The DOI matches its Crossref record; 88 of the 90 references it cites were found in a registry or an index; 10 of the 29 sources its claims cite were checked for support.
Multiple Functional Domains of AML1: PU.1 and C/EBPα Synergize with Different Regions of AML1
Open accessAbstract
Control elements of many genes are regulated by multiple activators working in concert to confer the maximal level of expression, but the mechanism of such synergy is not completely understood. The promoter of the human macrophage colony-stimulating factor (M-CSF) receptor presents an excellent model with which we can study synergistic, tissue-specific activation for two reasons. First, myeloid-specific expression of the M-CSF receptor is regulated transcriptionally by three factors which are crucial for normal hematopoiesis: PU.1, AML1, and C/EBPalpha. Second, these proteins interact in such a way as to demonstrate at least two examples of synergistic activation. We have shown that AML1 and C/EBPalpha activate the M-CSF receptor promoter in a synergistic manner. As we report here, AML1 also synergizes, and interacts physically, with PU. 1. Detailed analysis of the physical and functional interaction of AML1 with PU.1 and C/EBPalpha has revealed that the proteins contact one another through their DNA-binding domains and that AML1 exhibits cooperative DNA binding with C/EBPalpha but not with PU.1. This difference in DNA-binding abilities may explain, in part, the differences observed in synergistic activation. Furthermore, the activation domains of all three factors are required for synergistic activation, and the region of AML1 required for synergy with PU.1 is distinct from that required for synergy with C/EBPalpha. These observations present the possibility that synergistic activation is mediated by secondary proteins contacted through the activation domains of AML1, C/EBPalpha, and PU.1.
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Claims the paper makes
10 of 29 cited sources checked · 5 supported · 1 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“demonstrated that mutations in any of the three DNA-binding sites decreases promoter activity significantly in transient transfection studies (77)(78)(79).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Abstract
What the sources say
- Not checked — no full text of the sourcecites [77] source
- Partly supportedcites [78] sourceExperimental — accuracy not yet measured
The Results (Fig. 7) report that mutating the PU.1 site reduced M-CSF receptor promoter activity to 16% of wild type in transiently transfected U937 cells. The supplied passages do not establish the claimed effects of disrupting C/EBPα or AML1 sites; this paper supports the PU.1 portion of the statement. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [79] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“it synergizes with AML1B to increase the activity of the promoter an average of 90-fold (78,79).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Abstract
What the sources say
- Could not verifycites [78] sourceExperimental — accuracy not yet measured
The Results report M-CSF receptor promoter activity and a fivefold increase with PU.1 in HeLa cells, but do not address C/EBPα paired with AML1B. Searches for AML1B, C/EBP and a 90-fold increase found no passage supporting the attributed synergy or magnitude. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites [79] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“The production of C/EBP␣ protein from these constructs has been demonstrated previously by Western blot analysis of extracts from transfected HepG2 cells (17).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Synergy between AML1B and C/EBP␣ requires their transactivation domains, and the region of AML1 critical for this synergy is distinct from that important for synergy with PU.1.
What the sources say
- Supportedcites [17] source
In “A discrete activation element is located close to the amino terminus of C/EBP,” the authors report Western blotting of extracts from HepG2 cells transfected with C/EBP expression vectors and detection of protein from multiple variants. In “The central region of C/EBP contains a redundant set of activating elements,” they report that Western blotting showed expression of all 13 additional variants. No page numbers are available in our copy. (LLM, conf=0.88)
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“a region important for synergy between AML1 and c-Myb (6)”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
What the sources say
- Partly supportedcites [6] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) identifies AML-1B regions 216–289 and 278–480 as required for optimal cooperation with c-Myb, while saying its DNA-binding domain is dispensable. This supports the importance of part of amino acids 1–317, but not that the specified 1–317 region as a whole is the region required for synergy; the paper also identifies a required segment extending beyond residue 317. (LLM, conf=0.85)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A ternary complex containing both proteins and the oligonucleotide was also observed (lane 4).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AML1 also synergizes, and interacts physically, with PU.1.”
- Also stated in: § RESULTS · boosted
“these data demonstrate that AML1 and PU.1 interact physically”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these data demonstrate that AML1-C/EBP and AML1-PU.1 DNA-protein ternary complexes can be detected with purified proteins.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We have also established that the interaction between PU.1 and the runt domain of AML1 localizes to the DNA-binding ets domain of PU.1.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the proteins contact one another through their DNA-binding domains”
- Also stated in: § RESULTS · plain
“this interaction occurs primarily through their DNA-binding domains.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“radiolabeled, in vitro-translated AML1 interacts with a GST fusion protein containing full-length PU.1.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 9
- It may state two separate claims as one. 36
- The quote only partly states this claim. 2
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“The activation of an AML1-responsive reporter by AML1A can be increased following phosphorylation by ERK on serines 249 and 266 (corresponding to serines 276 and 293 of AML1B) (68).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Mutation of potential phosphorylation sites in AML1 does not interfere with synergistic activation of the M-CSF receptor promoter.
What the sources say
- Disputedcites [68] sourceExperimental — accuracy not yet measured
The Results (Fig. 2) identify the protein carrying the ERK-dependent sites as AML1b and state that AML1a lacks the PST region; no ERK-dependent phosphorylation shift was detected for AML1a. The Results (Fig. 3) assign the sites to AML1b serines 249 and 266 and say that its serine 276 was not a detectable ERK-dependent phosphorylation site. The reporter increase described in the Results (Fig. 8) therefore supports the effect for AML1b, not the isoform and residue mapping in the claim. (LLM, conf=0.91)
Checked by a reasoning model — may be wrong.
Strength:plain· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“CBP is a ubiquitous adapter protein that mediates contacts between transcription factors and the basal transcription machinery (1,26,33) and is thought to stimulate transcription both by physical contact with the RNA polymerase II complex and through intrinsic histone acetylation activity (4, 33, 52).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [1] source
- Not checked — no full text of the sourcecites [26] source
- Partly supportedcites [33] sourceExperimental — accuracy not yet measured
The discussion reports that CBP interacts with the basal transcription factor TFIIB, supporting the proposed link between transcription factors and basal machinery; the paper primarily investigates this bridging role in p300. Our copy does not establish that CBP is ubiquitous or that it stimulates transcription through contact with the RNA polymerase II complex or intrinsic histone acetylation. The indexed passages provide no page number. (LLM, conf=0.88)
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“In several studies, the physical interaction between transcription factors increases DNA-binding ability, providing an explanation for synergistic activation in the presence of two factors (11,18,56,58,67).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
What the sources say
- Supportedcites [11] source
The “DNA binding by Pip” section reports that Pip binds DNA only when PU.1 is bound nearby and proposes that their interaction enables Pip to bind. The “In conjunction with PU.1” section reports that neither factor alone activated the reporter, whereas the two together did. These passages support this paper as an example of the proposed mechanism; page numbers are unavailable in our copy. (LLM, conf=0.91)
- Supportedcites [18] source
The Discussion (page not available in our copy) links cooperative DNA binding by PEBP2a and Ets-1 to synergistic activation of the TCRα enhancer. The paper also reports that PEBP2a augments Ets-1 DNA binding, supporting the proposed explanation for synergy. (LLM, conf=0.92)
- Supportedcites [56] source
The paper’s introductory text (page not available in our copy) states that protein–protein interaction with PU.1 is required to recruit PIP to DNA. The Results report cooperative PU.1–PIP DNA binding, and the paper reports synergistic transcription when enhancer-binding factors are combined. This supports the cited paper as an example of the proposed explanation, rather than as evidence that all transcription-factor pairs behave this way. (LLM, conf=0.90)
Strength:plain· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Although AML1 is known to interact with Ets-1, which like PU.1 is a member of the ets family of transcription factors, in this situation it is not the conserved ets DNA-binding domain which makes contact with the runt domain of AML1, but rather amino acids 123 to 240 in the N terminus of Ets-1 (18).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
What the sources say
- Supportedcites [18] source
In the section on PEBP2a recruitment of Ets-1 (page not available), the paper reports an in vitro association between the PEBP2a Runt domain and Ets-1. Deletion experiments place the interacting region of Ets-1 between amino acids 123 and 240, supporting the claim that contact is through this region rather than the Ets DNA-binding domain. (LLM, conf=0.90)
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Transfections of HeLa cells, which contain no endogenous PU.1 and little detectable AML1, showed that while PU.1 activates the promoter 2-fold and AML1B 3.5-fold, together they synergize to increase the activity of the promoter 12-fold (Fig. 5A).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > PU.1 and AML1 synergize to activate the M-CSF receptor promoter, a function which is dependent on regions within the activation domains of PU.1 and AML1B.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: HeLa cells lack endogenous PU.1 and have only low detectable AML1.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“purified GST-PU.1 (lane 2) and GST-runt, a fusion protein containing the runt domain of AML1 (79) (lane 3), bound to the radiolabeled oligonucleotide which contains the M-CSF receptor promoter AML1 and PU.1 sites”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we show that, in addition to C/EBP␣, AML1B interacts with PU.1 to synergistically activate the M-CSF receptor promoter but requires different regions contained within the C terminus for each function.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both the 250 (Fig. 4A, lanes 1 and 5)-and 479 (lanes 2 and 8)-amino-acid forms (AML1 and AML1B [Fig.1]) are pulled down by GST-PU.1;however, the interaction with AML1B appears stronger.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AML1 exhibits cooperative DNA binding with C/EBP␣ but not with PU.1.”
- Also stated in: § RESULTS · plain
“while the runt domain of AML1 binds cooperatively to DNA in the presence of the C/EBP␣ bZip domain, the ternary complex with PU.1 is formed in a noncooperative manner.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we detected more DNA associated with the higher-order complex formed in the presence of the AML1 runt domain (lanes 10 to 18) than with GST-bZip (lanes 1 to 9), providing evidence that AML1 and C/EBP␣ exhibit cooperative DNA binding.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“deletion of the PEST domain, which is important for interaction with NF-EM5 and activation of Bcell genes (58), has no effect on activation of the M-CSF receptor promoter or synergy with AML1B.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > PU.1 and AML1 synergize to activate the M-CSF receptor promoter, a function which is dependent on regions within the activation domains of PU.1 and AML1B.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the amount of probe shifted by the higher-order complex is less than that shifted by either GST-runt (data not shown) or GST-PU.1,indicating that AML1 and PU.1 do not bind cooperatively to DNA.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > RESULTS
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, deletion of amino acids 1 to 70 or 33 to 100 abrogates synergy, indicating that amino acids 33 to 70 of the PU.1 activation domain are important for this function.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > PU.1 and AML1 synergize to activate the M-CSF receptor promoter, a function which is dependent on regions within the activation domains of PU.1 and AML1B.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“full-length PU.1 (lanes 1 and 7) and amino acids 161 to 272 containing the ets domain of PU.1 (lanes 2 and 10), but not the activation domain of PU.1 (amino acids 1 to 161 [lanes 3 and 13]), interact specifically with the GST fusion protein containing the AML1 runt domain.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While termination of AML1B at amino acid 381 does not affect synergistic activation of the promoter, termination at amino acid 317 clearly does.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > PU.1 and AML1 synergize to activate the M-CSF receptor promoter, a function which is dependent on regions within the activation domains of PU.1 and AML1B.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the synergy between PU.1 and AML1B is weak relative to that observed with AML1B and C/EBP␣, it is more than an additive effect.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > PU.1 and AML1 synergize to activate the M-CSF receptor promoter, a function which is dependent on regions within the activation domains of PU.1 and AML1B.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, this synergy is absent with reporter constructs bearing mutations in either the PU.1 or AML1 binding site [pM-CSF-R(mPU.1)-lucor pM-CSF-R(mAML1)luc, respectively] or a deletion of bp Ϫ86 to Ϫ37 [pM-CSF-R(DD)-luc], containing the binding sites for C/EBP, AML1, and PU.1, indicating that DNA binding is required for both factors.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > PU.1 and AML1 synergize to activate the M-CSF receptor promoter, a function which is dependent on regions within the activation domains of PU.1 and AML1B.
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: HeLa cells lack endogenous PU.1 and have only low detectable AML1.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these data demonstrate that AML1 and PU.1 interact physically and that this interaction occurs primarily through their DNA-binding domains.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in HeLa cells AML1B(1-289) and -(1-317) activate the M-CSF receptor promoter 3.5-and 3.8fold, respectively, relative to the expression vector, pCMV5, and both of these proteins are capable of synergizing with C/EBP␣ (Fig. 6A).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > PU.1 and AML1 synergize to activate the M-CSF receptor promoter, a function which is dependent on regions within the activation domains of PU.1 and AML1B.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: HeLa cells lack endogenous PU.1 and have only low detectable AML1.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The formation of this PU.1-runtcomplex could be competed with a 200-fold molar excess of unlabeled self oligonucleotide (lane 5) or an oligonucleotide containing either a PU.1 binding site (lane 7) or an AML1 binding site (lane 8) but not with a nonspecific C/EBP-binding oligonucleotide (lane 6).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AML1B truncated at either amino acid 317 or 289 retains the ability to synergize with C/EBP␣ (represented by the fold synergy), indicating that amino acids 268 to 317 are important for this activity.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Synergy between AML1B and C/EBP␣ requires their transactivation domains, and the region of AML1 critical for this synergy is distinct from that important for synergy with PU.1.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The results of these experiments show that amino acids 268 to 317 of AML1B, and the transactivation domains of C/EBP␣, are critical for synergy.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Synergy between AML1B and C/EBP␣ requires their transactivation domains, and the region of AML1 critical for this synergy is distinct from that important for synergy with PU.1.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Synergy between AML1B and C/EBP␣ requires their transactivation domains, and the region of AML1 critical for this synergy is distinct from that important for synergy with PU.1.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Synergy between AML1B and C/EBP␣ requires their transactivation domains, and the region of AML1 critical for this synergy is distinct from that important for synergy with PU.1.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 250-amino-acid isoform, AML1, which effectively terminates at residue 268 of AML1B, does not synergize with C/EBP␣, nor does AML1B truncated at amino acid 268.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Synergy between AML1B and C/EBP␣ requires their transactivation domains, and the region of AML1 critical for this synergy is distinct from that important for synergy with PU.1.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data demonstrate that AML1 synergizes with PU.1 to activate the M-CSF receptor promoter and that this activity requires DNA-binding sites for both factors and regions contained within the activation domains of AML1 and PU.1.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > PU.1 and AML1 synergize to activate the M-CSF receptor promoter, a function which is dependent on regions within the activation domains of PU.1 and AML1B.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Wild-type AML1A and mutant S249A/S266A both synergize with C/EBP␣.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“amino acids 1 to 317, a region important for synergy between AML1 and c-Myb (6), are sufficient for synergy with C/EBP␣ but not PU.1.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“while the 250-amino-acid form of AML1 contains the runt domain, there is no synergy observed with either PU.1 or C/EBP␣.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AML1 forms a tertiary complex on DNA with PU.1 but does not exhibit cooperative DNA binding.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we are able to show that TBP binds to a fusion protein containing the region of AML1B important for synergy with C/EBP␣ but not to a portion that contains the domain required for synergy with PU.1 (data not shown).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“the activation of the reporter construct by the AML1B mutants indicates that they are expressed, are transported to the nucleus, and are capable of binding the promoter.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > PU.1 and AML1 synergize to activate the M-CSF receptor promoter, a function which is dependent on regions within the activation domains of PU.1 and AML1B.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“EMSA analysis of COS cell extracts transfected with the PU.1 expression constructs demonstrated that the mutated proteins were produced in comparable amounts and are capable of binding to DNA (data not shown).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > PU.1 and AML1 synergize to activate the M-CSF receptor promoter, a function which is dependent on regions within the activation domains of PU.1 and AML1B.
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, while in the case of AML1 and C/EBP␣, the physical interactions may contribute to co- operative DNA binding, this is not sufficient for the strong synergy.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“confirming that the C-terminal domains of AML1B make specific and distinct contacts, any of which may play a role in synergistic activation.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The functional variability of AML1 can be explained if it requires contacts with other factors to activate transcription and is accordingly dependent on the cell type as well as other DNA-binding sites.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Kamei et al. have coined the term “integrator,” postulating that CBP integrates diverse signals within the cell which culminate in the assembly of transcription factors and coactivators and translates them into transcriptional activation (26).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [26] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For instance, the ability for AML1 to synergize with PU.1 or C/EBP␣ or to coordinate the actions of all three transcription factors may depend on the activation or availability of coactivators and integrators.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Recent reports have revealed a complex mechanism, whereby nuclear hormone receptors are associated with both steroid receptor coactivators and with CBP, and the activation ability of the transcription factor is dependent on the efficient assembly of these complexes on the DNA (43).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [43] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“We have previously shown that AML1B and C/EBP␣ synergize to activate the M-CSF receptor promoter, that both DNAbinding sites are required for this function, and that the factors interact in vitro via their DNA-binding domains (runt and bZip domains, respectively) (79).”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > Synergy between AML1B and C/EBP␣ requires their transactivation domains, and the region of AML1 critical for this synergy is distinct from that important for synergy with PU.1.
What the sources say
- Not checked — no full text of the sourcecites [79] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“A similar mechanism has been described for the DNA-binding nuclear hormone receptors.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [43] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The carboxy terminus of AML1B contains at least two domains that serve disparate functions, each of which is responsible for synergy with C/EBP␣ and PU.1.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, since these experiments were performed with the DNA-binding domains of AML1 and C/EBP␣, we cannot exclude the possibility that the native pro-teins would exhibit different properties.”
§ Multiple Functional Domains of AML1: PU.1 and C/EBP␣ Synergize with Different Regions of AML1 > DISCUSSION
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
HeLa cells lack endogenous PU.1 and have only low detectable AML1.
“Transfections of HeLa cells, which contain no endogenous PU.1 and little detectable AML1”
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“(RUNX factors alone are relatively weak activators of transcription.4,5,7,8,11)”
From RUNX1 regulates corepressor interactions of PU.1 (2011) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“RUNX1 physically interacts with PU.1, CEBPA, GATA1, GATA2, PAX5, FLI1, and ETS1.4–10,13”
From RUNX1 regulates corepressor interactions of PU.1 (2011) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“RUNX1 synergistically increases transcriptional activation by ETS1, PU.1(SPI1), CCAAT/enhancer binding protein-α (CEBPA), GATA1, GATA2, and FLI1.4–10”
From RUNX1 regulates corepressor interactions of PU.1 (2011) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The transcription factor (TF) RUNX1 cooperates with lineage-specifying TFs (eg, PU.1/SPI1) to activate myeloid differentiation genes, such as macrophage and granulocyte macrophage colony-stimulating factor receptors (MCSFR and GMCSFR).”
From RUNX1 regulates corepressor interactions of PU.1 (2011) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In cotransfection experiments, RUNX1, PU.1, and CEBPA play essential roles in activation of the hematopoietic differentiation genes MCSFR and GMCSFR.7,8,31”
From RUNX1 regulates corepressor interactions of PU.1 (2011) · cites this paper as [8]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“Loss of this function of the RUNX1 C-terminus could contribute to the inability of RUNT to synergize with PU.1 to transactivate the MCSFR promoter,8 and the impaired differentiation and leukemogenesis associated with expression of RUNX1a (a RUNX1 isoform that lacks the RUNX1 C-terminus).38,39”
From RUNX1 regulates corepressor interactions of PU.1 (2011) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“In keeping with this paradigm, RUNX1 alone is a relatively weak activator of transcription.4,5,7,8,11”
From RUNX1 regulates corepressor interactions of PU.1 (2011) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“However, RUNX1 potently enhances gene activation by multiple key hematopoietic lineage-specifying TFs.4–10”
From RUNX1 regulates corepressor interactions of PU.1 (2011) · cites this paper as [8]
In the citing paper
“The myeloid-specific expression of the neutrophil elastase, 58 M-CSF receptor, 29,30 and myeloperoxidase 27 is mainly controlled through the concerted and synergistic action of RUNX1 with factors such as Myb, PU.1, and C/EBP, which bind closely located elements on their respective promoter regions.”
From RUNX/AML and C/EBP factors regulate CD11a integrin expression in myeloid cells through overlapping regulatory elements. (2003) · cites this paper as [29]
In the citing paper
“The role of the DNA-binding proteins is to confer tissue-specific, temporal regulation, whereas the co-activators (such as CBF-β) serve to amplify the activation by increasing transcription efficiency [32].”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [32]
In the citing paper
“During monocytic commitment and differentiation, AML-1B regulates the myeloid-specific expression of M-CSF receptor in synergistic association with C/EBP-α and PU.1 by forming a ternary complex on DNA [32] (Fig. 7).”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [32]
In the citing paper
“Although AML-1 and PU.1 exhibit a relatively weak synergistic activation of the promoter, but because the effect seen in the presence of both PU.1 and AML-1 is more than additive, the interaction is defined as synergistic [32].”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [32]
In the citing paper
“The DNA-binding domain of PU.1 has been found to interact physically with many proteins, including myeloid regulators such as AML-1B and C/EBPα (3, 19).”
From Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1 (1999) · cites this paper as [19]
In the citing paper
“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 [19]
In the citing paper
“RUNX1 by itself is a weak activator of transcription”
From Runx1 regulation of Pu.1 corepressor/coactivator exchange identifies specific molecular targets for leukemia differentiation therapy (2014) · cites this paper as [10]
In the citing paper
“RUNX1 synergistically augments transcription activation by multiple hematopoietic lineage specifying transcription factors: PU.1, CEBPA, ETS1, GATA1, GATA2, FLI1, PAX5, SCL, and ERG”
From Runx1 regulation of Pu.1 corepressor/coactivator exchange identifies specific molecular targets for leukemia differentiation therapy (2014) · cites this paper as [10]
In the citing paper
“PU.1-Ets can recruit c-Jun”
From Molecular Analysis of the Interaction between the Hematopoietic Master Transcription Factors GATA-1 and PU.1 (2006) · cites this paper as [21]
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.
Aligned AML1 regions differ by one residue in length
MinorThe two regions described as identical contain different numbers of residues when both endpoints are included: AML1 residues 5-242 span 238 residues, while AML1B residues 32-268 span 237.
“AML1 contains 250 amino acids and is identical to AML1B from amino acid 5 to 242”
“(32 to 268 of AML1B)”
PU.1 mutant has two reported endpoints
MinorThe Results describe the PU.1 activation-domain construct in Figure 4C as ending at amino acid 161, but the figure caption identifies that construct as ending at amino acid 163.
“the activation domain of PU.1 (amino acids 1 to 161 [lanes 3 and 13])”
“amino acids 1 to 163 of PU.1 (lanes 3 and 11 to 13)”
Citations
Cites
Smith, D. B., & Johnson, K. S. (1988) · Gene · doi:10.1016/0378-1119(88)90005-4 · Cited by 5,844
The Leucine Zipper: A Hypothetical Structure Common to a New Class of DNA Binding Proteins
Landschulz, W. H., Johnson, P. F., & McKnight, S. L. (1988) · Science · doi:10.1126/science.3289117 · Cited by 3,443
The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases
Ogryzko, V. V., Schiltz, R. L., Russanova, V., Howard, B. H., & Nakatani, Y. (1996) · Cell · doi:10.1016/s0092-8674(00)82001-2 · Cited by 2,952
Kamei, Y., Xu, L., Heinzel, T., Torchia, J., Kurokawa, R., Gloss, B., Lin, S.-C., Heyman, R. A., Rose, D. W., Glass, C. K., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81118-6 · Cited by 2,150
Okuda, T., van Deursen, J., Hiebert, S. W., Grosveld, G., & Downing, J. R. (1996) · Cell · doi:10.1016/s0092-8674(00)80986-1 · Cited by 1,856
Self-citationThe CBP co-activator is a histone acetyltransferase
Bannister, A. J., & Kouzarides, T. (1996) · Nature · doi:10.1038/384641a0 · Cited by 1,828
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
Wang, Q., Stacy, T., Binder, M., Marin-Padilla, M., Sharpe, A. H., & Speck, N. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3444 · Cited by 1,178
Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities
McKercher, S. R., Torbett, B. E., Anderson, K. L., Henkel, G. W., Vestal, D. J., Baribault, H., Klemsz, M., Feeney, A. J., Wu, G. E., Paige, C. J., et al. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00949.x · Cited by 1,130
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
Flagged first, then by citations
2 of the 90 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Core-binding factors in haematopoiesis and leukaemia
Speck, N. A., & Gilliland, D. G. (2002) · Nature reviews. Cancer · doi:10.1038/nrc840 · Cited by 575
Role of RUNX1 in hematological malignancies
Sood, R. B., Kamikubo, Y., & Liu, P. (2017) · Blood · doi:10.1182/blood-2016-10-687830 · Cited by 509
Zhang, P., Iwasaki-Arai, J., Iwasaki, H., Fenyus, M. L., Dayaram, T., Owens, B. M., Shigematsu, H., Levantini, E., Huettner, C. S., Lekstrom-Himes, J. A., et al. (2004) · Immunity · doi:10.1016/j.immuni.2004.11.006 · Cited by 526
Self-citationGelmetti, V., Zhang, J., Fanelli, M., Minucci, S., Pelicci, P. G., & Lazar, M. A. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.12.7185 · Cited by 492
Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1
Zhang, P., Behre, G., Pan, J., Iwama, A., Wara-aswapati, N., Radomska, H. S., Auron, P. E., Tenen, D. G., & Sun, Z. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.15.8705 · Cited by 459
Self-citationRekhtman, N., Radparvar, F., Evans, T., & Skoultchi, A. I. (1999) · Genes & Development · doi:10.1101/gad.13.11.1398 · Cited by 454
“Certain interactions of PU.1 with other proteins are mediated by the transactivation domain (Hagemeir et al. 1993), whereas other interactions occur with the Ets domain (Nagulapalli et al. 1995; Petrovick et al. 1998).”
BackgroundAML1–ETO downregulates the granulocytic differentiation factor C/EBPα in t(8;21) myeloid leukemia
Pabst, T., Mueller, B. U., Harakawa, N., Schoch, C., Haferlach, T., Behre, G., Hiddemann, W., Zhang, D.-E., & Tenen, D. G. (2001) · Nature Medicine · doi:10.1038/86515 · Cited by 463
“We show that in RUNX1–CBF2T1 leukemia patient samples as well as in cell lines derived from patients with the t(8;21) alteration, C/EBPα is undetectable.”
BackgroundMethodInfluentialSelf-citationPU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding
Zhang, P., Zhang, X., Iwama, A., Yu, C., Smith, K. A., Mueller, B. U., Narravula, S., Torbett, B. E., Orkin, S. H., & Tenen, D. G. (2000) · Blood · doi:10.1182/blood.v96.8.2641 · Cited by 368
Self-citationTranscriptional regulation of granulocyte and monocyte development
Friedman, A. D. (2002) · Oncogene · doi:10.1038/sj.onc.1205324 · Cited by 333
“In immature 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.,…”
BackgroundSelf-citationTahirov, T. H., Inoue-Bungo, T., Morii, H., Fujikawa, A., Sasaki, M., Kimura, K., Shiina, M., Sato, K., Kumasaka, T., Yamamoto, M., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00271-9 · Cited by 329
“…protein–protein and protein–DNA bindingin segmentation, sex determination, and neurogenesis, and Lozenge, which is involved in eye development (Ka- assays (Zhang et al., 1996; Petrovick et al., 1998), analyses of crystals of the CBFa-b-C/EBPb-DNA and CBFa-goshima et al., 1993, 1996; Ito, 1999).”
BackgroundOncogenic potential of the RUNX gene family: ‘Overview’
Ito, Y. (2004) · Oncogene · doi:10.1038/sj.onc.1207755 · Cited by 318
“References for interacting proteins: ALY (Bruhn et al., 1997), SUV39H1 (Chakraborty et al., 2003), AP-1 (Hess et al., 2001), binding to DNA and PEBP2b/ CBFb (Kagoshima et al., 1996), ETS-1 (Kim et al., 1999), MOZ (Kitabayashi et al., 2001), p300 (Kitabayashi et al., 1998), LEF-1 (Li FQ et al., 2004), PAX5 (Libermann e…”
The 8;21 translocation in leukemogenesis
Peterson, L. F., & Zhang, D. (2004) · Oncogene · doi:10.1038/sj.onc.1207727 · Cited by 304
“Furthermore, AML1 can synergize or collaborate with C/EBPa and PU.1 in the activation of M-CSF receptor promoter (Zhang et al., 1996; Petrovick et al., 1998).”
BackgroundSelf-citationWestendorf, J. J., Yamamoto, C. M., Lenny, N., Downing, J. R., Selsted, M. E., & Hiebert, S. W. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.1.322 · Cited by 270
Self-citationc-Myc Is a Critical Target for C/EBPα in Granulopoiesis
Johansen, L. M., Iwama, A., Lodie, T. A., Sasaki, K., Felsher, D. W., Golub, T. R., & Tenen, D. G. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.11.3789-3806.2001 · Cited by 263
“DP1) and GST-E2F1 were a gift of S. Chellappan and are described in reference 70. Other GST fusion proteins have previously been described ( 51 ).”
BackgroundSelf-citationGutierrez, S. E., Javed, A., Tennant, D. K., van Rees, M., Montecino, M. A., Stein, G. S., Stein, J. L., & Lian, J. B. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m106611200 · Cited by 251
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
Self-citationLutterbach, B. A., Westendorf, J. J., Linggi, B. E., Isaac, S., Seto, E., & Hiebert, S. W. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.651 · Cited by 245
Self-citationIL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells
Lee, J., Chung, H. Y., Ehrlich, L. A., Jelinek, D. F., Callander, N. S., Roodman, G. D., & Choi, S. J. (2003) · Blood · doi:10.1182/blood-2003-06-1992 · Cited by 235
Javed, A., Guo, B., Hiebert, S. W., Choi, J., Green, J., Zhao, S.-C., Osborne, M. A., Stifani, S., Stein, J. L., Lian, J. B., et al. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.12.2221 · Cited by 233
Self-citationIdentification and characterization of Hoxa9 binding sites in hematopoietic cells
Huang, Y., Sitwala, K. V., Bronstein, J. C., Sanders, D. S., Dandekar, M., Collins, C. T., Robertson, G., MacDonald, J. W., Cezard, T., Bilenky, M., et al. (2011) · Blood · doi:10.1182/blood-2011-03-341081 · Cited by 202
Downing, J. R. (1999) · British Journal of Haematology · doi:10.1046/j.1365-2141.1999.01377.x · Cited by 214
“In support of this interpretation, AML1 has been shown to synergistically activate transcription of the TCRb and TCRa enhancers with Ets1 (Giese et al, 1995; Sun et al, 1995), the NP-3 promoter with C/EBP-a (Westerdorf et al, 1998) and the CSF-1R promoter with both C/EBP-a and PU.1 (Petrovick et al, 1998).”
BackgroundRole of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation
Lutterbach, B. A., & Hiebert, S. W. (2000) · Gene · doi:10.1016/s0378-1119(00)00014-7 · Cited by 213
Self-citationUpstream and downstream targets of RUNX proteins
Otto, F., Lübbert, M., & Stock, M. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10491 · Cited by 202
“…at target promoters has also been described for the transcription factors c/EBPalpha, c/EBPbeta, c/EBPdelta, ets-1, MEF, PAX5 and Mi through physical interaction [Wotton et al., 1994; Petrovick et al., 1998; Libermann et al., 1999; Mao et al., 1999; Morii et al., 1999; Gutierrez et al., 2002].”
BackgroundHeß, J., Porte, D., Münz, C., & Angel, P. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010601200 · Cited by 188
Role of RUNX family members in transcriptional repression and gene silencing
Durst, K. L., & Hiebert, S. W. (2004) · Oncogene · doi:10.1038/sj.onc.1207122 · Cited by 184
“These factors include C/EBPa (Zhang et al., 1996; Westendorf et al., 1998), ETS family members (Giese et al., 1995; Petrovick et al., 1998; Kim et al., 1999; Mao et al., 1999), SMADs (Hanai et al., 1999; Gu et al., 2000; Jakubowiak et al., 2000; Pardali et al., 2000; Zhang and Derynck, 2000) and…”
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
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
AML1 and the AML1-ETO fusion protein in the pathogenesis of t(8;21) AML
Licht, J. D. (2001) · Oncogene · doi:10.1038/sj.onc.1204593 · Cited by 184
“In contrast PU.1 and AML1 also synergistically activate transcription but bind to each other weakly and do not bind to DNA in a cooperative manner (Petrovick et al., 1998).”
Backgroundc-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 180
Self-citationWang, X., Scott, E., Sawyers, C. L., & Friedman, A. D. (1999) · Blood · doi:10.1182/blood.v94.2.560 · Cited by 166
Self-citationRUNX1 and RUNX1-ETO: roles in hematopoiesis and leukemogenesis
Lam, K. (2011) · Frontiers in bioscience · doi:10.2741/3977 · Cited by 179
“1, C/EBPalpha, p300, mSin3a, GATA1, and Fli1 among many other factors that will not be further discussed in this review (42-47).”
BackgroundReddy, 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
Self-citationGu, T.-L., Goetz, T. L., Graves, B. J., & Speck, N. A. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.1.91-103.2000 · Cited by 150
The 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
Schwieger, M., Löhler, J., Friel, J., Scheller, M., Horak, I. D., & Stocking, C. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020824 · Cited by 143
“Although several myeloid genes are regulated by CBF (6, 7), accumulating evidence suggest that AML1-ETO may exert its effect by protein interaction with other transcription factors, such as PU.1 and C/EBP (18, 19, 64), both of which play a pivotal role in myeloid differentiation, as demonstrated in knock-out mice (66–…”
BackgroundDichotomy of AML1-ETO Functions: Growth Arrest versus Block of Differentiation
Burel, S. A., Harakawa, N., Zhou, L., Pabst, T., Tenen, D. G., & Zhang, D. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.16.5577-5590.2001 · Cited by 142
Self-citationMinderjahn, J., Schmidt, A., Fuchs, A., Schill, R., Raithel, J., Babina, M., Schmidl, C., Gebhard, C., Schmidhofer, S., Mendes, K., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13960-2 · Cited by 136
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 134
Self-citationAuto-Inhibition of Ets-1 Is Counteracted by DNA Binding Cooperativity with Core-Binding Factor α2
Goetz, T. L., Gu, T.-L., Speck, N. A., & Graves, B. J. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.1.81-90.2000 · Cited by 128
“Other ets proteins also synergize with CBFa2 (e.g., Fli-1, PU.1, GABP, and MEF) (38, 52 , 65).”
Aikawa, Y., Nguyen, L. A., Isono, K., Takakura, N., Tagata, Y., Schmitz, M. L., Koseki, H., & Kitabayashi, I. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601273 · Cited by 130
“HIPK2-dependent phosphorylation of p300 is also induced by other transcription factors, such as PU.1, c-MYB, c-JUN and c-FOS, suggesting that the present novel mechanism of transcriptional regulation is of general relevance.”
BackgroundInfluentialCalvo, K. R., Sykes, D. B., Pasillas, M. P., & Kamps, M. P. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.9.3274-3285.2000 · Cited by 128
Gu, X., Ebrahem, Q., Mahfouz, R. Z., Hasipek, M., Enane, F. O., Radivoyevitch, T., Rapin, N., Przychodzen, B. P., Hu, Z., Balusu, R., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97117 · Cited by 118
“CEBPA and RUNX1 are expected to activate granulocytic fates (25, 27); however, the granulocyte differentiation program, like the monocyte differentiation program, is suppressed in AML versus normal granulocytes (Supplemental Figure 11 and Supplemental Table 5).”
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
Origin, development, and homeostasis of tissue‐resident macrophages
Haldar, M., & MURPHY, K. M. M. (2014) · Immunological Reviews · doi:10.1111/imr.12215 · Cited by 125
Andreasson, P., Schwaller, J., Anastasiadou, E., Aster, J. C., & Gilliland, D. G. (2001) · Cancer Genetics and Cytogenetics · doi:10.1016/s0165-4608(01)00518-0 · Cited by 121
Shih, S.-J., Allan, C., Grehan, S., Tse, E., Moran, C., & Taylor, J. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005468200 · Cited by 112
Transcription factor fusions in acute leukemia: variations on a theme
Scandura, J. M., Boccuni, P., Cammenga, J., & Nimer, S. D. (2002) · Oncogene · doi:10.1038/sj.onc.1205315 · Cited by 114
“…PU.1, ETS-1, ELF-1), Smads, and other transcription factors (such as C/EBPa) (Jakubowiak et al., 2000; Kim et al., 1999a,b; Mao et al., 1999; Pardali et al., 2000; Petrovick et al., 1998; Uchida et al., 1997; Wotton et al., 1994; Xie et al., 1999; Zhang et al., 1996b; Zhang and Derynck, 2000).”
BackgroundFujimoto, T., Anderson, K., Jacobsen, S. E. W., Nishikawa, S.-I., & Nerlov, C. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601675 · Cited by 111
“To determine whether Cdk6 directly interfered with any of these factors, we examined the effect of Cdk6 on their ability to activate the macrophagecolony-stimulating factor receptor (M-CSF-R) promoter, which contains collaborating Runx1-, PU.1- and C/EBPabinding sites (Petrovick et al, 1998).”
BackgroundMutations of CEBPA in acute myeloid leukemia FAB types M1 and M2
Snaddon, J., Smith, M. L., Neat, M. J., Cambal‐Parrales, M., Dixon‐McIver, A., Arch, R., Amess, J. A. L., Rohatiner, A. Z. S., Lister, T. A., & Fitzgibbon, J. (2003) · Genes Chromosomes and Cancer · doi:10.1002/gcc.10185 · Cited by 109
“C/EBP is important in the regulation of myeloid differentiation, being expressed particularly in early myeloid cells, in addition to regulating a number of granulocyte-specific genes (Hohaus et al., 1995; Oelgeschlager et al., 1996; Smith et al., 1996; Petrovick et al., 1998).”
BackgroundWarren, A. J., Bravo, J., Williams, R. L., & Rabbitts, T. H. (2000) · The EMBO Journal · doi:10.1093/emboj/19.12.3004 · Cited by 107
RUNX1-targeted therapy for AML expressing somatic or germline mutation in RUNX1
Mill, C. P., Fiskus, W. C., Dinardo, C. D., Qian, Y., Raina, K., Rajapakshe, K., Perera, D. N., Coarfa, C., Kadia, T. M., Khoury, J. D., et al. (2019) · Blood · doi:10.1182/blood.2018893982 · Cited by 98
Defining the oncogenic function of the TEL/AML1 (ETV6/RUNX1) fusion protein in a mouse model
Fischer, M., Schwieger, M., Horn, S., Niebuhr, B., Ford, A. M., Roscher, S., Bergholz, U., Greaves, M. F., Löhler, J., & Stocking, C. (2005) · Oncogene · doi:10.1038/sj.onc.1208931 · Cited by 99
Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development
Rothenberg, E. V., Hosokawa, H., & Ungerbäck, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00228 · Cited by 99
McNeil, S. M., Zeng, C., Harrington, K. S., Hiebert, S. W., Lian, J. B., Stein, J. L., van Wijnen, A. J., & Stein, G. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.14882 · Cited by 97
Self-citationNF-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
Telfer, J. C., & Rothenberg, E. V. (2001) · Developmental Biology · doi:10.1006/dbio.2000.9991 · Cited by 89
Wang, 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 90
Core binding factor genes and human leukemia.
Hart, S., & Foroni, L. (2002) · PubMed · Cited by 88
Transcriptional Control of Natural Killer Cell Development and Function
Hesslein, D. G. T., & Lanier, L. L. (2011) · Advances in immunology · doi:10.1016/b978-0-12-387664-5.00002-9 · Cited by 85
“1 with Runx proteins for controlling a variety of important hematopoietic genes (Goetz et al., 2000; Gu et al., 2000; Petrovick et al., 1998; Wheeler et al., 2000).”
BackgroundDifferentiation-dependent interactions between RUNX-1 and FLI-1 during megakaryocyte development.
Huang, H., Yu, M., Akie, T. E., Moran, T. B., Woo, A. J., Tu, N., Waldon, Z., Lin, Y. Y., Steen, H., & Cantor, A. B. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00090-09 · Cited by 87
“1, have been previously described (13, 15, 22, 29, 42).”
Telfer, J. C., Hedblom, E., Anderson, M. K., Laurent, M. N., & Rothenberg, E. V. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.7.4359 · Cited by 84
At the crossroads: diverse roles of early thymocyte transcriptional regulators
Anderson, M. K. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00352.x · Cited by 83
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 82
Self-citationBakshi, R., Hassan, M. Q., Pratap, J., Lian, J. B., Montecino, M. A., van Wijnen, A. J., Stein, J. L., Imbalzano, A. N., & Stein, G. S. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22240 · Cited by 84
“A large number of co-regulatory proteins associate physically with both the N-terminal DNA binding and Cterminal transcriptional regulatory domains of RUNX1 [Wotton et al., 1994; Giese et al., 1995; Hiebert et al., 1996; Rhoades et al., 1996; Petrovick et al., 1998; Rubnitz and Look, 1998; Osato et al., 1999].”
BackgroundBiggs, J. R., Peterson, L. F., Zhang, Y., Kraft, A. S., & Zhang, D. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00597-06 · Cited by 83
“The AML1 protein is composed of a DNA binding runt homology domain located in the amino terminus followed by a transcriptional activation domain and a negative regulatory C-terminal domain (15, 20, 29).”
BackgroundSelf-citationMechanisms of transcriptional regulation by Runt domain proteins
Wheeler, J. C., Shigesada, K., Gergen, J. P., & Ito, Y. (2000) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.2000.0184 · Cited by 81
Suzuki, M., Yamada, T., Kihara-Negishi, F., Sakurai, T., & Oikawa, T. (2003) · Oncogene · doi:10.1038/sj.onc.1207182 · Cited by 87
Pan, Z., Hetherington, C. J., & Zhang, D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.33.23242 · Cited by 81
Self-citationGupta, 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
“1 by forming a ternary complex on DNA [32] (Fig.”
BackgroundInfluentialThe 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 69
RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity
Chopin, M., Preston, S., Lun, A. T. L., Tellier, J., Smyth, G. K., Pellegrini, M., Belz, G. T., Corcoran, L. M., Visvader, J. E., Wu, L., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.03.066 · Cited by 73
Asou, N. (2003) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(02)00003-3 · Cited by 75
“The Runt domain of the AML1 physically interacts with C/EBPa and synergistically transactivates myeloid promoters [21,91,145].”
BackgroundWalton, 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
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 75
“Top left, HA-EVI1, HA-EVI1(1-283), and HA-EVI1(159-283) interact with PU.”
BackgroundMethodInfluentialIdentification of RUNX1/AML1 as a classical tumor suppressor gene
Silva, F. P. G., Morolli, B., Storlazzi, C. T., Anelli, L., Wessels, H. M. C., Bezrookove, V., Kluin‐Nelemans, H. C., & Giphart-Gassler, M. (2003) · Oncogene · doi:10.1038/sj.onc.1206141 · Cited by 68
“…view are reports of the interactions between RUNX1 and other transcription factors, such as Ets or C/EBPa (Giese et al., 1995; Zhang et al., 1996; Petrovick et al., 1998; Westendorf et al., 1998; Mao et al., 1999), and between RUNX1 and coactivator proteins such as p300/CREB-binding protein and…”
BackgroundPEBP2-β/CBF-β–dependent phosphorylation of RUNX1 and p300 by HIPK2: implications for leukemogenesis
Wee, H., Voon, D. C., Bae, S., & Ito, Y. (2008) · Blood · doi:10.1182/blood-2008-01-134122 · Cited by 70
Normal and transforming functions of RUNX1: A perspective
Mikhail, F. M., Sinha, K. K., Saunthararajah, Y., & Nucifora, G. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20538 · Cited by 68
“3) (Hernandez-Munain and Krangel, 1994; Zhang et al., 1996; Petrovick et al., 1998).”
c-Jun Homodimers Can Function as a Context-Specific Coactivator
Grondin, B., Lefrançois, M., Tremblay, M. R., Saint-Denis, M., Haman, A., Waga, K., Bédard, A., Tenen, D. G., & Hoang, T. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00936-06 · Cited by 62
“1 or C/EBP is enhanced through association with multiple protein partners (26, 53, 60, 61).”
BackgroundSelf-citationRUNX1 regulates corepressor interactions of PU.1
Hu, Z., Gu, X., Baraoidan, K., Ibanez, V., Sharma, A., Kadkol, S., Munker, R., Ackerman, S., Nucifora, G., & Saunthararajah, Y. (2011) · Blood · doi:10.1182/blood-2010-10-312512 · Cited by 63
“The chromosomal translocation t(8;21) is a recurrent abnor-”
BackgroundOh, I., Lau, A., & Eaves, C. J. (2000) · Blood · doi:10.1182/blood.v96.13.4160 · Cited by 63
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 63
RUNX proteins desensitize multiple myeloma to lenalidomide via protecting IKZFs from degradation
Zhou, N., Gutiérrez-Uzquiza, Á., Zheng, X. Y., Chang, R., Vogl, D. T., Garfall, A. L., Bernabei, L. L., Saraf, A., Florens, L. A., Washburn, M. P., et al. (2019) · Leukemia · doi:10.1038/s41375-019-0403-2 · Cited by 63
“At the C-terminus, RUNX1 possesses an activation domain (AD) that interacts with transcriptional co-activators, such as p300/CBP [28] and an inhibitory domain (ID) that counteracts the AD [29].”
BackgroundLibermann, T. A., Pan, Z., Akbarali, Y., Hetherington, C. J., Boltax, J., Yergeau, D. A., & Zhang, D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.35.24671 · Cited by 59
Self-citationLian, J. B., Stein, J. L., Stein, G. S., van Wijnen, A. J., Montecino, M. A., Javed, A., Gutierrez, S. E., Shen, J., Zaidi, S. K., & Drissi, H. (2003) · Connective Tissue Research · doi:10.1080/03008200390152232 · Cited by 67
Kautz, B., Kakar, R., David, E., & Eklund, E. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103381200 · Cited by 61
Bakshi, R., Zaidi, S. K., Pande, S., Hassan, M. Q., Young, D. W., Montecino, M. A., Lian, J. B., van Wijnen, A. J., Stein, J. L., & Stein, G. S. (2008) · Journal of Cell Science · doi:10.1242/jcs.033431 · Cited by 58
“…addition, a large number of co-factors interact with gene regulatory domains of RUNX1/AML1, including the C-terminus that is removed in AML1-ETO (Wotton et al., 1994; Giese et al., 1995; Hiebert et al., 1996; Rhoades et al., 1996; Petrovick et al., 1998; Rubnitz and Look, 1998; Osato et al., 1999).”
BackgroundSuraweera, N., Meijne, E., Moody, J., Carvajal-Carmona, L. G., Yoshida, K., Pollard, P., Fitzgibbon, J., Riches, A., van Laar, T., Huiskamp, R., et al. (2005) · Oncogene · doi:10.1038/sj.onc.1208422 · Cited by 60
Epigenetic consequences of AML1–ETO action at the human c‐FMS locus
Follows, G., Tagoh, H., Lefevre, P., Hodge, D., Morgan, G. J., & Bonifer, C. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg250 · Cited by 60
Melnick, A. M., Carlile, G. W., McConnell, M. J., Polinger, A., Hiebert, S. W., & Licht, J. D. (2000) · Blood · doi:10.1182/blood.v96.12.3939 · Cited by 66
Self-citationEklund, E. A., Goldenberg, I., Lu, Y., Andrejic, J., & Kakar, R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203917200 · Cited by 55
Himes, S. R., Cronau, S. L., Mulford, C., & Hume, D. A. (2005) · Oncogene · doi:10.1038/sj.onc.1208657 · Cited by 53
Runx Transcription Factors in T Cells—What Is Beyond Thymic Development?
Korinfskaya, S., Parameswaran, S., Weirauch, M. T., & Barski, A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.701924 · Cited by 47
Vegesna, V., Takeuchi, S., Hofmann, W.-K., Ikezoe, T., Tavor, S., Krug, U., Fermin, A. C., Heaney, A., Miller, C. W., & Koeffler, H. P. (2002) · Leukemia Research · doi:10.1016/s0145-2126(01)00150-3 · Cited by 54
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
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
Puig-Kröger, A., Sánchez-Elsner, T., Ruiz, N., Andreu, E. J., Prosper, F., Jensen, U. B., Gil, J., Erickson, P., Drabkin, H., Groner, Y., et al. (2003) · Blood · doi:10.1182/blood-2003-02-0618 · Cited by 51
Peterson, L. F., Boyapati, A., Ranganathan, V., Iwama, A., Tenen, D. G., Tsai, S., & Zhang, D. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.23.10205-10219.2005 · Cited by 51
Self-citationMatsumura, 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
Runx1/AML1 in leukemia: disrupted association with diverse protein partners
Perry, C., Eldor, A., & Soreq, H. (2002) · Leukemia Research · doi:10.1016/s0145-2126(01)00128-x · Cited by 51
“[16] Petrovick MS, Hiebert SW, Friedman AD, Hetherington CJ, Tenen DG, Zhang DE.”
BackgroundRUNX transcription factors at the interface of stem cells and cancer
Deltcheva, E. M., & Nimmo, R. A. (2017) · Biochemical Journal · doi:10.1042/bcj20160632 · Cited by 48
Metadata
- Authors
- Petrovick, M. S., Hiebert, S. W., Friedman, A. D., Hetherington, C. J., Tenen, D. G., & Zhang, D.-E.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Vanderbilt University (US)
- Johns Hopkins University (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1998-07
- Volume
- 18
- Issue
- 7
- Pages
- 3915-3925
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC108976
- OpenAlex
- W2138483214
- Cited by
- 218
- References
- 90
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 4 · 2012: 5
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA/AI59589, P01CA072009, R01CA041456)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- RUNX1, PU.1, C/EBPα, transcriptional synergy, cooperative DNA binding, transcription factor interaction, transactivation domain, hematopoiesis, transcriptional regulation
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Binding Sites, Cell Line, Chlorocebus aethiops, DNA, DNA-Binding Proteins, HeLa Cells, Humans, Nuclear Proteins, Phosphorylation, Promoter Regions, Genetic, Proto-Oncogene Proteins, Transcription Factors, Transcriptional Activation, Trans-Activators, Receptor, Macrophage Colony-Stimulating Factor, Mutagenesis, COS Cells, CCAAT-Enhancer-Binding Proteins, Core Binding Factor Alpha 2 Subunit
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.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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