The transcription factor PU.1 is involved in macrophage proliferation.
Open accessAbstract
PU.1 is a tissue-specific transcription factor that is expressed in cells of the hematopoietic lineage including macrophages, granulocytes, and B lymphocytes. Bone marrow-derived macrophages transfected with an antisense PU.1 expression construct or treated with antisense oligonucleotides showed a decrease in proliferation compared with controls. In contrast, bone marrow macrophages transfected with a sense PU.1 expression construct displayed enhanced macrophage colony-stimulating factor (M-CSF)-dependent proliferation. Interestingly, there was no effect of sense or antisense constructs of PU.1 on the proliferation of the M-CSF-independent cell line, suggesting that the response was M-CSF dependent. This was further supported by the finding that macrophages transfected with a sense or an antisense PU.1 construct showed, respectively, an increased or a reduced level of surface expression of receptors for M-CSF. The enhancement of proliferation seems to be selective for PU.1, since transfections with several other members of the ets family, including ets-2 and fli-1, had no effect. Various mutants of PU.1 were also tested for their ability to affect macrophage proliferation. A reduction in macrophage proliferation was found when cells were transfected with a construct in which the DNA-binding domain of PU.1 was expressed. The PEST (proline-, glutamic acid-, serine-, and threonine-rich region) sequence of the PU.1 protein, which is an important domain for protein-protein interactions in B cells, was found to have no influence on PU.1-enhanced macrophage proliferation when an expression construct containing PU.1 minus the PEST domain was transfected into bone marrow-derived macrophages. In vivo, PU.1 is phosphorylated on several serine residues. The transfection of plasmids containing PU.1 with mutations at each of five serines showed that only positions 41 and 45 are critical for enhanced macrophage proliferation. We conclude that PU.1 is necessary for the M-CSF-dependent proliferation of macrophages. One of the proliferation-relevant targets of this transcription factor could be the M-CSF receptor.
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Written from the paper’s full text.
TL;DR
PU.1 is required for M-CSF-dependent macrophage proliferation: antisense PU.1 reduced proliferation, while sense PU.1 enhanced M-CSF- and GM-CSF-dependent proliferation. The effect appears linked to M-CSF receptor surface expression and requires PU.1 serine residues 41 and/or 45.
Key findings
- Antisense PU.1 expression construct or antisense oligonucleotides decreased bone marrow-derived macrophage (BMDM) proliferation; at 600 or 1,200 U/ml M-CSF, antisense versus control differences were significant (P < 0.01).
- Sense PU.1 enhanced M-CSF-dependent proliferation and also GM-CSF-dependent proliferation; the GM-CSF effect was abolished by anti-M-CSF antibodies, and anti-M-CSF caused a 30% decrease in control-vector BMDM proliferation.
- PU.1 sense increased and PU.1 antisense reduced surface M-CSF receptor expression; ets-2 and fli-1 had no effect on M-CSF-dependent proliferation.
- PU.1 mutants showed that the PEST domain was dispensable, the DNA-binding domain reduced proliferation, and only serine positions 41 and 45 were critical for enhanced macrophage proliferation.
Methods
- BMDM were obtained from 6-week-old DBA/2 mice and cultured with M-CSF/L cell-conditioned medium; macrophage cell lines RAW264.7, IC-21, and BAC1 2F5-A were also used.
- Cells were transfected by electroporation with PU.1 sense, antisense, mutant, ets-2, or fli-1 constructs, or treated with antisense oligonucleotides; transfection efficiency was 7–12% as assessed with green fluorescent protein.
- Proliferation was measured by [3H]thymidine incorporation or Coulter counting; M-CSF receptor surface expression was measured by specific antibodies and flow cytometry; experiments were performed at least five times, in triplicate, with Student’s paired t test.
Limitations
- The paper states that the number of PU.1-regulated genes that could modulate macrophage proliferation in response to M-CSF is unknown.
- Evident from the text: transfection efficiency was only 7–12%, so proliferation and receptor data reflect effects in a minority of cells within mixed populations.
- Evident from the text: some supporting results are reported as “data not shown,” including proliferation of M-CSF-independent macrophage cell lines and receptor results with antisense oligonucleotides.
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- Findingown data§ Introduction
PU.1 expression construct stimulates GM-CSF-dependent proliferation of bone marrow macrophages.
“Transfection of a PU. 1 expression construct into bone marrow macrophages was found to stimulate both M- and GM-CSF-dependent pro- liferation of these cells, whereas transfection ofa PU.1 anti- sense construct or a construct that expressed DNA-binding domain of PU.1 into bone marrow macrophages was found to inhibit the proliferative effect of the growth factors.”
- Also stated in: § Results · plain
“When macrophages were transfected with an expression construct containing PU. 1, a significant increase in thymidine incorporation was observed only in cells treated with M-CSF or GM-CSF.”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data§ Summary
Mutations at serines 41 and 45 are critical for PU.1-enhanced macrophage proliferation.
“The transfection of plasmids containing PU.1 with mutations at each of five serines showed that only positions 41 and 45 are critical for enhanced macrophage proliferation.”
Quote in the paperSubstantial claim- Rests on an assumption: In vivo, PU.1 is phosphorylated on several serine residues.
- Findingown data§ Summary
A construct expressing the DNA-binding domain of PU.1 reduces macrophage proliferation.
“A reduction in mac- rophage proliferation was found when cells were transfected with a construct in which the DNA-binding domain of PU.1 was expressed.”
Quote in the paperSubstantial claim - Findingown data§ Summary
Bone marrow-derived macrophages transfected with an antisense PU.1 expression construct show decreased proliferation compared with controls.
“Bone marrow-derived macrophages transfected with an antisense PU.1 expression construct or treated with antisense oligonucle- otides showed a decrease in proliferation compared with controls.”
- Also stated in: § Results · plain
“BMDM transfected with the antisense PU.1 construct in the presense of M-CSF had a signifi- cantly reduced thymidine incorporation compared with the controls in which the vector alone was transfected into the cells (Fig. 1 A).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data§ Results
Transfection of PU.1 into BMDM in the absence of M-CSF has no effect on proliferation.
“Transfection of PU.1 into BMDM in the absence of M-CSF had no effect on the proliferation of the macro- phages, suggesting that the effect of the antisense and sense PU. 1 constructs was growth factor dependent.”
Quote in the paperSubstantial claim
- Findingown data§ Results
Treatment of bone marrow-derived macrophages with antisense oligonucleotides to PU.1 reduces their proliferation.
“We observed that the antisense but not the sense oligonucle- otide inhibited BMDM thymidine incorporation in a dose- dependent manner that was dependent on the concentra- tion of M-CSF in the media (Fig. 1 B).”
Quote in the paperSubstantial claim - Findingown data§ Summary
Transfection with other ets family members, including ets-2 and fli-1, has no effect on macrophage proliferation.
“The enhancement of proliferation seems to be selective for PU.1, since transfections with several other members of the ets family, including ets-2 and fli-1, had no effect.”
- Also stated in: § Results · plain
“When expression con- structs containing either ets-2 or fli-1 were transfected into BMDM, no increase in macrophage proliferation above that seen using the vector alone was detected (Fig. 6).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data§ Results
A PU.1 expression construct lacking the PEST domain enhances macrophage proliferation in BMDM similarly to wild-type PU.1.
“When a PU. 1 expression construct lacking the PEST do- main was transfected into BMDM, an enhancement of macrophage proliferation similar to that obtained using the wild PU. 1 construction was observed”
Quote in the paperSubstantial claim- Rests on an assumption: BMDM proliferation is a valid measure of macrophage proliferation.
- Rests on an assumption: The PU.1 constructs are expressed and function as intended in BMDM.
- Findingown data§ Results
In the presence of anti-M-CSF antibodies, GM-CSF does not stimulate thymidine incorporation above background in PU.1-transfected macrophages.
“We observed that in the presence of the mAb against M-CSF there was no stimulation ofthymidine incorporation above background when GM-CSF was added to the cultures and the PU.1 expression construct transfected into the cells (Fig. 4).”
Quote in the paperSubstantial claim - Findingown data§ Summary
Bone marrow macrophages transfected with a sense PU.1 expression construct display enhanced M-CSF-dependent proliferation.
“In contrast, bone marrow macrophages transfected with a sense PU.1 expression construct displayed enhanced macrophage colony- stimulating factor (M-CSF)-dependent proliferation.”
Quote in the paperSubstantial claim - Findingown data§ Summary
Macrophages transfected with an antisense PU.1 construct show reduced surface expression of M-CSF receptors.
“This was further supported by the finding that macrophages transfected with a sense or an antisense PU. 1 construct showed, respectively, an increased or a reduced level of surface expression of receptors for M-CSF.”
- Also stated in: § Results · plain
“In contrast, the BMDM transfected with the antisense PU.1 construct showed a re- duction of the same cell population (Fig. 6).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data§ Summary
Sense or antisense PU.1 constructs have no effect on the proliferation of M-CSF-independent cell lines.
“Interestingly, there was no effect of sense or antisense constructs of PU.1 on the proliferation of the M-CSF-independent cell line, suggesting that the response was M-CSF dependent.”
Quote in the paperSubstantial claim- Rests on an assumption: The macrophage cell lines IC-21, RAW264.7, and 2F5A express PU.1 endogenously.
- Rests on an assumption: The cell line used to test M-CSF independence is truly M-CSF-independent.
- Findingown data§ Summary
Macrophages transfected with a sense PU.1 construct show increased surface expression of M-CSF receptors.
“This was further supported by the finding that macrophages transfected with a sense or an antisense PU. 1 construct showed, respectively, an increased or a reduced level of surface expression of receptors for M-CSF.”
Quote in the paperSubstantial claim - Findingown data§ Results
PU.1 with the S132/133A or S148A mutations is as active as wild-type protein in stimulating proliferation of BMDM.
“PU.1 with the $132/133A or $148A mutations was as active as the wild-type protein in stimulating proliferation of BMDM (Fig. 7 B).”
Quote in the paperSubstantial claim- Rests on an assumption: The PU.1 constructs are expressed and function as intended in BMDM.
- Findingown data§ Results
Transfection of a PU.1 construct containing the DNA-binding domain (ETS domain) into BMDM decreases M-CSF-dependent proliferation.
“A decrease in M-CSF-dependent proliferation, however, was observed when a PU.1 construct containing the DNA- binding domain (ETS domain) was transfected into the cells (Fig. 7 B).”
- Also stated in: § Discussion · plain
“However, expression of the PU.1 DNA-binding domain resulted in a reduced proliferation of BMDM.”
Quote in the paperSubstantial claim- Rests on an assumption: BMDM proliferation is a valid measure of macrophage proliferation.
- Rests on an assumption: The PU.1 constructs are expressed and function as intended in BMDM.
- Also stated in: § Discussion · plain
- Findingown data§ Results
Anti-M-CSF antibodies cause a substantial decrease (30%) in BMDM proliferation in cells transfected with control vector alone.
“The addi- tion ofanti-M-CSF antibodies caused a substantial decrease (30%) in BMDM proliferation in cells transfected with con- trol vector alone.”
Quote in the paperSubstantial claim - Findingown data§ Discussion
In our experiments, ets-2 had no effect on M-CSF-dependent macrophage proliferation.
“In our experiments, ets-2 had no effect on M-CSF-dependent macrophage proliferation.”
Quote in the paperNot a substantial claim - Findingown data§ Discussion
The effect of PU.1 protein on proliferation seems to be specific because other ets family members such as ets-2 and fli-1 were ineffective in stimulating proliferation.
“The effect of PU.1 protein seems to be specific because other ets family members such as ets-2 and fli-1 were inef- fective in stimulating proliferation.”
Quote in the paperSubstantial claim - Findingown data§ Results
The effect of the S41/45A double mutation is about the same as either of the single mutations.
“The effect of the $41/45A double mutation was about the same as either of the single mutations.”
Quote in the paperNot a substantial claim- Rests on an assumption: Alanine substitution at serine 41 or 45 does not alter PU.1 function except by preventing phosphorylation.
- Rests on an assumption: The PU.1 constructs are expressed and function as intended in BMDM.
- Findingreasoning§ Discussion
PU.1 is not effective in cell lines whose proliferation is independent of growth factors.
“This may explain why PU.1 is not effective in cell lines whose proliferation is in- dependent of growth factors.”
Quote in the paperSubstantial claim - Interpretationown data§ Results
The enhancement of GM-CSF-dependent proliferation in PU.1-transfected macrophages may be related to autocrine production of M-CSF.
“These data suggest that the enhancement of GM- CSF-dependent proliferation in PU.l-transfected macro- phages may be related to the autocrine production of M-CSF (38-41).”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [38]
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- cites [39]
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- cites [40]
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- cites [41]
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- Interpretationown data§ Introduction
PU.1 is involved in macrophage proliferation.
“In the present study we demonstrate that PU.1 is in- volved in macrophage proliferation.”
- Also stated in: § Discussion · hedged
“The data presented here indicate that PU. 1 is involved in macrophage proliferation.”
Quote in the paperSubstantial claim- Rests on an assumption: The antisense and transfection experiments specifically modulate PU.1 activity without off-target effects.
- Rests on an assumption: BMDM proliferation is a valid measure of macrophage proliferation.
- Also stated in: § Discussion · hedged
- Interpretationown data§ Results
PU.1 is involved in a proliferative mechanism that is only present in growth factor-dependent macrophages.
“These data sug- gest that PU. 1 is involved in a proliferative mechanism that is only present in growth factor-dependent macrophages.”
Quote in the paperSubstantial claim - Interpretationown data§ Summary
The effect of PU.1 on macrophage proliferation is specific for PU.1.
“The enhancement of proliferation seems to be selective for PU.1, since transfections with several other members of the ets family, including ets-2 and fli-1, had no effect.”
- Also stated in: § Results · boosted
“Thus, we conclude that the effect of PU. 1 on macrophage proliferation is specific for PU.1.”
Quote in the paperSubstantial claim - Also stated in: § Results · boosted
- Interpretationreasoning§ Summary
The proliferative response to PU.1 sense or antisense constructs is M-CSF dependent.
“Interestingly, there was no effect of sense or antisense constructs of PU.1 on the proliferation of the M-CSF-independent cell line, suggesting that the response was M-CSF dependent.”
Quote in the paperSubstantial claim- Rests on an assumption: The cell line used to test M-CSF independence is truly M-CSF-independent.
- Interpretationown data§ Summary
PU.1 is necessary for the M-CSF-dependent proliferation of macrophages.
“We conclude that PU.1 is necessary for the M-CSF-dependent proliferation of macrophages.”
Quote in the paperSubstantial claim - Interpretationown data§ Results
The PEST domain is not important for PU.1's enhancement of macrophage proliferation.
“suggesting that the PEST domain was not important for this activity (Fig. 7 A).”
Quote in the paperSubstantial claim- Rests on an assumption: The PU.1 constructs are expressed and function as intended in BMDM.
- Interpretationown data§ Summary
One of the proliferation-relevant targets of PU.1 could be the M-CSF receptor.
“One of the proliferation-relevant targets of this transcription factor could be the M-CSF receptor.”
- Also stated in: § Results · boosted
“Thus, PU.1, which has been shown to bind the M-CSF promoter and regulate expression from this promoter using a reporter construct, is also involved in the regulation of M-CSF receptor expression in macro- phages in vivo.”
Quote in the paperSubstantial claim - Also stated in: § Results · boosted
- Interpretationown data§ Results
PU.1 is involved in the regulation of M-CSF receptor expression in macrophages in vivo.
“Thus, PU.1, which has been shown to bind the M-CSF promoter and regulate expression from this promoter using a reporter construct, is also involved in the regulation of M-CSF receptor expression in macro- phages in vivo.”
Quote in the paperSubstantial claim - Premisecitation§ Results
GM-CSF induces the expression of M-CSF.
“GM-CSF is known to induce the expression of M-CSF (38-41).”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [38]
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- cites [39]
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- cites [40]
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- cites [41]
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- Study design and conductown data§ Materials and Methods
Increasing the amount of DNA transfected in BMDM resulted in a concentration-dependent decrease in proliferation.
“We also found that increasing the amount of DNA transfected (any type) in BMDM resulted in a concentra- tion-dependent decrease in proliferation.”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Results
At least one functional activity of PU.1 in macrophages is related to the control of genes involved in M-CSF-stimulated cell proliferation.
“Taken together, these data support the hypothe- sis that at least one of the functional activities of PU. 1 in macrophages is related to the control of genes involved in M-CSF-stimulated cell proliferation.”
Quote in the paperSubstantial claim - Interpretationown data§ Results
PU.1 is involved in the regulation of macrophage proliferation that is M-CSF or GM-CSF dependent.
“These data suggest that PU.1 is involved in the regulation of macrophage proliferation that is M-CSF or GM-CSF dependent.”
- Also stated in: § Introduction · hedged
“Thus, PU.1 seems to regulate the expression of genes in- volved within macrophage proliferation.”
Quote in the paperSubstantial claim - Also stated in: § Introduction · hedged
- Interpretationown data§ Results
The effect of antisense and sense PU.1 constructs on macrophage proliferation is growth factor dependent.
“Transfection of PU.1 into BMDM in the absence of M-CSF had no effect on the proliferation of the macro- phages, suggesting that the effect of the antisense and sense PU. 1 constructs was growth factor dependent.”
Quote in the paperSubstantial claim - Premisecitation§ Discussion
A reduction in the expression of PU.1 coincides with recommitment to the program of erythroid differentiation and the loss of immortality.
“A reduction in the expression of PU.1 coincides with recommitment to the program of erythroid 66 PU.1 Is Involved in Macrophage Proliferation differentiation and the loss of immortality (47).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [47]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationown data§ Discussion
The region around serine 41 plays an important role in the macrophage proliferation activity of PU.1.
“The finding that mutations at serine 41 and 41/45 caused a lowering of proliferation in BMDM sug- gests that this region plays an important role for this activity.”
Quote in the paperSubstantial claim- Rests on an assumption: Alanine substitution at serine 41 or 45 does not alter PU.1 function except by preventing phosphorylation.
- Interpretationown data§ Discussion
PU.1 plays a critical role in the proliferation of macrophages.
“The block in macrophage prolif- eration using either an antisense PU. 1 expression construct or antisense oligonucleotides suggests that PU.1 plays a critical role in the proliferation of macrophages.”
Quote in the paperSubstantial claim- Rests on an assumption: The antisense and transfection experiments specifically modulate PU.1 activity without off-target effects.
- Rests on an assumption: BMDM proliferation is a valid measure of macrophage proliferation.
- Premisecitation§ Discussion
PU.1 directs the expression of the M-CSF receptor.
“Recently, it has been reported that PU.1 directs the expression of the M-CSF receptor (17, 42, 53).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [17]
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- cites [42]
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- cites [53]
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- Interpretationown data§ Discussion
The PEST sequence does not appear to have a role in the enhancement of macrophage proliferation by PU.1.
“The PEST sequence does not appear to have a role in the enhancement of macrophage proliferation by PU.1.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Discussion
The fact that enhancement of macrophage proliferation is M-CSF or GM-CSF dependent probably rules out the possibility that PU.1 and PU.1-associated factors stabilize TFIID to allow assembly of the initiation complex of genes related to proliferation.
“However, the fact that en- hancement of macrophage proliferation is M-CSF or GM- CSF dependent probably rules out this possibility.”
Quote in the paperSubstantial claim - Interpretationown data§ Results
It is likely, at least in macrophages, that phosphorylation of amino acids 41 and/or 45 results in the activation of a domain important for the activity of PU.1.
“It is therefore likely, at least in macrophages, that phosphorylation of amino ac- ids 41 and/or 45 results in the activation of a domain im- portant for the activity of PU. 1.”
Quote in the paperSubstantial claim- Rests on an assumption: Alanine substitution at serine 41 or 45 does not alter PU.1 function except by preventing phosphorylation.
- Premisecitation§ Discussion
PU.1 binds to a specific site in the M-CSF receptor promoter just upstream from the major transcription initiation site.
“PU.1 binds to a specific site in the M-CSF receptor promoter just upstream from the major transcription initiation site.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17]
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- Premisecitation§ Discussion
PU.1 transactivates a reporter construct containing the M-CSF promoter.
“PU. 1 transactivates a reporter construct containing the M-CSF promoter. These experiments were performed by cotransfection in cells that normally do not express PU. 1 or the M-CSF receptor, with PU.1 cDNA and a reporter construct containing the M-CSF promoter (17).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17]
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- Interpretationreasoning§ Discussion
Flanking sequence influence may be part of the explanation for why PU.1 has an effect on macrophage proliferation, but not ets-2 or fli-1.
“This may be part of the ex- planation for why PU.1 has an effect on macrophage pro- liferation, but not ets-2 or fli-1.”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Discussion
The enhancement of macrophage proliferation induced by transfection of PU.1 appears to be related to the presence of M-CSF in the media.
“The enhancement of macrophage proliferation induced by the transfection of PU.1 appears to be related to the presence of M-CSF in the media.”
Quote in the paperSubstantial claim- Rests on an assumption: The M-CSF-dependent proliferation of BMDM reflects normal macrophage proliferation.
- May combine two claims. 11
- Classified as probably not a substantial claim. 24
May combine two claims.
Findingown data§ ResultsPU.1 protein carrying an alanine substitution at S41 or S45 fails to stimulate proliferation and lowers the basal level of proliferation.
“In contrast, PU.1 protein carrying an alanine substitution at $41 or $45 not only failed to stimulate pro- liferation, but also lowered the basal level of proliferation.”
Quote in the paperSubstantial claim- Rests on an assumption: Alanine substitution at serine 41 or 45 does not alter PU.1 function except by preventing phosphorylation.
- Rests on an assumption: The PU.1 constructs are expressed and function as intended in BMDM.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ ResultsPU.1 in routine macrophages is phosphorylated on five serines that are consensus sites for casein kinase II (CK II).
“The PU.1 transcription factor in routine macrophages is known to be phosphorylated on five serines that are con- sensus sites for casein kinase II (CK II) (9, and our unpub- lished results).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [9]
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Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ ResultsThe PEST domain of PU.1 is important for protein-protein interactions in B cells.
“The PEST domain has been shown to be important for the interaction ofPU. 1 with the B cell-specific factor NF-EM5 (Pip) (8, 24).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [8]
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- cites [24]
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Study design and conductown data§ Materials and MethodsA computer-assisted search of GenBank revealed little homology between the PU.1 antisense oligodeoxynucleotides and other mammalian genes.
“A computer-assisted search of the GenBank database for mammalian sequences complementary to these anti- sense oligodeoxynucleotides revealed little homology with other genes.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationreasoning§ ResultsThe decrease in proliferation observed with the PU.1 DNA-binding domain may be due to competition between endogenous PU.1 and the transfected DNA-binding domain for a target sequence in a promoter or enhancer of a gene or genes involved in proliferation.
“The decrease in proliferation observed when the DNA-binding domain was used may be due to the competiton between the endogenous PU.1 and the transfected DNA-binding domain for a target sequence in a promoter or enhancer of a gene or genes involved in pro- liferation.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone given§ Materials and MethodsEach experiment was performed at least five times and results expressed as mean ± SD; statistical analyses used Student's paired t test comparing at least five independent experiments.
“Each experiment was performed at least five times and the results are expressed as the mean + SD. Statistical analyses were performed using the Student's paired t test, comparing the results of at least five independent experiments.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ ResultsPU.1 has been shown to bind to the promoter of the M-CSF receptor and may be important for regulated expression of this receptor.
“PU. 1 has been shown to bind to the promoter of the M-CSF re- ceptor and therefore may be an important factor for the regulated expression of this receptor (17, 42).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [17]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [42]
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§ SummaryPU.1 is a tissue-specific transcription factor expressed in cells of the hematopoietic lineage, including macrophages, granulocytes, and B lymphocytes.
“PU.1 is a tissue-specific transcription factor that is expressed in cells of the hematopoietic lineage including macrophages, granulocytes, and B lymphocytes.”
- Also stated in: § Introduction · plain
“This protein is expressed in macrophages, granulocytes, mast cells, osteoclasts, and B lymphocytes (5).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [4]
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- cites [5]
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- Also stated in: § Introduction · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone given§ Materials and MethodsThe growth activity of LCM could be blocked by a specific mAb against M-CSF.
“The growth activity of LCM could be blocked by a specific mAb against M-CSF.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown data§ Materials and MethodsThe amount of DNA used was 2 mg for 12 * 10^6 cells, resulting in 7-12% transfection efficiency.
“The amount of DNA used was 2 mg for 12 * 106 cells, which resulted in 7-12% of cells being transfected, as assessed by staining for green fluorescent protein.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ DiscussionPU.1 is needed for expression from the J chain gene promoter.
“A dominant negative expression construct of PU.1 in which aminos acids 133 to the end were expressed was used to show that PU. 1 was needed for expression from the J chain gene promoter (12).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12]
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Probably not a substantial claim: may not pass S3 (load-bearing).
Interpretationcitation§ DiscussionThe reversion of the Ras-transformed phenotype by a dominant negative PU.1 construct may be due to a general feature of the DNA-binding domains of ETS family members.
“This latter result may be due to a general feature of the DNA-binding domains of ETS family mem- bers since dominant negative constructs of ets-1 and ets-2 had the same effect.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ DiscussionIn vitro, PU.1 interacts with the general transcription factor TFIID.
“In vitro, PU.1 was also shown to interact with the general transcription factor TFIID (49).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [49]
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§ DiscussionPU.1 perturbs the pathway that controls the potential for proliferation in erythroblasts.
“The infec- tion of erythroblasts with a retroviral vector expressing PU.1 was efficient for immortalization, suggesting that PU.1 perturbs the pathway that controls the potential for proliferation in these cells (48).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [48]
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§ DiscussionA dominant negative PU.1 expression construct (amino acids 160-266) transfected into Ras-transformed NIH3T3 fibroblasts reverts the transformed phenotype.
“A dominant negative PU.1 expression construct (amino acids 160-266) transfected into Ras- transformed NIH3T3 fibroblasts reverted the transformed phenotype (52).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [52]
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). May combine two claims.
Premisecitation§ DiscussionPU.1 binds the tumor suppressor protein p53, which represses cell proliferation.
“For instance, PU.1 binds the tumor suppressor protein p53 which represses cell proliferation (49).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [49]
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), S4 (based).
Interpretationown data§ DiscussionThe lack of effect of ets-2 on M-CSF-dependent macrophage proliferation may be due to an already high level of ets-2 expression in the cells.
“This may be due to an already high level of ets-2 expression in the cells (our unpublished results).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Interpretationreasoning§ DiscussionThe M-CSF receptor (c-fms) is a possible candidate gene mediating PU.1 enhancement of macrophage proliferation because the enhancement requires M-CSF.
“Because the enhancement of proliferation requires the presence of the growth factor M-CSF, one pos- sible candidate is the M-CSF receptor (c-fms), which is spe- cifically expressed in macrophages (3).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3]
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). May combine two claims.
Premisecitation§ DiscussionThe Ets family consists of a large number of proteins that have sequence identity within the DNA-binding domain, and all bind to a sequence containing the core sequence 5'-GGAA/T-3'.
“The Ets family consists of a large number of proteins that have sequence identity within the DNA-binding domain, and all bind to a se- quence containing the core sequence 5'-GGAA/T-3' (43).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [43]
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§ Discussionets-2 transactivates the proximal promoter of the M-CSF receptor.
“It has also been reported that ets-2 transactivates the proximal pro- moter of the M-CSF receptor (42, 53).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [42]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [53]
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). May combine two claims.
Premisecitation§ DiscussionThe protein-protein interaction between PU.1 and NF-EM5 is mediated through a 43-amino acid region with sequence homology to a PEST domain, which is susceptible to protease degradation.
“The protein-protein interaction is mediated through a 43--amino acid region with sequence homology to a PEST domain, i.e., one that is rich in proline (P), glutamic acid (E), serine (S), and threonine (T), which is susceptible to protease degradation (51).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [51]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Premisecitation§ DiscussionIn the SFFV model, if the provirus integrates upstream of the PU.1 gene, PU.1 is overexpressed and the cell loses its commitment to terminally differentiate and becomes immortal.
“In this model, if the provirus integrates up- stream of the PU.I gene, PU.1 is overexpressed and the cell loses its commitment to terminally differentiate and be- comes immortal.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [46]
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§ DiscussionPU.1 functions in association with other factors.
“PU.1 functions in association with other factors (8, 10, 19, 49, 50).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [8]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [10]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [19]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Premisecitation§ DiscussionMutations at the PU.1 binding site in the M-CSF receptor promoter eliminate PU.1 binding and decrease promoter activity.
“Mutations at this site have been shown to eliminate PU.1 binding and decrease promoter activity.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17]
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§ DiscussionAntisense oligodeoxynucleotides of PU.1 inhibit the proliferation of erythroleukemia cells induced by the retrovirus SFFV.
“Antisense ohgodeoxynucleotides of PU. 1 inhibit the prolif- eration of erythroleukemia cells induced by the retrovirus SFFV (46).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [46]
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§ DiscussionIn the mouse, at the K 3' enhancer, PU.1 recruits a B cell-restricted factor, NF-EM5 (Pip).
“In the mouse, K 3' enhancer for example, PU.1 recruits a B cell-restricted factor, NF-EM5 (Pip) (8, 24).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [8]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [24]
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). May combine two claims.
Interpretationcitation§ DiscussionPU.1 and PU.1-associated factor(s) could stabilize TFIID and allow assembly of the initiation complex of genes related to proliferation.
“PU.1 and PU.l-associated factor(s) could sta- bilize TFIID and allow assembly of the initiation complex of genes related to proliferation.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ DiscussionFlanking sequences influence the binding of specific Ets family members to DNA.
“Whereas the core sequence appears to be necessary for binding it is known that flanking sequences also influence the binding of specific Ets family members to DNA (44, and our unpublished results).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
The paper relies on this without support.
In vivo, PU.1 is phosphorylated on several serine residues.
“In vivo, PU. 1 is phosphorylated on several serine residues.”
The paper relies on this without support.
The macrophage cell lines IC-21, RAW264.7, and 2F5A express PU.1 endogenously.
“The prolifera- tion of three macrophage cell lines, IC-21, RAW264.7, and 2F5A, which express PU.1 endogenously, were tested using the sense and antisense constructs, and no effect on proliferation was observed (data not shown).”
The paper relies on this without support.
The cell line used to test M-CSF independence is truly M-CSF-independent.
“Interestingly, there was no effect of sense or antisense constructs of PU.1 on the proliferation of the M-CSF-independent cell line, suggesting that the response was M-CSF dependent.”
The paper relies on this without support.
The antisense and transfection experiments specifically modulate PU.1 activity without off-target effects.
“The block in macrophage prolif- eration using either an antisense PU. 1 expression construct or antisense oligonucleotides suggests that PU.1 plays a critical role in the proliferation of macrophages.”
The paper relies on this without support.
BMDM proliferation is a valid measure of macrophage proliferation.
“When a PU. 1 expression construct lacking the PEST do- main was transfected into BMDM, an enhancement of macrophage proliferation similar to that obtained using the wild PU. 1 construction was observed”
The paper relies on this without support.
Alanine substitution at serine 41 or 45 does not alter PU.1 function except by preventing phosphorylation.
“In contrast, PU.1 protein carrying an alanine substitution at $41 or $45 not only failed to stimulate pro- liferation, but also lowered the basal level of proliferation.”
The paper relies on this without support.
The PU.1 constructs are expressed and function as intended in BMDM.
“PU.1 with the $132/133A or $148A mutations was as active as the wild-type protein in stimulating proliferation of BMDM (Fig. 7 B).”
The paper relies on this without support.
The M-CSF-dependent proliferation of BMDM reflects normal macrophage proliferation.
“The enhancement of macrophage proliferation induced by the transfection of PU.1 appears to be related to the presence of M-CSF in the media.”
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?
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).”
From c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor (1999) · cites this paper as [54]
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 measuredPhosphorylation of two serine residues (positions 41 and 45) located at one of the acidic transactivation domains is necessary for macrophage colony-stimulating factor-dependent proliferation of bone marrow macrophages.
“phosphorylation of two serine residues (positions 41 and 45) located at one of the acidic transactivation domains is necessary for macrophage colony-stimulating factor-dependent proliferation of bone marrow macrophages (4)”
From Interleukin-3 Stimulation of <i>mcl-1</i> Gene Transcription Involves Activation of the PU.1 Transcription Factor through a p38 Mitogen-Activated Protein Kinase-Dependent Pathway (2003) · cites this paper as [4]
The Results (Fig. 7B; page not supplied) report that substituting alanine for serine 41 or 45 prevented PU.1 from enhancing proliferation of bone marrow-derived macrophages and lowered basal proliferation. The paper infers that phosphorylation at one or both positions likely activates an important domain, but does not establish that phosphorylation of both is necessary or identify that domain as acidic. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe 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).”
From c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor (1999) · cites this paper as [54]
PU.1 is known to be a vital transcription factor to regulate macrophage proliferation and differentiation as well as microgliogenesis in the developing brain.
“PU.1 is known to be a vital transcription factor to regulate macrophage proliferation (54) and differentiation (55) as well as microgliogenesis (13) in the developing brain.”
From Arresting the bad seed: HDAC3 regulates proliferation of different microglia after ischemic stroke (2024) · cites this paper as [54]
PU.1 controls proliferation of macrophages by upregulating the receptor for M-CSF.
“Moreover, PU.1 controls proliferation of macrophages by upregulating the receptor for M-CSF34.”
From MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α–PU.1 pathway (2011) · cites this paper as [34]
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.
DNA-binding-domain result points to the wrong figure panel
MinorThe text cites Fig. 7 B for the DNA-binding-domain experiment, but the figure caption assigns that experiment to panel A; panel B concerns serine mutations.
“A decrease in M-CSF-dependent proliferation, however, was observed when a PU.1 construct containing the DNA- binding domain (ETS domain) was transfected into the cells (Fig. 7 B).”
“Figure 7. (A) The DNA-binding domainofPU.1 inhibitsM-CSF--dependentproliferation.”
Cites
Green fluorescent protein as a marker for gene expression
Chalfie, M., Tu, Y., Euskirchen, G., Ward, W. W., & Prasher, D. C. (1994) · Science · doi:10.1126/science.8303295 · Cited by 6,802 · cited 1× · see citing works
“After 2 d of culture, cells were fixed, stained, and counted (29).”
BackgroundAmino Acid Sequences Common to Rapidly Degraded Proteins: The PEST Hypothesis
Rogers, S. W., Wells, R., & RECHSTEINER, M. C. (1986) · Science · doi:10.1126/science.2876518 · Cited by 2,565 · cited 1× · see citing works
“, one that is rich in proline (P), glutamic acid (E), serine (S), and threonine (T), which is susceptible to protease degradation (51).”
BackgroundLuckow, B., & Schütz, G. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.13.5490 · Cited by 1,650 · see citing works
Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages
Scott, E. W., Simon, M. C., Anastasi, J., & Singh, H. (1994) · Science · doi:10.1126/science.8079170 · Cited by 1,532 · cited 1× · see citing works
“(25) have reported the absence o f h o m o zygous mutant progeny, suggesting that disruption o f PU.”
BackgroundEllis, L., Clauser, E., Morgan, D. O., Edery, M., Roth, R. A., & Rutter, W. J. (1986) · Cell · doi:10.1016/0092-8674(86)90786-5 · Cited by 1,070 · see citing works
Metcalf, D. (1989) · Nature · doi:10.1038/339027a0 · Cited by 1,023 · see citing works
The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene
Klemsz, M. J., McKercher, S. R., Celada, A., Van Beveren, C., & Maki, R. A. (1990) · Cell · doi:10.1016/0092-8674(90)90219-5 · Cited by 954 · see citing works
Self-citationGene inhibition using antisense oligodeoxynucleotides
Wagner, R. W. (1994) · Nature · doi:10.1038/372333a0 · Cited by 747 · cited 1× · see citing works
“into the functional importance of a variety of genes (45).”
BackgroundGunning, P. W., Leavitt, J. C., Muscat, G. E. O., Ng, S. Y., & Kedes, L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.14.4831 · Cited by 739 · cited 1× · see citing works
“I cDNA into the HindlII - Sal sites of the pHb APr-l-neo vector in the reverse orientation (32).”
MethodPhysicochemical properties of phospborothioate oligodeoxynucleotides
Stein, C. A., Subasinghe, C., Shinozuka, K., & Cohen, J. S. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.8.3209 · Cited by 593 · see citing works
The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence.
Karim, F. D., Urness, L. D., Thummel, C. S., Klemsz, M. J., McKercher, S. R., Celada, A., Van Beveren, C., Maki, R. A., Gunther, C. V., & Nye, J. A. (1990) · Genes & Development · doi:10.1101/gad.4.9.1451 · Cited by 499 · cited 2× · see citing works
“1 belongs to a large family o f related D N A binding proteins (Ets family) (43, 44), we were interested in determining whether the effect of PU.”
BackgroundSelf-citationEvidence for a gamma-interferon receptor that regulates macrophage tumoricidal activity.
Celada, A., Gray, P. W., Rinderknecht, E., & Schreiber, R. D. (1984) · The Journal of Experimental Medicine · doi:10.1084/jem.160.1.55 · Cited by 465 · cited 1× · see citing works
“Macrophages derived from bone marrow cultures (BMDM) 1 were obtained as described (27).”
MethodSelf-citationSpi-1 is a putative oncogene in virally induced murine erythroleukaemias
Moreau-Gachelin, F., Tavitian, A., & Tambourin, P. (1988) · Nature · doi:10.1038/331277a0 · Cited by 447 · cited 3× · see citing works
“1 interacts with the B cell--specific factor N F - E M 5 (Pip) and stimulates transcription from the Ig K 3' enhancer (7, 24).”
BackgroundPip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent transcriptional activator.
Eisenbeis, C. F., Singh, H., & Storb, U. (1995) · Genes & Development · doi:10.1101/gad.9.11.1377 · Cited by 447 · cited 3× · see citing works
“with the B cell-specific factor NF-EM5 (Pip) (8, 24).”
BackgroundZhang, D. E., Hetherington, C. J., Chen, H. M., & Tenen, D. G. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.1.373 · Cited by 411 · see citing works
Zhang, D.-E., Hetherington, C. J., Chen, H.-M., & Tenen, D. G. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.1.373-381.1994 · Cited by 411 · cited 4× · see citing works
“1 directs the expression of the M-CSF receptor (17, 42, 53).”
BackgroundInfluentialWarren, M. K., & Ralph, P. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.137.7.2281 · Cited by 392 · see citing works
Pongubala, J. M., Nagulapalli, S., Klemsz, M. J., McKercher, S. R., Maki, R. A., & Atchison, M. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.1.368 · Cited by 354 · see citing works
Self-citationColony-stimulating factor-1 receptor
Sherr, C. (1990) · Blood · doi:10.1182/blood.v75.1.1.bloodjournal7511 · Cited by 353 · cited 2× · see citing works
“The receptor for the growth factor M-CSF, the product of the c-fins gene, has been well characterized (3).”
BackgroundMacleod, K., Leprince, D., & Stehelin, D. (1992) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(92)90404-w · Cited by 304 · see citing works
Hagemeier, C., Bannister, A. J., Cook, A., & Kouzarides, T. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.4.1580 · Cited by 303 · see citing works
The proto-oncogene PU.1 regulates expression of the myeloid-specific CD11b promoter
Pahl, H. L., Scheibe, R. J., Zhang, D. E., Chen, H. M., Galson, D. L., Maki, R. A., & Tenen, D. G. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53496-7 · Cited by 301 · see citing works
Self-citationDual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity
Graupner, G., Wills, K. N., Tzukerman, M., Zhang, X.-K., & Pfahl, M. (1989) · Nature · doi:10.1038/340653a0 · Cited by 294 · cited 2× · see citing works
“The retinoic acid receptor e/a3 pECE was a gift from M. Pfahl (La Jolla Cancer Research Foundation) (31).”
Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation
Pongubala, J., Van Beveren, C., Nagulapalli, S., Klemsz, M., McKercher, Maki, R., & Atchison, M. (1993) · Science · doi:10.1126/science.8456286 · Cited by 282 · cited 1× · see citing works
“1 in lymphocytes include the Ig K light chain gene 3' enhancer (8, 9), the Ig k 2-4 enhancer (10), the Ig heavy chain p, en-”
BackgroundSelf-citationRegulation of lymphoid-specific immunoglobulin mu heavy chain gene enhancer by ETS-domain proteins
Nelsen, B., Tian, G., Erman, B., Gregoire, J., Maki, R., Graves, B., & Sen, R. (1993) · Science · doi:10.1126/science.8316859 · Cited by 222 · see citing works
Self-citationChen, H. M., Pahl, H. L., Scheibe, R. J., Zhang, D. E., & Tenen, D. G. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53086-6 · Cited by 199 · see citing works
Olson, M. C., Scott, E. W., Hack, A. A., Su, G. H., Tenen, D. G., Singh, H., & Simon, M. C. (1995) · Immunity · doi:10.1016/1074-7613(95)90060-8 · Cited by 191 · see citing works
Grove, M., & Plumb, M. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.9.5276-5289.1993 · Cited by 190 · see citing works
Eisenbeis, C. F., Singh, H., & Storb, U. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.10.6452 · Cited by 182 · see citing works
Grove, M., & Plumb, M. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.9.5276 · Cited by 174 · see citing works
Horiguchi, J., Warren, M. K., & Kufe, D. W. (1987) · Blood · doi:10.1182/blood.v69.4.1259.1259 · Cited by 167 · cited 1× · see citing works
“GM-CSF is known to induce the expression of M-CSF (38-41).”
BackgroundGalson, D. L., Hensold, J. O., Bishop, T. R., Schalling, M., D'Andrea, A. D., Jones, C., Auron, P. E., & Housman, D. E. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.5.2929 · Cited by 147 · see citing works
Kominato, Y., Galson, D. L., Waterman, W. R., Webb, A. C., & Auron, P. E. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.1.59 · Cited by 146 · see citing works
Hagman, J., & Grosschedl, R. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.19.8889 · Cited by 143 · see citing works
Shin, M. K., & Koshland, M. E. (1993) · Genes & Development · doi:10.1101/gad.7.10.2006 · Cited by 126 · see citing works
Reddy, M. A., Yang, B. S., Yue, X., Barnett, C. J., Ross, I. L., Sweet, M. J., Hume, D. A., & Ostrowski, M. C. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.180.6.2309 · Cited by 123 · see citing works
The PU.1 transcription factor is the product of the putative oncogene Spi-1
Goebl, M. G. (1990) · Cell · doi:10.1016/0092-8674(90)90676-6 · Cited by 120 · see citing works
Eichbaum, Q. G., Iyer, R., Raveh, D., Mathieu, C., & Ezekowitz, R. A. B. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.6.1985 · Cited by 119 · see citing works
Spi-1/PU.1: an oncogene of the Ets family
Moreau-Gachelin, F. (1994) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/0304-419x(94)90011-6 · Cited by 110 · cited 1× · see citing works
“This protein is expressed in macrophages, granulocytes, mast cells, osteoclasts, and B lymphocytes (5).”
BackgroundPU.1 Recruits a Second Nuclear Factor to a Site Important for Immunoglobulin κ 3' Enhancer Activity
Pongubala, J. M. R., Nagulapalli, S., Klemsz, M. J., McKercher, S. R., Maki, R. A., & Atchison, M. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.1.368-378.1992 · Cited by 105 · see citing works
Self-citationCD18 (beta 2 leukocyte integrin) promoter requires PU.1 transcription factor for myeloid activity.
Rosmarin, A. G., Caprio, D. G., Levy, R., & Simkevich, C. P. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.3.801 · Cited by 94 · cited 1× · see citing works
“1 is believed to regulate the expression in macrophages o f several receptors, which include the Fc ' , /RI~ gene (15), the Fc~/PdlIA gene (16), the M - C S F receptor gene (17), the CD11b gene (18, 19), the scavenger receptor (20), the macrophage inflammatory protein lc~ (MIP- lo 0 (21), IL-113 (22), and CD18 (23).”
BackgroundFeinman, R., Qiu, W. Q., Pearse, R. N., Nikolajczyk, B. S., Sen, R., Sheffery, M., & Ravetch, J. V. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06696.x · Cited by 88 · see citing works
The Ets-Related Transcription Factor PU.1 Immortalizes Erythroblasts
Schuetze, S. M., Stenberg, P. E., & Kabat, D. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.9.5670 · Cited by 87 · see citing works
Moulton, K. S., Semple, K., Wu, H., & Glass, C. K. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.7.4408 · Cited by 86 · see citing works
Role of the PU.1 Transcription Factor in Controlling Differentiation of Friend Erythroleukemia Cells
Schuetze, S. M., Paul, R. W., Gliniak, B., & Kabat, D. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.7.2967 · Cited by 85 · see citing works
Characterization of the ets oncogene family member, fli-1.
Klemsz, M. J., Maki, R. A., Papayannopoulou, T., Moore, J., & Hromas, R. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53385-8 · Cited by 84 · see citing works
Self-citationCelada, A., & Maki, R. A. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.148.4.1102 · Cited by 80 · see citing works
Self-citationCelada, A., & Maki, R. A. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.1.114 · Cited by 67 · see citing works
Self-citation(1994) · PubMed · Cited by 67 · see citing works
BLyF, a Novel Cell-Type- and Stage-Specific Regulator of the B-Lymphocyte Gene mb-1
Feldhaus, A. L., Mbangkollo, D., Arvin, K. L., Klug, C. A., & Singh, H. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.3.1126-1133.1992 · Cited by 66 · cited 1× · see citing works
“hancer (11), the I g J chain gene (12), and the rob-1 gene, which is expressed in early B cell differentiation (13, 14).”
BackgroundRoss, I. L., Dunn, T. L., Yue, X., Himes, S. R., Barnett, C. J. K., & Hume, D. A. (1994) · PubMed · Cited by 57 · see citing works
Galson, D. L., Hensold, J. O., Bishop, T. R., Schalling, M., D'Andrea, A. D., Jones, C., Auron, P. E., & Housman, D. E. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.5.2929-2941.1993 · Cited by 45 · see citing works
Inhibition of Friend cells proliferation by spi-1 antisense oligodeoxynucleotides.
Delgado, M. D., Hallier, M., Meneceur, P., Tavitian, A., & Moreau-Gachelin, F. (1994) · PubMed · Cited by 44 · see citing works
The Ets-Related Transcription Factor PU.1 Immortalizes Erythroblasts
Schuetze, S. M., Stenberg, P. E., & Kabat, D. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.9.5670-5678.1993 · Cited by 42 · cited 1× · see citing works
“1 perturbs the pathway that controls the potential for proliferation in these cells (48).”
BackgroundEisenbeis, C. F., Singh, H., & Storb, U. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.10.6452-6461.1993 · Cited by 38 · cited 2× · see citing works
“1 in lymphocytes include the Ig K light chain gene 3' enhancer (8, 9), the Ig k 2-4 enhancer (10), the Ig heavy chain p, en-”
BackgroundLokeshwar, B. L., & Lin, H. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.141.2.483 · Cited by 32 · see citing works
Role of the PU.1 Transcription Factor in Controlling Differentiation of Friend Erythroleukemia Cells
Schuetze, S. M., Paul, R. W., Gliniak, B., et al. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.7.2967-2975.1992 · Cited by 31 · cited 1× · see citing works
“differentiation and the loss of immortality (47).”
Birchenall-Roberts, M. C., Ferrer, C., Ferris, D. K., Falk, L. A., Kasper, J. J., White, G., & Ruscetti, F. W. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.145.10.3290 · Cited by 23 · see citing works
The regulatory effects of macrophages on colony stimulating factor-1 (CSF-1) production
Wu, J., Jiang-Qin, Z., Zhu, D., et al. (1990) · International Journal of Biochemistry · doi:10.1016/0020-711x(90)90266-6 · Cited by 4 · see citing works
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Pulmonary Alveolar Proteinosis
Trapnell, B. C., Whitsett, J. A., & Nakata, K. (2003) · New England Journal of Medicine · doi:10.1056/nejmra023226 · Cited by 790 · see citing works
Ponomarev, E. D., Veremeyko, T., Barteneva, N., Krichevsky, A. M., & Weiner, H. L. (2011) · Nature Medicine · doi:10.1038/nm.2266 · Cited by 787 · see citing works
“1 controls proliferation of macrophages by upregulating the receptor for M-CS”
Pulmonary Alveolar Proteinosis: Progress in the First 44 Years
Seymour, J. F., & Presneill, J. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2109105 · Cited by 697 · see citing works
Transcription Factors, Normal Myeloid Development, and Leukemia
Tenen, D. G., Hromas, R., Licht, J. D., & Zhang, D.-E. (1997) · Blood · doi:10.1182/blood.v90.2.489 · Cited by 735 · see citing works
GM-CSF Regulates Alveolar Macrophage Differentiation and Innate Immunity in the Lung through PU.1
Shibata, Y., Berclaz, P., Chroneos, Z. C., Yoshida, M., Whitsett, J. A., & Trapnell, B. C. (2001) · Immunity · doi:10.1016/s1074-7613(01)00218-7 · Cited by 613 · see citing works
“AMs are vital to normal lung PU.1 promotes both the proliferation (Celada et al., 1996)surfactant metabolism, to which they contribute by caand differentiation (DeKoter et al., 1998) of myeloid pro-tabolism of both surfactant lipids and surfactant progenitors.”
BackgroundThe AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis
Fidler, T. P., Xue, C., Yalçınkaya, M., Hardaway, B., Abramowicz, S., Xiao, T., Liu, W., Thomas, D. G., Hajebrahimi, M. A., Pircher, J., et al. (2021) · Nature · doi:10.1038/s41586-021-03341-5 · Cited by 471 · see citing works
Regulation of Microglial Proliferation during Chronic Neurodegeneration
Gómez-Nicola, D., Fransen, N. L., Suzzi, S., & Perry, V. H. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4440-12.2013 · Cited by 407 · see citing works
“PU.1 is a master regulator of myeloid differentiation and induces the expression of CD45, CD11b, F4/ 80, and MHC class II as well as regulating cell proliferation by upregulating the CSF1R (Celada et al., 1996; Nishiyama et al., 2004).”
BackgroundTrapnell, B. C., & Whitsett, J. A. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.090601.113847 · Cited by 353 · see citing works
Diseases of Pulmonary Surfactant Homeostasis
Whitsett, J. A., Wert, S. E., & Weaver, T. E. (2015) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104644 · Cited by 251 · see citing works
Transcription factors that regulate monocyte/macrophage differentiation
Valledor, A. F., Borràs, F. E., Cullell-Young, M., & Celada, A. (1998) · Journal of Leukocyte Biology · doi:10.1002/jlb.63.4.405 · Cited by 211 · see citing works
“1 increased the M-CSF-dependent proliferation of these cells [12].”
BackgroundSelf-citationRegulation of interleukin-12 production in antigen-presenting cells
Mal, X., & Trinchieri, G. (2001) · Advances in immunology · doi:10.1016/s0065-2776(01)79002-5 · Cited by 213 · see citing works
OxInflammation: From Subclinical Condition to Pathological Biomarker
Valacchi, G., Virgili, F., Cervellati, C., & Pecorelli, A. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00858 · Cited by 206 · see citing works
“It is well known that these factors are master regulators of genes associated with differentiation, proliferation, and migration of immune cells and resident vascular cells, and modulate the expression of a plethora of proinflammatory and immune factors (Celada et al., 1996).”
BackgroundLiu, J., Cao, S., Kim, S. J., Chung, E. Y., Homma, Y., Guan, X., Jimenez, V., & Ma, X. (2005) · Current Immunology Reviews · doi:10.2174/1573395054065115 · Cited by 189 · see citing works
“It is expressed predominantly in macrophages, B-cells, and erythroid cells [179,180].”
BackgroundNutma, E., Fancy, N. N., Weinert, M., Tsartsalis, S., Marzin, M. C., Muirhead, R. C. J., Falk, I. N., Breur, M., de Bruin, J., Hollaus, D., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40937-z · Cited by 192 · see citing works
“The PU.1 transcription factor is a master regulator of macrophage proliferation and macrophage differentiation 32,33 .”
c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor
Behre, G., Whitmarsh, A. J., Coghlan, M. P., Hoang, T., Carpenter, C. L., Zhang, D.-E., Davis, R. J., & Tenen, D. G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.8.4939 · Cited by 183 · see citing works
ETS transcription factors and regulation of immunity
Gallant, S., & Gilkeson, G. S. (2006) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-006-0017-z · Cited by 163 · see citing works
“1 levels directly impacts M-CSF-dependent proliferation of macrophages and myeloid progenitors [25, 33, 140, 197].”
BackgroundFisher, R. C., & Scott, E. W. (1998) · STEM CELLS · doi:10.1002/stem.160025 · Cited by 158 · 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
Autophagy Driven by a Master Regulator of Hematopoiesis
Kang, Y.-A., Sanalkumar, R., O'Geen, H., Linnemann, A. K., Chang, C.-J., Bouhassira, E. E., Farnham, P. J., Keles, S., & Bresnick, E. H. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06166-11 · Cited by 153 · see citing works
“Genome-wide studies of GATA-1 chromatin occupancy have analyzed endogenous GATA-1 in K562 erythroleukemia cells (9) and biotinylated GATA-1 in MEL cells (5, 56).”
BackgroundThe key role of PU.1/SPI-1 in B cells, myeloid cells and macrophages
Lloberas, J., Soler, C., & Celada, A. (1999) · Immunology Today · doi:10.1016/s0167-5699(99)01442-5 · Cited by 142 · see citing works
Self-citationYasueda, A., Mizushima, T., Nezu, R., Sumi, R., Tanaka, M., Nishimura, J., Kai, Y., Hirota, M., Osawa, H., Nakajima, K., et al. (2015) · Surgery Today · doi:10.1007/s00595-015-1261-9 · Cited by 141 · see citing works
“1 [42, 43], which is a tissuespecific transcription factor, resulting in the downregulation of the Toll-like receptor 4 (TLR4) expression [44].”
BackgroundValledor, A. F., Comalada, M., Xaus, J., & Celada, A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.10.7403 · Cited by 135 · see citing works
Self-citationRegulation 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
Molecular Mechanisms Involved in Macrophage Survival, Proliferation, Activation or Apoptosis
Xaus, J., Comalada, M., Valledor, A. F., Cardó, M., Herrero, C., Soler, C., Lloberas, J., & Celada, A. (2001) · Immunobiology · doi:10.1078/0171-2985-00091 · Cited by 130 · see citing works
Self-citationXaus, J., Comalada, M., Cardó, M., Valledor, A. F., & Celada, A. (2001) · Blood · doi:10.1182/blood.v98.7.2124 · Cited by 129 · see citing works
Self-citationMicroglia: unique and common features with other tissue macrophages
Prinz, M., Tay, T. L., Wolf, Y., & Jung, S. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1267-1 · Cited by 126 · see citing works
Liu, D., Chang, C., Lü, N., Wang, X., Lu, Q., Ren, X., Ren, P., Zhao, D., Wang, L., Zhu, Y., et al. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6b00604 · Cited by 120 · see citing works
Du, J., Stankiewicz, M. J., Liu, Y., Xi, Q., Schmitz, J. E., Lekstrom-Himes, J. A., & Ackerman, S. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204777200 · Cited by 120 · see citing works
The JNK Are Important for Development and Survival of Macrophages
Himes, S. R., Sester, D. P., Ravasi, T., Cronau, S. L., Sasmono, T., & Hume, D. A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.4.2219 · Cited by 117 · see citing works
“1 transcription factor has been shown to effect proliferation of BMMs in a CSF-1-dependent manner, and decreased proliferation of BMMs in response to JNK inhibition may partially occur through repression of c-fms gene expression (54) (Fig.”
BackgroundLau, S.-F., Chen, C., Fu, W.-Y., Qu, J. Y., Cheung, T. H., Fu, A. K. Y., & Ip, N. Y. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107530 · Cited by 114 · see citing works
Manea, S., Constantin, A. L., Manda, G., Sasson, S., & Manea, A. (2015) · Redox Biology · doi:10.1016/j.redox.2015.06.012 · Cited by 116 · see citing works
Oikawa, T., Yamada, T., Kihara-Negishi, F., Yamamoto, H., Kondoh, N., Hitomi, Y., & Hashimoto, Y. (1999) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4400534 · Cited by 109 · see citing works
Comalada, M., Xaus, J., Valledor, A. F., López, C., Pennington, D. J., & Celada, A. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00228.2003 · Cited by 109 · see citing works
“Because these cells cannot be transfected efficiently, we used specific chemical inhibitors (12).”
MethodSelf-citationSmith, A. M., Gibbons, H. M., Oldfield, R. L., Bergin, P. M., Mee, E. W., Curtis, M. A., Faull, R. L. M., & Dragunow, M. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-85 · Cited by 107 · see citing works
“1 has been shown to be involved in M-CSF -dependent proliferation of mouse bone-marrow macrophages [24] and thus it is likely that PU.”
BackgroundInfluentialOverexpression of sphingosine kinase 1 is an oncogenic event in erythroleukemic progression
Scolan, E. L., Pchejetski, D., Banno, Y., Denis, N., Mayeux, P., Vainchenker, W., Levade, T., & Moreau-Gachelin, F. (2005) · Blood · doi:10.1182/blood-2004-12-4832 · Cited by 107 · see citing works
Development and function of tissue resident macrophages in mice
Kierdorf, K., Prinz, M., Geissmann, F., & Perdiguero, E. G. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2016.03.017 · Cited by 106 · see citing works
Selective Roles of MAPKs during the Macrophage Response to IFN-γ
Valledor, A. F., Sànchez‐Tilló, E., Arpa, L., Park, J. M., Caelles, C., Lloberas, J., & Celada, A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.7.4523 · Cited by 97 · see citing works
“For our studies, we used homogeneous populations of primary bone marrow-derived macrophages, which become activated under the effect of IFN- (11, 20).”
MethodSelf-citationSuppression of IL-12 Transcription in Macrophages Following Fcγ Receptor Ligation
Cappiello, M. G., Sutterwala, F. S., Trinchieri, G., Mosser, D. M., & Ma, X. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.7.4498 · Cited by 98 · see citing works
“It is expressed predominantly in macrophages, B cells, and erythroid cells (27, 28).”
BackgroundShort telomeres protect from diet‐induced atherosclerosis in apolipoprotein E‐null mice
Poch, E., Carbonell, P., Franco, S., Díez‐Juan, A., Blasco, M. A., & Andrés, V. (2003) · The FASEB Journal · doi:10.1096/fj.03-0710fje · Cited by 94 · see citing works
“Splenocytes and bone marrow-derived macrophages were obtained from the pooled tissue from three mice as described previously (28, 33).”
MethodYeramian, A., Jaular, L. M., Arpa, L., Bertran, J., Soler, C., McLeod, C., Modolell, M., Palacı́n, M., Lloberas, J., & Celada, A. (2006) · European Journal of Immunology · doi:10.1002/eji.200535694 · Cited by 91 · see citing works
Self-citationSebastián, C., Herrero, C., Serra, M., Lloberas, J., Blasco, M. A., & Celada, A. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901131 · Cited by 90 · see citing works
“Macrophage proliferation was measured by [(3)H]thymidine incorporation as described (11).”
MethodSelf-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
“While phosphorylation of two serine residues (positions 41 and 45) located at one of the acidic transactivation domains is necessary for macrophage colony-stimulating factor-dependent proliferation of bone marrow macrophages (4), a serine phosphorylation at position 148 in the proline-, glutamic-acid-, serine-, and th…”
BackgroundXaus, J., Valledor, A. F., Cardó, M., Marqués, L., Beleta, J., Palacios, J. M., & Celada, A. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.8.4140 · Cited by 83 · see citing works
“In this report, we have used primary cultures of BMDM, which is an homogeneous population that responds to physiological proliferative or activating stimuli (54).”
MethodSelf-citationPU.1 but not ets-2 is essential for macrophage development from embryonic stem cells
Henkel, G., McKercher, Sr., Yamamoto, H., Anderson, K., Oshima, R., & Maki, R. (1996) · Blood · doi:10.1182/blood.v88.8.2917.bloodjournal8882917 · Cited by 76 · see citing works
Self-citationPU.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
“In some instances, binding of both factors to DNA is required; in others, PU.1 may actually tether another factor to the DNA, as has been reported for c-Jun on the M-CSF promoter and C/EBPβ on the IL-1β promoter (35,36).”
BackgroundInfluentialValledor, A. F., Xaus, J., Marqués, L., & Celada, A. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.5.2452 · Cited by 74 · see citing works
Self-citationWalton, M. R., Gibbons, H., MacGibbon, G. A., Sirimanne, E., Saura, J., Gluckman, P. D., & Dragunow, M. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00262-3 · Cited by 73 · see citing works
Decorin Reverses the Repressive Effect of Autocrine-Produced TGF-β on Mouse Macrophage Activation
Comalada, M., Cardó, M., Xaus, J., Valledor, A. F., Lloberas, J., Ventura, F., & Celada, A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.9.4450 · Cited by 68 · see citing works
“Bone marrow-derived macrophages were isolated from 6-wk-old BALB/c mice (Charles River Laboratories, Wilmington, MA) as previously described (16).”
MethodSelf-citationReview: 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
“(63,64) Importantly, serine 148 phosphorylation is required to enhance protein-protein interaction with IRF-4 or with ICSBP/IRF-8.”
MicroRNAs in the Brain: It's Regulatory Role in Neuroinflammation
Thounaojam, M. C., Kaushik, D. K., & Basu, A. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8400-3 · Cited by 66 · see citing works
“1 is a master regulator of macrophage cell differentiation and proliferation that play a crucial role in the activation of the phenotype of monocytic lineage [42].”
BSAP 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
“1 is known to influence macrophage proliferation (5), BSAP expression in early B-cell precursors could limit the expansion of cells into the myeloid pathway by inhibiting PU.”
BackgroundBellón, T., Perrotti, D., & Calabretta, B. (1997) · Blood · doi:10.1182/blood.v90.5.1828 · Cited by 62 · see citing works
Sànchez‐Tilló, E., Comalada, M., Xaus, J., Farrera, C., Valledor, A. F., Caelles, C., Lloberas, J., & Celada, A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609662200 · Cited by 61 · see citing works
Self-citationSierra, S., Lara‐Villoslada, F., Comalada, M., Olivares, M. M., & Xaus, J. (2006) · Lipids · doi:10.1007/s11745-006-5061-2 · Cited by 60 · see citing works
Luo, Q., Ma, X., Wahl, S. M., Bieker, J. J., Crossley, M., & Montaner, L. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400320200 · Cited by 59 · see citing works
Arresting the bad seed: HDAC3 regulates proliferation of different microglia after ischemic stroke
Zhang, Y., Li, J., Zhao, Y., Huang, Y., Shi, Z., Wang, H., Cao, H., Wang, C., Wang, Y., Chen, D., et al. (2024) · Science Advances · doi:10.1126/sciadv.ade6900 · Cited by 57 · see citing works
“PU.1 is known to be a vital transcription factor to regulate macrophage proliferation ( 54 ) and differentiation ( 55 ) as well as microglio-genesis ( 13 ) in the developing brain.”
BackgroundComalada, M., Xaus, J., Sànchez‐Tilló, E., Valledor, A. F., & Celada, A. (2004) · European Journal of Immunology · doi:10.1002/eji.200425110 · Cited by 57 · see citing works
Self-citationLiu, J., & Ma, X. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602059200 · Cited by 56 · see citing works
Evidence of recent signatures of selection during domestication in an Atlantic salmon population
Gutiérrez, A. P., Yañez, J. M., & Davidson, W. S. (2015) · Marine Genomics · doi:10.1016/j.margen.2015.12.007 · Cited by 56 · see citing works
“1, a transcription factor linked to macrophage proliferation (Celada et al., 1996), ESTV_12965_608 is associatedwith Sema6d a genewith a role in immune response and development (Vadasz and Toubi, 2014) and ESTV_16140_475 is associated with prothymosin α that has an immunoregulatory role during infection (Shiau et al.”
BackgroundSebastián, C., Serra, M., Yeramian, A., Serrat, N., Lloberas, J., & Celada, A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.9.5898 · Cited by 54 · see citing works
“Macrophage proliferation was measured by [(3)H]thymidine incorporation as described (26).”
MethodSelf-citationRieske, P., & Pongubala, J. R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007482200 · Cited by 53 · see citing works
Wontakal, S. N., Guo, X., Will, B., Shi, M., Raha, D., Mahajan, M. C., Weissman, S., Snyder, M., Steidl, U., Zheng, D., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001392 · Cited by 53 · see citing works
“1 has been reported to promote proliferation of both erythroid progenitors [10,43] and bone marrow derived macrophages [73].”
BackgroundGangenahalli, 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
“Bone marrow derived-macrophages transfected with an antisense PU.1 construct showed reduced proliferation as compared with controls, whereas those transfected with sense PU.1 construct displayed enhanced M-CSF-dependent proliferation (49).”
Quang, C. T., Wessely, O., Pironin, M., Beug, H., & Ghysdael, J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.18.5639 · Cited by 52 · see citing works
“…express high levels of Spi-1/PU.1 and require in the primary leukemic cells from which they were derived (Mowat et al., 1985; Chow et al., 1987; Ben-Davidthis transcription factor for their normal development (Scott et al., 1994; Celada et al., 1996; McKercher et al., 1990; Munroe et al., 1990).”
BackgroundCommitment to the Monocytic Lineage Occurs in the Absence of the Transcription Factor PU.1
Henkel, G. W., McKercher, S. R., Leenen, P. J. M., & Maki, R. A. (1999) · Blood · doi:10.1182/blood.v93.9.2849 · Cited by 53 · see citing works
Self-citationMicroRNAs as Novel Regulators of Neuroinflammation
Ksiazek-Winiarek, D. J., Kacperska, M. J., & Glabinski, A. R. (2013) · Mediators of Inflammation · doi:10.1155/2013/172351 · Cited by 50 · see citing works
“1 plays important role in the activation of monocytic lineage phenotype [117].”
BackgroundNBS1 is required for macrophage homeostasis and functional activity in mice
Pereira‐Lopes, S., Tur, J., Calatayud-Subias, J. A., Lloberas, J., Stracker, T. H., & Celada, A. (2015) · Blood · doi:10.1182/blood-2015-04-637371 · Cited by 50 · see citing works
“BM-derived macrophages (BMDMs) were generated as described.(21) A homogeneous populationof adherentmacrophageswasobtainedafter 7 daysof culture (.”
MethodInfluentialSelf-citationFisher, R. C., Olson, M. C., Pongubala, J. M. R., Perkel, J. M., Atchison, M. L., Scott, E. W., & Simon, M. C. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.4347 · Cited by 49 · see citing works
“1 activation domain have been implicated in the M-CSF-dependent proliferation of murine bone marrow macrophages (4).”
BackgroundMonocyte depletion increases local proliferation of macrophage subsets after skeletal muscle injury
Côt́e, C. H., Bouchard, P., van Rooijen, N., Marsolais, D., & Duchesne, É. (2013) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-14-359 · Cited by 48 · see citing works
“This is in accordance with the reported proliferative ability of a number of macrophage subtypes including macrophages located in brain [35,37] or peritoneum [38], bone marrow-derived macrophages in culture [39], and the macrophage cell line RAW-264.”
ResultThe ETS Family of Transcriptional Regulators
Ghysdael, J., & Boureux, A. (1997) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-8889-9_2 · Cited by 48 · see citing works
Valproic acid induces microglial dysfunction, not apoptosis, in human glial cultures
Gibbons, H. M., Smith, A. M., Teoh, H. H., Bergin, P. M., Mee, E. W., Faull, R. L. M., & Dragunow, M. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.08.024 · Cited by 49 · see citing works
Casals‐Casas, C., Álvarez, E., Serra, M., de la Torre, C., Farrera, C., Sànchez‐Tilló, E., Caelles, C., Lloberas, J., & Celada, A. (2009) · European Journal of Immunology · doi:10.1002/eji.200839037 · Cited by 48 · see citing works
Self-citationCasals, C., Barrachina, M., Serra, M., Lloberas, J., & Celada, A. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.10.6307 · Cited by 48 · see citing works
Self-citationValledor, A. F., Arpa, L., Sànchez‐Tilló, E., Comalada, M., Casals, C., Xaus, J., Caelles, C., Lloberas, J., & Celada, A. (2008) · Blood · doi:10.1182/blood-2007-11-123604 · Cited by 48 · see citing works
Self-citationRao, S., Matsumura, A., Yoon, J. W., & Simon, M. C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.16.11115 · Cited by 46 · see citing works
Kim, J., Kim, H., Kwon, S. B., Lee, S. Y., Chung, S., Jeong, D., & Min, B. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.09.220 · Cited by 47 · see citing works
Tsubakimoto, Y., Yamada, H., Yokoi, H., Kishida, S., Takata, H., Kawahito, H., Matsui, A., Urao, N., Nozawa, Y., Hirai, H., et al. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.187732 · Cited by 46 · see citing works
Jones, R. E., Andrews, R., Holmans, P., Hill, M., & Taylor, P. R. (2021) · Scientific Reports · doi:10.1038/s41598-021-94324-z · Cited by 39 · see citing works
Hafez, H. A., Kamel, M. A. E.-N., Osman, M. Y. H., Osman, H., Elblehi, S. S., & Mahmoud, S. A. (2021) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-021-04079-4 · Cited by 42 · see citing works
Origins of lymphocyte developmental programs: transcription factor evidence
Rothenberg, E. V., & Pant, R. (2004) · Seminars in Immunology · doi:10.1016/j.smim.2004.08.002 · Cited by 42 · see citing works
Quantitative Proteomic Characterization of Ethanol-Responsive Pathways in Rat Microglial Cells
Bell‐Temin, H., Zhang, P., Chaput, D., King, M. A., You, M., Liu, B., & Stevens, S. M. (2013) · Journal of Proteome Research · doi:10.1021/pr301038f · Cited by 41 · see citing works
López‐Rodríguez, C., & Corbí, A. L. (1997) · European Journal of Immunology · doi:10.1002/eji.1830270804 · Cited by 36 · see citing works
Bush, S. J., Freem, L. J., MacCallum, A. J., O’Dell, J., Wu, C., Afrasiabi, C., Psifidi, A., Stevens, M. P., Smith, J., SUMMERS, K. M., et al. (2018) · BMC Genomics · doi:10.1186/s12864-018-4972-7 · Cited by 39 · see citing works
IL‐4 blocks M‐CSF‐dependent macrophage proliferation by inducing p21Waf1 in a STAT6‐dependent way
Arpa, L., Valledor, A. F., Lloberas, J., & Celada, A. (2009) · European Journal of Immunology · doi:10.1002/eji.200838283 · Cited by 39 · see citing works
Self-citationProtein Acetylation Regulates Both PU.1 Transactivation and Igκ 3′ Enhancer Activity
Bai, Y., Srinivasan, L., Perkins, L., & Atchison, M. L. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.8.5160 · Cited by 38 · see citing works
Choe, K., Ujhelly, O., Wontakal, S. N., & Skoultchi, A. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.077727 · Cited by 31 · see citing works
Hematopoietic stem cells and retroviral infection
Banerjee, P., Crawford, L. B., Samuelson, E., & Feuer, G. (2010) · Retrovirology · doi:10.1186/1742-4690-7-8 · Cited by 38 · see citing works
“1 expression results not only in the loss of B-cells and macrophage development, but also delays T lymphopoiesis [143,144].”
BackgroundIglesias–Ara, A., Zenarruzabeitia, O., Fernández‐Rueda, J., Sànchez‐Tilló, E., Field, S. J., Celada, A., & Zubiaga, A. M. (2010) · Oncogene · doi:10.1038/onc.2010.296 · Cited by 31 · see citing works
Self-citationPascual-García, M., Carbo, J. M. C. I., León, T. E., Matalonga, J., Out, R., van Berkel, T. J. C., Sarrias, M., Lozano, F., Celada, A., & Valledor, A. F. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1000585 · Cited by 32 · see citing works
“Cell proliferation was measured as previously described (31), with minor modifications.”
MethodSelf-citationETS Transcription Factors in Immune Cells and Immune-Related Diseases
Yang, Y., Han, X., Sun, L., Shao, F., Yin, Y., & Zhang, W. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251810004 · Cited by 34 · see citing works
Taming of macrophage and microglial cell activation by microRNA-124
Conrad, A., & Dittel, B. N. (2011) · Cell Research · doi:10.1038/cr.2011.9 · Cited by 29 · see citing works
Sànchez‐Tilló, E., Comalada, M., Farrera, C., Valledor, A. F., Lloberas, J., & Celada, A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.11.6594 · Cited by 30 · see citing works
“siRNA were obtained from Dharmacon and transfected by electroporation (31).”
Self-citationGuerrero‐Carrasco, M., Targett, I. L., Olmos‐Alonso, A., Vargas‐Caballero, M., & Gómez‐Nicola, D. (2024) · Glia · doi:10.1002/glia.24532 · Cited by 26 · see citing works
“Research using hematopoietic stem cells has shown that inflammatory cytokines, such as IL-1 β and TNF α , can upregulate the expression of Pu.1 (Etzrodt et al., 2019), a transcription factor that can control microglial proliferation by stimulating Csf1r expression (Celada et al., 1996).”
BackgroundPhosphatidylinositol 4-phosphatase type II is an erythropoietin-responsive gene
Barnache, S., Scolan, E. L., Kosmider, O., Denis, N., & Moreau-Gachelin, F. (2005) · Oncogene · doi:10.1038/sj.onc.1209187 · Cited by 26 · see citing works
“Spi-1/PU.1 is a master gene in the development of B lymphoid, monocyte and neutrophilic lineages (Scott et al., 1994; Celada et al., 1996; Oikawa et al., 1999).”
BackgroundPU.1 as a chromatin accessibility factor for immunoglobulin genes
Marecki, S., McCarthy, K. M., & Nikolajczyk, B. S. (2004) · Molecular Immunology · doi:10.1016/j.molimm.2003.08.007 · Cited by 25 · see citing works
Macrophage inflammation resolution requires CPEB4-directed offsetting of mRNA degradation
Suñer, C., Sibilio, A., Martín, J., et al. (2022) · eLife · doi:10.7554/elife.75873 · Cited by 24 · see citing works
Comalada, M., Valledor, A. F., Sànchez‐Tilló, E., Umbert, I. J., Xaus, J., & Celada, A. (2003) · European Journal of Immunology · doi:10.1002/eji.200324074 · Cited by 24 · see citing works
Self-citationThe Exercise Training Modulatory Effects on the Obesity-Induced Immunometabolic Dysfunctions
Soltani, N., Marandi, S. M., Kazemi, M., & Esmaeil, N. (2020) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s234992 · Cited by 24 · see citing works
“MФs, then, possess a larger periphery, longer lifetime (up to several months), and more phagocytic features than MONs.69 Nevertheless, MONs which do not migrate into the tissues (in order not to participate in an immunity response) will die after these few days.37 They initially act as environmental sensors and also p…”
BackgroundPU.1 Regulates Cathepsin S Expression in Large Yellow Croaker (Larimichthys crocea) Macrophages
Zhang, X.-Y., Zhuo, X., Cheng, J., Wang, X., Liang, K., & Chen, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.819029 · Cited by 21 · see citing works
“The transactivation domain is required for the M-CSF-dependent proliferation of macrophages (23).”
BackgroundInfluentialHematopoietic Stem Cell Molecular Targets and Factors Essential for Hematopoiesis
Raghav, P. K., & Gangenahalli, G. U. (2018) · Journal of Stem Cell Research & Therapy · doi:10.4172/2157-7633.1000441 · Cited by 21 · see citing works
“In the PEST domain, residues 41 and 45 are essential for the enhancement of macrophage proliferation [50].”
Background
- Authors
- Celada, A., Borràs, F. E., Soler, C., Lloberas, J., Klemsz, M., van Beveren, C., McKercher, S., & Maki, R. A.
- Affiliations
- Universitat de Barcelona (ES)
- Departament de Fisiologia (Immunologia), Facultat de Biologia, Universitat de Barcelona, Spain.
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1996-07-01
- Volume
- 184
- Issue
- 1
- Pages
- 61-69
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2192661
- OpenAlex
- W1972310581
- Cited by
- 161
- References
- 59
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 7 · 2023: 3 · 2022: 14 · 2021: 5 · 2020: 4 · 2019: 1 · 2018: 5 · 2017: 2 · 2016: 1 · 2015: 6 · 2014: 1 · 2013: 7
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-sa)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- PU.1, macrophage proliferation, macrophage colony-stimulating factor, M-CSF receptor, transcription factors, ETS family, ETS2, FLI1
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Base Sequence, Bone Marrow Cells, DNA-Binding Proteins, Gene Expression Regulation, Macrophage Activation, Macrophages, Mice, Inbred DBA
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