acts as a critical coactivator of PU.1 transactivation of myeloid promoters (20).”
From Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1 (1999) · cites this paper as [20]
AML-1B, C/EBPα, and c-Jun interact with the β3/β4 region of PU.1 and synergize with PU.1 to activate downstream myeloid genes.
“AML-1B (19), C/EBPα (46), and c-Jun (20) all interact with the β3/β4 region of PU.1 and synergize with PU.1 to activate downstream myeloid genes.”
From Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1 (1999) · cites this paper as [20]
PU.1 cannot transactivate the M-CSF receptor in F9 cells unless c-Jun is cotransfected.
“PU.1 cannot transactivate the M-CSF receptor in F9 cells, which do not express endogenous c-Jun, unless c-Jun is cotransfected into these cells (20).”
From Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1 (1999) · cites this paper as [20]
c-Jun and GATA-1 each bind specifically to the PU.1 DNA-binding domain.
“Both c-Jun and GATA-1 can bind specifically to the PU.1 DNA-binding domain individually (Figs. 1 and 2; ref. 20).”
From Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1 (1999) · cites this paper as [20]
c-Jun interacts with the β3/β4 region of PU.1 and enhances PU.1 transactivation of myeloid target promoters such as the M-CSF receptor.
“We have shown recently that the human protooncogene, c-Jun, interacts with the β3/β4 region of PU.1 and enhances the ability of PU.1 to transactivate myeloid target promoters such as the M-CSF receptor (20).”
From Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1 (1999) · cites this paper as [20]
c-Jun strongly binds to PU.1.
“We already demonstrated that c-Jun strongly binds to PU.1, 23 and here we show that C/EBP␣ also binds to PU.1 strongly.”
From Granulocyte inducer C/EBPα inactivates the myeloid master regulator PU.1: possible role in lineage commitment decisions (2002) · cites this paper as [23]
Cotransfection of c-Jun with PU.1 results in approximately 40-fold synergy on p(PU.1)4TK.
“When cotransfected with the expression plasmid of c-Jun, we observed a strong synergy of approximately 40-fold, as described before.23”
From Granulocyte inducer C/EBPα inactivates the myeloid master regulator PU.1: possible role in lineage commitment decisions (2002) · cites this paper as [23]
c-Jun acts as a PU.1 coactivator, boosts M-CSF receptor expression, and participates in monocyte lineage development.
“c-Jun has been shown to be a coactivator of PU.1, resulting in increased macrophage-colony-stimulating factor (M-CSF) receptor expression, and it is involved in the development of the monocyte lineage.23”
From Granulocyte inducer C/EBPα inactivates the myeloid master regulator PU.1: possible role in lineage commitment decisions (2002) · cites this paper as [23]
c-Jun is a JNK-independent coactivator of PU.1 that physically interacts with PU.1 in the β3-β4 region of the DNA-binding domain, resulting in increased M-CSF receptor expression.
“We showed earlier that the transcription factor c-Jun is a JNK-independent coactivator of PU.1 and that it physically interacts with PU.1 in the 3-4 region of the DNA-binding domain, resulting in increased M-CSF receptor expression.23”
From Granulocyte inducer C/EBPα inactivates the myeloid master regulator PU.1: possible role in lineage commitment decisions (2002) · cites this paper as [23]
c-Jun can function as a coactivator of the PU.1 transcription factor, which is important for the monocytic lineage.
“Moreover, c-Jun can also function as a coactivator of the PU.1 transcription factor, which is important for the monocytic lineage (5).”
From Downregulation of c-Jun Expression by Transcription Factor C/EBPα Is Critical for Granulocytic Lineage Commitment (2002) · cites this paper as [5]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Conflicting boundaries for the c-Jun transactivation domain
MinorThe results identify amino acids 1-87 as the c-Jun transactivation domain, while the Fig. 3 caption identifies amino acids 1-251 as that domain.
“The transactivation domain of c-Jun (amino acids 1-87);”
“depicting the transactivation domain (amino acids 1-251), basic domain (BD, amino acids 251-281), and the leucine zipper (LZ, amino acids 281-313).”
AP-1 competitor is incorrectly called self-unlabeled for M-CSF receptor probe lanes
MinorThe caption says lanes 7-14 use an M-CSF receptor promoter probe, but calls the AP-1 probe added in lanes 11 and 14 a self-unlabeled competitor. An AP-1 probe is not an unlabeled version of the M-CSF receptor probe.
“In lanes 3, 6, 11, and 14, a 100-fold molar excess of self-unlabeled competitor (AP-1 probe) was added to the electrophoretic mobility shift assay.”
“in lanes 7-14, an M-CSF receptor promoter oligonucleotide extending from position bp Ϫ88 to ϩ71 with respect to the major transcription start site was used.”
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Cited by
Sorted by citations
Disruption of differentiation in human cancer: AML shows the way
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Self-citationTranscriptional control of granulocyte and monocyte development
Friedman, A. D. (2007) · Oncogene · doi:10.1038/sj.onc.1210764 · Cited by 427 · see citing works
“…promoters in the absence of an AP-1 cis element, and PU.1 and c-Jun cooperatively regulates the monocytic macrosialin and scavenger receptor promoters via distinct binding sites Oncogene (Moulton et al., 1994; Bassuk and Leiden, 1995; Li et al., 1998; Behre et al., 1999; Grondin et al., 2007).”
BackgroundPU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding
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“The bZIP family transcription factor, c-Jun, physically associates with and enhances the activity of Spi-1 on the CSF1R promoter (coding for M-CSF receptor) in the absence of direct DNA binding [116].”
BackgroundTranscriptional regulation of granulocyte and monocyte development
Friedman, A. D. (2002) · Oncogene · doi:10.1038/sj.onc.1205324 · Cited by 325 · see citing works
“…monocytic cells, the M-CSF Receptor promoter is activated synergistically by C/EBP, PU.1, and CBF (Zhang et al., 1994a,b, 1996a; Petrovick et al., 1998), and c-Jun activates the M-CSF receptor gene indirectly, via its ability to interact with PU.1 (Bassuk and Leiden, 1995; Behre et al., 1999a).”
Backgroundc-Jun, at the crossroad of the signaling network
Meng, Q., & Xia, Y. (2011) · Protein & Cell · doi:10.1007/s13238-011-1113-3 · Cited by 298 · see citing works
“…include c-Jun binding to the Ets domain of PU.1, directing the complex to the PU.1 binding site in the M-CSF receptor promoter for transcriptional activation (Behre et al., 1999), whereas, the c-Jun/MyoD complex is recruited to the MyoD promoter to inhibit myogenesis (Bengal et al., 1992).”
BackgroundThe single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination
Wimmers, F., Donato, M., Kuo, A. J., Ashuach, T., Gupta, S., Li, C., Dvorak, M., Foecke, M. H., Chang, S. E., Hagan, T., et al. (2021) · Cell · doi:10.1016/j.cell.2021.05.039 · Cited by 266 · see citing works
“While the role of AP-1 as a key regulator of differentiation, inflammation, and polarization in myeloid cells is well described (Behre et al., 1999; Van der Bruggen et al., 1999; Das et al., 2009; Fontana et al., 2015; Fujioka et al., 2004; Hannemann et al., 2017; Monick et al., 1999; Phanstiel et al., 2017; Tsai et a…”
BackgroundBiological Roles of Neutrophil-Derived Granule Proteins and Cytokines
Cassatella, M. A., Tarasova, N. K., Tamassia, N., & Soehnlein, O. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.05.003 · Cited by 247 · see citing works
MOLECULAR GENETICS OF T CELL DEVELOPMENT
Rothenberg, E. V., & Taghon, T. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115737 · Cited by 256 · see citing works
Transcriptional Regulation of CHI3L1, a Marker Gene for Late Stages of Macrophage Differentiation
Rehli, M., Niller, H. H., Ammon, C., Langmann, S., Schwarzfischer, L., Andreesen, R., & Krause, S. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306792200 · Cited by 249 · see citing works
Vangala, R. K., Heiss-Neumann, M. S., Rangatia, J. S., Singh, S. M., Schoch, C., Tenen, D. G., Hiddemann, W., & Behre, G. (2003) · Blood · doi:10.1182/blood-2002-04-1288 · Cited by 245 · see citing works
Self-citationHeterozygous PU.1 mutations are associated with acute myeloid leukemia
Mueller, B. U., Pabst, T., Osato, M., Asou, N., Johansen, L. M., Minden, M. D., Behre, G., Hiddemann, W., Ito, Y., & Tenen, D. G. (2002) · Blood · doi:10.1182/blood.v100.3.998 · Cited by 243 · see citing works
“[35]S-methionine–labeled proteins were prepared using 1 g of plasmid DNA as template for coupled in vitro transcriptiontranslation (TNT; Promega, Madison, WI).”
MethodSelf-citationPassegue, E. A., Jochum, W., Schorpp‐Kistner, M., Möhle-Steinlein, U., & Wagner, E. F. (2001) · Cell · doi:10.1016/s0092-8674(01)00188-x · Cited by 236 · see citing works
Regulation of Ets function by protein–protein interactions
Li, R., Pei, H., & Watson, D. K. (2000) · Oncogene · doi:10.1038/sj.onc.1204035 · Cited by 229 · see citing works
“PU.1 also tethers the bZIP transcription factor c-Jun, via interacting of ETS domain of PU.1 with basic domain of Jun, to enhance the transcriptional activity of the promoter of the M-CSF receptor gene (Behre et al., 1999).”
BackgroundNagy, L., Szántó, A., Szatmári, I., & Széles, L. (2012) · Physiological Reviews · doi:10.1152/physrev.00004.2011 · Cited by 215 · see citing works
Essential role of Jun family transcription factors in PU.1 knockdown–induced leukemic stem cells
Steidl, U., Rosenbauer, F., Verhaak, R. G. W., Gu, X., Ebralidze, A., Otu, H. H., Klippel, S., Steidl, C., Bruns, I., Costa, D. B., et al. (2006) · Nature Genetics · doi:10.1038/ng1898 · Cited by 184 · see citing works
“1 with regard to transcriptional activation of the M-CSF receptor promoter and, hence, induction of monocytic differentiatio”
BackgroundSelf-citationThe role of PU.1 and GATA-1 transcription factors during normal and leukemogenic hematopoiesis
Burda, P., Laslo, P., & Stopka, T. (2010) · Leukemia · doi:10.1038/leu.2010.104 · Cited by 184 · see citing works
Anderson, M. K., Weiss, A. H., Hernandez-Hoyos, G., Dionne, C. J., & Rothenberg, E. V. (2002) · Immunity · doi:10.1016/s1074-7613(02)00277-7 · Cited by 182 · see citing works
The in vivo profile of transcription factors during neutrophil differentiation in human bone marrow
Bjerregaard, M. D., Jurlander, J., Klausen, P. H., Borregaard, N., & Cowland, J. B. (2003) · Blood · doi:10.1182/blood-2002-03-0835 · Cited by 178 · see citing works
Potential Autoregulation of Transcription Factor PU.1 by an Upstream Regulatory Element
Okuno, Y., Huang, G., Rosenbauer, F., Evans, E. K., Radomska, H. S., Iwasaki, H., Akashi, K., Moreau-Gachelin, F., Li, Y., Zhang, P., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.7.2832-2845.2005 · Cited by 174 · see citing works
“1 controls gene expression by interacting with many factors such as c-Jun (7), IRF4/Pip (14, 46, 47), NF-interleukin 6 beta (IL-6 ) (C/EBP ) (36), C/EBP (51), and GATA-1 (38, 52, 66, 67).”
Self-citationNiche signals and transcription factors involved in tissue-resident macrophage development
T’Jonck, W., Guilliams, M., & Bonnardel, J. (2018) · Cellular Immunology · doi:10.1016/j.cellimm.2018.02.005 · Cited by 165 · see citing works
LPS activation of Toll-like receptor 4 signals CD11b/CD18 expression in neutrophils
Zhou, X., Gao, X.-P., Fan, J., Liu, Q., Anwar, K. N., Frey, R. S., & Malik, A. B. (2004) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00327.2004 · Cited by 167 · see citing works
“1 DNA binding sites (2, 13) and the transcription factor c-Jun activated by JNK associates with the Ets domain of PU.”
Lécuyer, É. (2002) · Blood · doi:10.1182/blood-2002-02-0568 · Cited by 165 · see citing works
Wang, X., Scott, E., Sawyers, C. L., & Friedman, A. D. (1999) · Blood · doi:10.1182/blood.v94.2.560 · Cited by 166 · see citing works
Reddy, V. A., Iwama, A., Iotzova, G., Schulz, M., Elsasser, A., Vangala, R. K., Tenen, D. G., Hiddemann, W., & Behre, G. (2002) · Blood · doi:10.1182/blood.v100.2.483 · Cited by 152 · see citing works
Self-citationRosmarin, A. G., Yang, Z., & Resendes, K. K. (2005) · Experimental Hematology · doi:10.1016/j.exphem.2004.08.015 · Cited by 142 · see citing works
“1 and c-Jun physically interact via their DNA binding domains and cooperate to activate gene transcription [93].”
BackgroundWhen Ets transcription factors meet their partners
Verger, A., & Duterque‐Coquillaud, M. (2002) · BioEssays · doi:10.1002/bies.10068 · Cited by 134 · see citing works
Regulation of granulopoiesis by transcription factors and cytokine signals
Ward, A. C., Loeb, D., Soede-Bobok, A. A., Touw, I., & Friedman, A. (2000) · Leukemia · doi:10.1038/sj.leu.2401808 · Cited by 131 · see citing works
c-Jun and Hypoxia-Inducible Factor 1 Functionally Cooperate in Hypoxia-Induced Gene Transcription
Alfranca, A., Gutiérrez, M. D. C., Vara, A., Aragonés, J., Vidal, F., & Landázuri, M. O. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.1.12-22.2002 · Cited by 121 · see citing works
“1 and Sp1, respectively, without binding to DNA (6, 25).”
BackgroundIwama, A., Osawa, M., Hirasawa, R., Uchiyama, N., Kaneko, S., Onodera, M., Shibuya, K., Shibuya, A., Vinson, C., Tenen, D. G., et al. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011465 · Cited by 107 · see citing works
Self-citationMathas, S., Kreher, S., Meaburn, K. J., Jöhrens, K., Lamprecht, B., Assaf, C., Sterry, W., Kadin, M. E., Daibata, M., Joos, S., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900912106 · Cited by 102 · see citing works
“As expected because of the reciprocal t(2;5), NPM1-ALK (5q35–2p23), CSF1R-FRA2 (5q33.”
BackgroundInfluentialRegulation of human neutrophil granule protein expression
Borregaard, N., Theilgaard‐Mönch, K., Sørensen, O. E., & Cowland, J. B. (2001) · Current Opinion in Hematology · doi:10.1097/00062752-200101000-00005 · Cited by 103 · see citing works
Krysinska, H., Hoogenkamp, M., Ingram, R., Wilson, N., Tagoh, H., Laslo, P., Singh, H., & Bonifer, C. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01915-06 · Cited by 102 · see citing works
“1-mediated c-fms activity in transient-transfection assays (1).”
PU.1 and pRB Interact and Cooperate To Repress GATA-1 and Block Erythroid Differentiation
Rekhtman, N., Choe, K. S., Matushansky, I., Murray, S., Stopka, T., & Skoultchi, A. I. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.21.7460-7474.2003 · Cited by 102 · see citing works
“Both proteins also engage in specific interactions with other proteins that enhance their transcriptional activity, including PU.1 with c-Jun in myeloid cells ( 2 ) and with PU.1 interacting partner (Pip) in B cells (12) and GATA-1 with Friend of GATA-1 (FOG-1) in erythroid cells (60).”
BackgroundThe Transcriptional Repressor GFI-1 Antagonizes PU.1 Activity through Protein-Protein Interaction
Dahl, R. E., Iyer, S. R., Owens, K., Cuylear, D. D., & Simon, M. C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607613200 · Cited by 93 · see citing works
Takeda, M., Kato, H., Takamiya, A., Yoshida, A., & Kiyama, H. (2000) · PubMed · Cited by 94 · see citing works
NF-IL6 (C/EBPβ) Vigorously Activates il1b Gene Expression via a Spi-1 (PU.1) Protein-Protein Tether
Yang, Z., Wara-aswapati, N., Chen, C., Tsukada, J., & Auron, P. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000145200 · Cited by 92 · see citing works
Behre, G., Singh, S. M., Liu, H., Bortolin, L. T., Christopeit, M., Radomska, H. S., Rangatia, J., Hiddemann, W., Friedman, A. D., & Tenen, D. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202301200 · Cited by 81 · see citing works
“(Behre et al., 1999; Behre et al., 1997)”
BackgroundMethodSelf-citationCoghlan, M. P., Chou, M. M., & Carpenter, C. L. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.8.2880-2889.2000 · Cited by 84 · see citing works
“The L61 Ras construct has been previously described (4).”
BackgroundSelf-citationWang, J.-M., Lai, M.-Z., & Yang-Yen, H.-F. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.6.1896-1909.2003 · Cited by 83 · see citing works
“PU.1 was shown to interact with many transcription factors or coactivators, including NF-EM5, Ets-1, NF-IL-6, HMG-I(Y), c-Jun, IRF-1, ICSBP, AML1, and CBP (2, 8, 25, 33, 35, 36, 51, 52).”
BackgroundChen, S.-Y., Cai, C., Fisher, C. J., Zheng, Z., Omwancha, J., Hsieh, C.-L., & Shemshedini, L. (2006) · Oncogene · doi:10.1038/sj.onc.1209705 · Cited by 77 · see citing works
“Interestingly, at least with regard to AR (Wise et al., 1998), PU.1 (Behre et al., 1999), and ETV1 (C Cai and L Shemshedini, unpublished results), c-Jun’s function as a coactivator is separable from its transactivation function, as the c-Jun(Ala63/73) mutant is deficient in transactivation but fully active in coactiva…”
BackgroundCeccarelli, V., Racanicchi, S., Martelli, M. P., Nocentini, G., Fettucciari, K., Riccardi, C., Marconi, P., Nardo, P. D., Grignani, F., Binaglia, L., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.253609 · Cited by 78 · see citing works
Gupta, P., Gurudutta, G. U., Saluja, D., & Tripathi, R. P. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00757.x · Cited by 74 · see citing works
“1 has been shown to cooperate with NF-IL6 (C/EBP- ) [43], c-Myb and C/EBP- [63], c-Jun and c-Fos [40].”
BackgroundPU.1/Interferon Regulatory Factor Interactions; Mechanisms of Transcriptional Regulation
Marecki, S., & Fenton, M. J. (2000) · Cell Biochemistry and Biophysics · doi:10.1385/cbb:33:2:127 · Cited by 74 · see citing works
The MADS transcription factor Mef2c is a pivotal modulator of myeloid cell fate
Schüler, A., Schwieger, M., Engelmann, A., Riecken, K., Horn, S., Müller, U., Arnold, M., Olson, E. N., & Stocking, C. (2008) · Blood · doi:10.1182/blood-2007-10-116343 · Cited by 67 · see citing works
EVI1 Impairs Myelopoiesis by Deregulation of PU.1 Function
Laricchia‐Robbio, L., Premanand, K., Rinaldi, C. R., & Nucifora, G. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2562 · Cited by 74 · see citing works
“Top left, HA-EVI1, HA-EVI1(1-283), and HA-EVI1(159-283) interact with PU.”
BackgroundMethodInfluentialRole of Transcription Factors C/EBPa and PU.1 in Normal Hematopoiesis and Leukemia
Koschmieder, S., Rosenbauer, F., Steidl, U., Owens, B. M., & Tenen, D. G. (2005) · International Journal of Hematology · doi:10.1532/ijh97.05051 · Cited by 72 · see citing works
“C-Jun does not bind DNA directly but acts by association of its basic domain with the ETS-domain of PU.1 [ 37 ].”
BackgroundSelf-citationSchuringa, J. J., Timmer, H., Luttickhuizen, D., Vellenga, E., & Kruijer, W. (2001) · Cytokine · doi:10.1006/cyto.2001.0856 · Cited by 70 · see citing works
Review: The Role of IRF-4 in Transcriptional Regulation
Marecki, S., & Fenton, M. J. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/107999002753452737 · Cited by 67 · see citing works
Kihara-Negishi, F., Yamamoto, H., Suzuki, M., Yamada, T., Sakurai, T., Tamura, T., & Oikawa, T. (2001) · Oncogene · doi:10.1038/sj.onc.1204756 · Cited by 65 · see citing works
“AML1, GATA-1, and Jun family transcription factors also interact with the Ets domain of PU.1 (Behre et al., 1999; Zhang et al., 1999).”
BackgroundTailoring Ras-pathway—Inhibitor combinations for cancer therapy
Blum, R., & Kloog, Y. (2005) · Drug Resistance Updates · doi:10.1016/j.drup.2005.11.002 · Cited by 64 · see citing works
“The PI3-K pathway, for example, is activated by both Ras-dependent and Ras-independent mechanisms (Besset et al., 2000; Khwaja et al., 1998; Potempa and Ridley, 1998; Rodriguez Viciana et al., 1997; Takeda et al., 1999).”
Transcription factor PU.1 is expressed in white adipose and inhibits adipocyte differentiation
Wang, F., & Tong, Q. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00422.2007 · Cited by 63 · see citing works
“1 was reported to interact with other transcription factors, such as GATA-1, GATA-2 (48), C/EBP (32), and c-Jun (1).”
Backgroundc-Jun Homodimers Can Function as a Context-Specific Coactivator
Grondin, B., Lefrançois, M., Tremblay, M., Saint-denis, M., Haman, A., Waga, K., Bédard, A., Tenen, D., & Hoang, T. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00936-06 · Cited by 66 · see citing works
“myelomonocytic genes (6, 32, 40, 42, 64) and plays essential roles in the development of myeloid and lymphoid cells (13, 28, 48, 52, 68).”
BackgroundSelf-citationRojo, R., Pridans, C., Langlais, D., & Hume, D. A. (2017) · Clinical Science · doi:10.1042/cs20170238 · Cited by 60 · see citing works
Disabled‐2 is transcriptionally regulated by ICSBP and augments macrophage spreading and adhesion
Rosenbauer, F., Kallies, A., Scheller, M., Knobeloch, K., Rock, C. O., Schwieger, M., Stocking, C., & Horak, I. D. (2002) · The EMBO Journal · doi:10.1093/emboj/21.3.211 · Cited by 64 · see citing works
Shen, C., Chen, M.-T., Zhang, X.-H., Yin, X.-L., Ning, H.-M., Su, R., Lin, H.-S., Song, L., Wang, F., Ma, Y.-N., et al. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1006259 · Cited by 62 · see citing works
“1 [47] Similarly, GATA2, which can be transcriptionally activated by MECOM [27], is able to interfere with the interaction between c-Jun and PU.”
BackgroundRetractedBSAP Can Repress Enhancer Activity by Targeting PU.1 Function
Maitra, S., & Atchison, M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.6.1911-1922.2000 · Cited by 72 · see citing works
“The presence (1) or absence (2) of CMV-BSAP is indicated above the lanes.”
BackgroundFoster, N. M., Lea, S., Preshaw, P. M., & Taylor, J. J. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0206086 · Cited by 61 · see citing works
“Furthermore, c-Jun, which has autonomous, transcriptional activity and activity as part of the activator protein 1 complex [35], has also been shown to synergize with PU.1 for upregulation of M-CSFR [ 36 ].”
BackgroundOh, I., Lau, A., & Eaves, C. J. (2000) · Blood · doi:10.1182/blood.v96.13.4160 · Cited by 63 · see citing works
Liew, C. W., Rand, K. D., Simpson, R. J. Y., Yung, W. W., Mansfield, R. E., Crossley, M., Proetorius-Ibba, M., Nerlov, C., Poulsen, F. M., & Mackay, J. P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602830200 · Cited by 62 · see citing works
Rangatia, J., Vangala, R. K., Singh, S. M., Peer Zada, A. A., Elsässer, A., Kohlmann, A., Haferlach, T., Tenen, D. G., Hiddemann, W., & Behre, G. (2003) · Oncogene · doi:10.1038/sj.onc.1206664 · Cited by 62 · see citing works
“C/EBPa interaction (Truong et al., 2003), but also as a driving force in the context of lineage commitment and normal differentiation, such as PU.1–c-Jun interaction (Behre et al., 1999), PU.1–”
BackgroundSelf-citationRangatia, J., Vangala, R. K., Treiber, N., Zhang, P., Radomska, H., Tenen, D. G., Hiddemann, W., & Behre, G. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.24.8681-8694.2002 · Cited by 62 · see citing works
“1 transcription factor, which is important for the monocytic lineage (5).”
BackgroundMethodSelf-citationSubversion of T lineage commitment by PU.1 in a clonal cell line system
Dionne, C. J., Tse, K. Y., Weiss, A. H., Franco, C. B., Wiest, D. L., Anderson, M. K., & Rothenberg, E. V. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2005.01.027 · Cited by 54 · see citing works
An Effective Model of the Retinoic Acid Induced HL-60 Differentiation Program
Tasseff, R. A., Jensen, H. A., Congleton, J., Dai, D. L., Rogers, K. V., Sagar, A., Bunaciu, R. P., Yen, A., & Varner, J. D. (2017) · Scientific Reports · doi:10.1038/s41598-017-14523-5 · Cited by 54 · see citing works
Gangenahalli, G. U., Gupta, P., Saluja, D., Verma, Y. K., Kishore, V., Chandra, R., Sharma, R. K., & Ravindranath, T. (2005) · Stem Cells and Development · doi:10.1089/scd.2005.14.140 · Cited by 53 · see citing works
“…conserved ETS domain of approximately 85 amino acids, confined to the carboxyl terminus of PU.1, mediates binding to DNA as well as interaction with a number of other proteins such as c-Jun, GATA-1, GATA-2, CAAT/enhancer binding protein (cid:1) and (cid:2) (C/EBP) and AML1 (12–16) (Fig.”
Anderson, M. K., Sun, X. H., Miracle, A. L., Litman, G. W., & Rothenberg, E. V. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.2.553 · Cited by 53 · see citing works
Verger, A., Buisine, E., Carrère‐Kremer, S., Wintjens, R. T., Flourens, A., Coll, J., Stéhelin, D., & Duterque‐Coquillaud, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010208200 · Cited by 50 · see citing works
Matsumura, I., Kawasaki, A., Tanaka, H., Sonoyama, J., Ezoe, S., Minegishi, N., Nakajima, K., Yamamoto, M., & Kanakura, Y. (2000) · Blood · doi:10.1182/blood.v96.7.2440 · Cited by 53 · see citing works
Targeting JNK pathway promotes human hematopoietic stem cell expansion
Xiao, X., Lai, W., Xie, H., Liu, Y., Guo, W., Liu, Y., Yu, L., Li, Y., Zhang, J. S., Chen, W., et al. (2019) · Cell Discovery · doi:10.1038/s41421-018-0072-8 · Cited by 50 · see citing works
Zada, A. A. P., Singh, S. M., Reddy, V. A., Elsässer, A., Meisel, A., Haferlach, T., Tenen, D. G., Hiddemann, W., & Behre, G. (2003) · Oncogene · doi:10.1038/sj.onc.1206393 · Cited by 51 · see citing works
“We focused our attention on c-Jun, since it is implicated in the regulation of cell proliferation and cell cycle progression (Kovary and Bravo, 1991; Smith and Prochownik, 1992; Behre et al., 1999; Schreiber et al., 1999; Wisdom et al., 1999; Bakiri et al., 2000; Shaulian and Karin, 2001).”
BackgroundMethodInfluentialSelf-citationKöffel, R., Meshcheryakova, A., Warszawska, J. M., Hennig, A., Wagner, K., Jörgl, A., Gubi, D., Moser, D., Hladik, A., Hoffmann, U., et al. (2014) · Blood · doi:10.1182/blood-2014-07-588178 · Cited by 49 · see citing works
Development of macrophages of cyprinid fish
Hanington, P. C., Tam, J., Katzenback, B. A., Hitchen, S. J., Barreda, D. R., & Belosevic, M. (2008) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2008.11.004 · Cited by 48 · see citing works
“1 has been shown to cooperatewith NF-IL6b (C/EBPd) [121], cMyb and C/EBPa [122], c-Jun and c-Fos [123– 125], and Ets-1 [126].”
BackgroundSchnurri-3 (KRC) Interacts with c-Jun to Regulate the IL-2 Gene in T Cells
Oukka, M., Wein, M. N., & Glimcher, L. H. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20030421 · Cited by 49 · see citing works
PU.1-c-Jun interaction is crucial for PU.1 function in myeloid development
Zhao, X., Bartholdy, B., Yamamoto, Y., Evans, E. K., Alberich-Jordà, M., Staber, P. B., Benoukraf, T., Zhang, P., Zhang, J., Trinh, B. Q., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03888-7 · Cited by 46 · see citing works
Self-citationCooper, C. D. O., Newman, J. A., & Gileadi, O. (2014) · Biochemical Society Transactions · doi:10.1042/bst20130227 · Cited by 42 · see citing works
Elsässer, A., Franzen, M., Kohlmann, A., Weisser, M., Schnittger, S., Schoch, C., Reddy, V. A., Burel, S., Zhang, D., Ueffing, M., et al. (2003) · Oncogene · doi:10.1038/sj.onc.1206673 · Cited by 47 · see citing works
“Mouse c-jun in pSP65 for in vitro translation has been described (Behre et al., 1999b).”
MethodSelf-citationRole of activator protein-1 in the down-regulation of the human CYP2J2 gene in hypoxia
Marden, N. Y., Fiala‐Beer, E., Xiang, S.-H., et al. (2003) · Biochemical Journal · doi:10.1042/bj20021903 · Cited by 47 · see citing works
“1 [44], GATA-2 [45], and GATA-4 [46].”
Concise Review: Erythroid Versus Myeloid Lineage Commitment: Regulating the Master Regulators
Wolff, L., & Humeniuk, R. (2013) · Stem Cells · doi:10.1002/stem.1379 · Cited by 42 · see citing works
Kido, S., Inoue, D., Hiura, K., Wilde, J., Ito, Y., & Matsumoto, T. (2003) · Bone · doi:10.1016/s8756-3282(03)00049-8 · Cited by 44 · see citing works
“Previous studies have identified DNA elements that confer responses to AP-1 and/or VDR in other macrophage/osteoclast lineage-associated genes induced upon HL60 cell differentiation, including carbonic anhydrase II [38], MMP-9 [39], and c-fms [40].”
BackgroundGeng, C.-D., & Vedeckis, W. V. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508245200 · Cited by 43 · see citing works
Activating PTPN11 mutants promote hematopoietic progenitor cell-cycle progression and survival
Yang, Z., Li, Y., Yin, F., & Chan, R. J. (2008) · Experimental Hematology · doi:10.1016/j.exphem.2008.04.016 · Cited by 41 · see citing works
“1 to enhance monocytic differentiation [72,73].”
Cytomegalovirus IE2 Protein Stimulates Interleukin 1β Gene Transcription via Tethering to Spi-1/PU.1
Wara-aswapati, N., Yang, Z., Waterman, W. R., Koyama, Y., Tetradis, S., Choy, B. K., Webb, A. C., & Auron, P. E. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.10.6803 · Cited by 41 · see citing works
“Based on this evidence, we propose a protein-tethered transactivation (PTT) mechanism of il1b by IE2 in which the Spi-1 wHTH directly binds to the il1b promoter and tethers IE2 protein, which is unable to directly bind the promoter, providing a multifunctional TAD required for gene expression.”
BackgroundInfluentialShimohashi, N., Nakamuta, M., Uchimura, K., Sugimoto, R., Iwamoto, H., Enjoji, M., & Nawata, H. (2000) · Journal of Cellular Biochemistry · doi:10.1002/1097-4644(20000915)78:4 · Cited by 54 · see citing works
Ishikawa, Y., Nakayama, K., Morimoto, M., Mizutani, A., Nakayama, A., Toyoshima, K., Hayashi, A., Takagi, S., Dairiki, R., Miyashita, H., et al. (2017) · Oncogenesis · doi:10.1038/oncsis.2017.76 · Cited by 41 · see citing works
Transcriptional regulation of hemopoiesis
Barreda, D. R., & Belosevic, M. (2001) · Developmental & Comparative Immunology · doi:10.1016/s0145-305x(01)00035-0 · Cited by 40 · see citing works
Elements of transcription factor network design for T-lineage specification.
Rothenberg, E., & Anderson, M. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0667 · Cited by 48 · see citing works
Cai, C., Hsieh, C.-L., & Shemshedini, L. (2007) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-06-0430 · Cited by 39 · see citing works
“First, the AP-1 site on MMP-1 was mutated to yield the reporter MMP1(mAP1)-Luc (25).”
BackgroundInfluentialColin, L., Vandenhoudt, N., de Walque, S., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019084 · Cited by 36 · see citing works
Rosenbauer, F., Wagner, K., Zhang, P., Knobeloch, K., Iwama, A., & Tenen, D. (2004) · Blood · doi:10.1182/blood-2003-08-2688 · Cited by 34 · see citing works
Self-citationOmwancha, J., Zhou, X., Chen, S., Baslan, T., Fisher, C. J., Zheng, Z., Cai, C., & Shemshedini, L. (2006) · Endocrine · doi:10.1385/endo:29:2:363 · Cited by 34 · see citing works
PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding
Zhang, P., Zhang, X., Iwama, A., et al. (2000) · Blood · doi:10.1182/blood.v96.8.2641.h8002641_2641_2648 · Cited by 34 · see citing works
Self-citationT-lineage specification and commitment: a gene regulation perspective
Rothenberg, E. V. (2002) · Seminars in Immunology · doi:10.1016/s1044532302000787 · Cited by 34 · see citing works
PU.1 binding to the p53 family of tumor suppressors impairs their transcriptional activity
Tschan, M. P., Reddy, V. A., Ress, A., Arvidsson, G., Fey, M. F., & Torbett, B. E. (2008) · Oncogene · doi:10.1038/sj.onc.1211004 · Cited by 31 · see citing works
“1 coactivator (Behre et al., 1999).”
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- Authors
- Behre, G., Whitmarsh, A. J., Coghlan, M. P., Hoang, T., Carpenter, C. L., Zhang, D.-E., Davis, R. J., & Tenen, D. G.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- University of Massachusetts Chan Medical School (US)
- Montreal Clinical Research Institute (CA)
- Corresponding author
- Tenen, Daniel G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-02
- Volume
- 274
- Issue
- 8
- Pages
- 4939-4946
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2053208432
- Semantic Scholar
- 4e998b4c3512ed89215167ef141aaf971f60dbb5
- Cited by
- 183
- References
- 69
- Citations by year
- 2026: 5 · 2025: 2 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 8 · 2016: 5 · 2015: 1 · 2014: 5 · 2013: 4 · 2012: 1
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- c-Jun, PU.1, transcriptional coactivation, M-CSF receptor, monocyte differentiation, AP-1, c-Jun NH2-terminal kinase, Ras signaling
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Haplorhini, Base Sequence, Binding Sites, Cell Differentiation, Cell Line, DNA, DNA-Binding Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
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