E2F1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000077 DNA damage checkpoint signaling	IMP PMID:12717439 Chk2 activates E2F-1 in response to DNA damage.	KEEP AS NON CORE	Summary: Stevens et al. 2003 (abstract-only cache) show that CHK2 phosphorylates a consensus site in E2F1 (Ser364) after etoposide, stabilizing the protein and activating its transcription and apoptotic output; dominant-negative CHK2 blocks E2F1 induction and E2F1-dependent apoptosis. E2F1 is therefore a downstream effector of the ATM-CHK2 checkpoint kinase cascade, executing the transcriptional/apoptotic arm of the damage response, rather than a component of the checkpoint signal transduction itself. Reason: The paper establishes E2F1 as a CHK2 substrate whose stabilization couples DNA damage to transcriptional activation of pro-apoptotic genes; the authors only 'suggest a role for E2F-1 in checkpoint control'. E2F1 does not generate or transduce the checkpoint signal (ATM/ATR-CHK2 do) - it is the transcriptional output. GO:0008630 (intrinsic apoptotic signaling in response to DNA damage, same paper) and the damage-responsive transactivation captured in core_functions are the better representation; this row is kept as a non-core, DNA-damage-context annotation rather than removed, since the IMP evidence (S364A mutant, dn-CHK2) is sound. Supporting Evidence: PMID:12717439 A Chk2 consensus phosphorylation site in E2F-1 is phosphorylated in response to DNA damage, resulting in protein stabilization, increased half-life, transcriptional activation and localization of phosphorylated E2F-1 to discrete nuclear structures. PMID:12717439 These results suggest a role for E2F-1 in checkpoint control and provide a plausible explanation for the tumour suppressor activity of E2F-1.
GO:0000122 negative regulation of transcription by RNA polymerase II	IMP PMID:20224733 E2F-1 has dual roles depending on the cell cycle.	ACCEPT	Summary: Sahin & Sladek 2010 (full text) compare wild-type E2F1 with the pRB-binding-defective E2F1-Y411C mutant in murine fibroblasts: in asynchronously cycling cells wild-type E2F1, as part of the E2F1/pRB complex, represses DHFR, b-myb, TK and cdc2, whereas in cells re-entering the cycle it activates the same genes. The repression is pRB-dependent (the 411 mutant cannot repress). Reason: E2F1 does part of the work of this process: it supplies the sequence-specific DNA binding that positions the RB1 corepressor and its associated histone deacetylase activity on E2F target promoters, and the repression is lost when the E2F1-RB1 interface is disrupted (the Y411C/411 mutant cannot repress). This is a scaffold-type contribution rather than intrinsic repressor activity, and it is one half of the G1/S switch that defines E2F1 biology - the same assembly captured by GO:0035189 (Rb-E2F complex) and by core_functions[1]. Accepted rather than demoted, because grading it non-core while treating the Rb-E2F corepressor platform as a core function would be internally inconsistent. Supporting Evidence: PMID:20224733 E2F-1 acts as part of the repression complex with pRB in the expression of DHFR, b-myb, TK and cdc2 in asynchronously growing cells; on the other hand, E2F-1 acts as an activator in the expression of the same genes in cells that are re-entering the cycle.
GO:0000228 nuclear chromosome	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl Compara transfer from rat E2f1 of nuclear chromosome localization. E2F1 is a chromatin-bound nuclear TF occupying E2F-site promoters and, after DNA damage, sites of UV lesions and double-strand breaks. Reason: Consistent with the direct chromatin (GO:0000785 IDA) and nucleus evidence; the chromosome term is a coarser but correct parent.
GO:0000785 chromatin	IDA PMID:21454377 MiR-15 and miR-16 are direct transcriptional targets of E2F1...	ACCEPT	Summary: ChIP shows endogenous E2F1 bound to the miR-15/16 cluster promoters (Ofir et al. 2011). Reason: Promoter ChIP is direct evidence of chromatin occupancy; E2F1 acts on chromatin. Core location. Supporting Evidence: PMID:21454377 Moreover, activation of endogenous E2Fs upregulates expression of these miRs and endogenous E2F1 binds their respective promoters.
GO:0000785 chromatin	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl Compara transfer of chromatin localization from mouse E2f1. Reason: Canonical location, directly supported by ChIP on human E2F1.
GO:0000785 chromatin	ISA GO_REF:0000113	ACCEPT	Summary: TFClass-derived chromatin localization for the E2F class. Reason: Canonical location for a sequence-specific TF, experimentally supported.
GO:0000976 transcription cis-regulatory region binding	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl Compara transfer from mouse E2f1 of transcription cis-regulatory region binding. Reason: Correct, broader parent of the IBA-supported GO:0000978; acceptable IEA generality.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: PAINT-inferred Pol II cis-regulatory region sequence-specific DNA binding for the E2F node (mouse E2f1/E2f3 and human E2F5/E2F7 experimental descendants). E2F1-DP heterodimers bind the TTTC[CG]CGC E2F consensus in Pol II promoters via the winged-helix domain (residues 110-194). Reason: Defining DNA-binding activity of the family and of E2F1; consistent with SELEX (PMID:23332764, PMID:28473536) and promoter ChIP data on E2F1 itself. Core function. Supporting Evidence: file:human/E2F1/E2F1-uniprot.txt Transcription activator that binds DNA cooperatively with DP
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO mapping from the E2F family entry IPR015633. Reason: Correct family-level mapping, consistent with IBA and experimental evidence.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	ACCEPT	Summary: PAINT-inferred DNA-binding transcription factor activity, RNA polymerase II-specific, for the E2F family node (fly E2f1/E2f2, mouse E2f1/E2f3, human E2F1-6 among the experimental descendants, including E2F1 itself). E2F1-DP heterodimers bind TTTC[CG]CGC E2F sites in Pol II promoters and activate transcription. Reason: The defining molecular function of E2F1; robust phylogenetic placement with experimental grounding on the target itself. Core function (core_functions[0]). Supporting Evidence: file:human/E2F1/E2F1-uniprot.txt Transcription activator that binds DNA cooperatively with DP file:human/E2F1/E2F1-deep-research-falcon.md Its primary molecular function is to act in the nucleus as a sequence-specific, DP-dependent transcriptional activator.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IMP PMID:20040599 Regulation of E2F1-induced apoptosis by the nucleolar protei...	ACCEPT	Summary: RRP1B promoter analysis demonstrates selective E2F1-responsive transactivation (Paik et al. 2010). Reason: Direct promoter-level evidence for Pol II-specific transcription factor activity; canonical function. Supporting Evidence: PMID:20040599 We now identify a nucleolar protein, RRP1B, as an E2F1-specific transcriptional target. We characterize the RRP1B promoter and demonstrate its selective response to E2F1.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	ISA GO_REF:0000113	ACCEPT	Summary: TFClass-based annotation (class 3.3.2, E2F-related winged-helix factors) of sequence-specific Pol II DNA-binding transcription factor activity. Reason: E2F1 is the founding member of the E2F winged-helix class; correct.
GO:0000987 cis-regulatory region sequence-specific DNA binding	IDA PMID:15735762 Induction of human metallothionein 1G promoter by VEGF and h...	ACCEPT	Summary: Joshi et al. 2005: ChIP shows E2F1-3 bind the endogenous human MT1G promoter E2F sites upon VEGF stimulation of aortic endothelial cells, with concomitant loss of pocket-protein occupancy; E2F1 induces the hMT1G promoter in transfection. Reason: Direct cis-regulatory region binding at E2F sites. The more specific Pol II child GO:0000978 is also annotated; this parent is not wrong and is retained. Supporting Evidence: PMID:15735762 VEGF stimulation led to an increased binding of E2Fs 1-3 to the endogenous hMT1G promoter; at the same time, the binding of Rb, p107 and p130 to the promoter was abolished. PMID:15735762 hMT1G promoter could be induced by E2F1 in transient transfections; further, deletion analysis suggested that the region spanning the E2F-binding sites was necessary for VEGF-mediated induction.
GO:0001216 DNA-binding transcription activator activity	IDA PMID:28992046 Phosphorylated E2F1 is stabilized by nuclear USP11 to drive ...	MODIFY	Summary: USP11-stabilized E2F1 drives PEG10 transcription (Wang et al. 2018). Reason: Correct but E2F1 acts exclusively on RNA polymerase II promoters; the Pol II-specific child GO:0001228 (already annotated) is the appropriate level. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:28992046 Downregulation of USP11 increases E2F1 ubiquitination and reduces E2F1 stability and protein levels, thereby decreasing Peg10 mRNA levels.
GO:0001216 DNA-binding transcription activator activity	IEA GO_REF:0000107	MODIFY	Summary: Ensembl Compara transfer from mouse E2f1 of DNA-binding transcription activator activity. Reason: Correct in essence; the Pol II-specific child GO:0001228 is the informative term and is experimentally annotated. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific	IDA PMID:17062573 Human TFDP3, a novel DP protein, inhibits DNA binding and tr...	ACCEPT	Summary: Qiao et al. 2007: E2F1 heterodimerizes with TFDP1/2 to give high-affinity E2F-site binding and transcriptional activation, whereas TFDP3 heterodimers fail to bind the E2F consensus and inhibit E2F-mediated activation. E2F1 transactivation was directly assayed. Reason: The most specific MF term for E2F1's defining activity - a Pol II-specific DNA-binding transcription activator (as the E2F1-DP heterodimer). Core function. Supporting Evidence: PMID:17062573 The two known DP proteins, TFDP1 and -2, bind E2Fs to form heterodimers essential for high affinity DNA binding and efficient transcriptional activation/repression. PMID:17062573 Although TFDP3 retained the capacity to bind to E2F proteins, the resulting heterodimers failed to interact with the E2F consensus sequence.
GO:0003677 DNA binding	IDA PMID:15073182 Heregulin regulates the ability of the ErbB3-binding protein...	MODIFY	Summary: Zhang & Hamburger 2004: Ebp1 associates with E2F1 consensus oligonucleotides together with E2F1, pRB and HDAC2 (EMSA/ChIP on the E2F1 promoter). E2F1 DNA binding is incidental to the paper's focus on Ebp1. Reason: Bare 'DNA binding' is uninformative for a sequence-specific TF; the assay shows E2F-site binding, i.e. GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding), already annotated by IBA. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:15073182 Ebp1 bound E2F consensus oligonucleotides in association with E2F1, retinoblastoma protein, and HDAC2.
GO:0003677 DNA binding	IDA PMID:15731768 ASPP1 and ASPP2 are new transcriptional targets of E2F.	MODIFY	Summary: E2F1 binds the ASPP1/ASPP2 promoters in vivo (ChIP). Reason: Promoter ChIP demonstrates cis-regulatory region binding; the specific term GO:0000978 is more informative than generic DNA binding. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:15731768 We show here that E2F-1 binds in vivo the promoters of ASPP1 and ASPP2 genes, two activators of p53-mediated apoptosis, E2F-1, E2F-2 and E2F-3 all activate the isolated ASPP1 and ASPP2 promoters.
GO:0003677 DNA binding	IMP PMID:11418595 E2F transcriptional activation requires TRRAP and GCN5 cofac...	MODIFY	Summary: Lang et al. 2001 map transactivation-domain mutants affecting coactivator recruitment; DNA binding itself is a background property of the E2F-DP heterodimer in this paper. Reason: Generic DNA binding is uninformative; replace with the sequence-specific Pol II cis-regulatory term that describes E2F1's actual DNA-binding activity. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:11418595 We conclude that E2F stimulates transcription by recruiting acetyltransferase activity and the essential cofactors GCN5 and TRRAP.
GO:0003700 DNA-binding transcription factor activity	IDA PMID:15731768 ASPP1 and ASPP2 are new transcriptional targets of E2F.	MODIFY	Summary: Fogal et al. 2005: E2F1 binds the ASPP1 and ASPP2 promoters in vivo and activates them. Reason: Generic parent of GO:0000981/GO:0001228; E2F1's activity is Pol II-specific and the ASPP promoters are Pol II genes. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:15731768 We show here that E2F-1 binds in vivo the promoters of ASPP1 and ASPP2 genes, two activators of p53-mediated apoptosis, E2F-1, E2F-2 and E2F-3 all activate the isolated ASPP1 and ASPP2 promoters.
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000107	MODIFY	Summary: Ensembl Compara transfer from mouse E2f1 of generic DNA-binding transcription factor activity. Reason: Generic parent; the Pol II-specific GO:0000981 is the informative level and is supported by IBA/ISA/IMP. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific
GO:0003700 DNA-binding transcription factor activity	TAS PMID:11418595 E2F transcriptional activation requires TRRAP and GCN5 cofac...	MODIFY	Summary: Lang et al. 2001 (TAS): E2F1's transactivation domain recruits GCN5/TRRAP to stimulate transcription. Reason: Generic parent term; Pol II-specific GO:0000981 is the informative level. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:11418595 We conclude that E2F stimulates transcription by recruiting acetyltransferase activity and the essential cofactors GCN5 and TRRAP.
GO:0005515 protein binding	IPI PMID:11418595 E2F transcriptional activation requires TRRAP and GCN5 cofac...	MODIFY	Summary: Lang et al. 2001: the E2F1 transactivation domain binds the cofactor TRRAP (with GCN5) in vivo, and TRRAP/GCN5 co-expression stimulates E2F transactivation. Reason: TRRAP is a transcription coactivator (scaffold of SAGA/TIP60 HAT complexes) recruited by the E2F1 activation domain; GO:0001223 is the informative term. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:11418595 Here we map the E2F-4 transactivation domain and show that E2F-1 and E2F-4 transactivation domains bind the acetyltransferase GCN5 and cofactor TRRAP in vivo. PMID:11418595 We conclude that E2F stimulates transcription by recruiting acetyltransferase activity and the essential cofactors GCN5 and TRRAP.
GO:0005515 protein binding	IPI PMID:11486038 Mre11 complex and DNA replication: linkage to E2F and sites ...	REMOVE	Summary: Maser et al. 2001: E2F1 was identified in a two-hybrid screen with the Nbs1 N terminus; the Mre11 complex co-immunoprecipitates with E2F1 and E2F1 targets it to E2F sites near replication origins. Reason: Generic protein binding is uninformative; the interaction is real and interesting (E2F1 tethering the MRN complex to origin-proximal E2F sites) but no informative GO MF term describes it, and its functional consequence remains untested. Supporting Evidence: PMID:11486038 We identified the E2F1 transcription factor in a screen for proteins that interacted with the Nbs1 N-terminal region and established evidence that this interaction occurs on chromatin near a defined DNA replication origin.
GO:0005515 protein binding	IPI PMID:12502741 Structural basis for the recognition of the E2F transactivat...	MODIFY	Summary: Lee et al. 2002: crystal structure of the Rb pocket bound to an E2F transactivation-domain peptide, explaining how RB1 masks the E2F activation surface. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:12502741 Repression of E2F transcription activity by the retinoblastoma (Rb) tumor suppressor through its interaction with the transactivation domain of the E2F transcription factor is one of the central features of G1/S arrest in the mammalian cell cycle.
GO:0005515 protein binding	IPI PMID:12598654 Crystal structure of the retinoblastoma tumor suppressor pro...	REMOVE	Summary: The same structural study also addresses HPV E7 displacement of E2F from pRB. E7 is a viral oncoprotein, not a human gene product. Reason: Generic protein binding to a viral protein is uninformative about E2F1's own function; the interaction (E7 binding/displacing E2F from pRB) is a host-virus relationship better recorded in UniProt than as an E2F1 MF annotation. Supporting Evidence: PMID:16249186 Mutation of residues within these patches reveals that one patch is required for pRb binding, whereas the other is required for E2F binding.
GO:0005515 protein binding	IPI PMID:12598654 Crystal structure of the retinoblastoma tumor suppressor pro...	MODIFY	Summary: Xiao et al. 2003: crystal structure of the pRB pocket bound to E2F1 residues 409-426 (the core RB-binding region of E2F1). Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:12598654 The fragment of E2F used in our structural studies, residues 409–426 of E2F-1, represents the core of the pRb-binding region of the transcription factor.
GO:0005515 protein binding	IPI PMID:14627987 PARP-1 binds E2F-1 independently of its DNA binding and cata...	MODIFY	Summary: Simbulan-Rosenthal et al. 2003: PARP-1 binds E2F1 independently of its DNA-binding and catalytic domains and acts as a coactivator during S-phase re-entry. Reason: PARP1 acts here as a transcription coactivator of E2F1; GO:0001223 is the informative term. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:14627987 Protein-binding reactions and coimmunoprecipitation experiments with purified PARP-1 and E2F-1, however, revealed that PARP-1 binds to E2F-1 in vitro.
GO:0005515 protein binding	IPI PMID:16061792 Association of the human papillomavirus type 16 E7 oncoprote...	REMOVE	Summary: Huh et al. 2005 (HPV16 E7-p600 TAP/MS); E2F1 is peripheral to the paper's findings. Reason: Uninformative generic binding to a viral protein; not an E2F1 function.
GO:0005515 protein binding	IPI PMID:16249186 Structure of the human Papillomavirus E7 oncoprotein and its...	MODIFY	Summary: Liu et al. 2006: HPV E7 CR3 structure and mutational analysis of pRb and E2F binding; RB1 is the E2F1 partner recorded here. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:16249186 Mutation of residues within these patches reveals that one patch is required for pRb binding, whereas the other is required for E2F binding.
GO:0005515 protein binding	IPI PMID:16360038 Structure of the Rb C-terminal domain bound to E2F1-DP1: a m...	MODIFY	Summary: Rubin et al. 2005 RbC-E2F1-DP1 crystal structure. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:16360038 The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC.
GO:0005515 protein binding	IPI PMID:16360038 Structure of the Rb C-terminal domain bound to E2F1-DP1: a m...	MODIFY	Summary: Rubin et al. 2005: E2F1 and DP1 form an intertwined coiled-coil/marked-box heterodimer. Reason: TFDP1 is E2F1's obligate heterodimerization partner; 'protein heterodimerization activity' (GO:0046982) captures the structural finding, and GO:0140297 (already annotated from this paper) captures that DP1 is a DNA-binding TF. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:16360038 The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC.
GO:0005515 protein binding	IPI PMID:16374512 DNA-damage-responsive acetylation of pRb regulates binding t...	MODIFY	Summary: Markham et al. 2006: DNA-damage-responsive acetylation of pRb K873/874 regulates binding of the pRb C-terminal E2F1-specific domain to E2F1. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:16374512 Here, we report that the acetylation of pRb K873/874 occurs in response to DNA damage and that acetylation regulates the interaction between the C-terminal E2F-1-specific domain of pRb and E2F-1.
GO:0005515 protein binding	IPI PMID:16892051 Interactions between E2F1 and SirT1 regulate apoptotic respo...	MODIFY	Summary: Same study; mouse Sirt1 also binds E2F1. Reason: Mouse Sirt1 ortholog of the deacetylase partner; GO:0042826 is the informative term. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:16892051 Furthermore, SirT1 binds to E2F1 and inhibits E2F1 activities, forming a negative feedback loop.
GO:0005515 protein binding	IPI PMID:16892051 Interactions between E2F1 and SirT1 regulate apoptotic respo...	MODIFY	Summary: Wang et al. 2006: SIRT1 binds E2F1 and inhibits its transcriptional and apoptotic activities; E2F1 in turn induces SIRT1 transcription (negative feedback). Reason: SIRT1 is an NAD-dependent (histone) deacetylase that deacetylates and inhibits E2F1; GO:0042826 is the informative term. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:16892051 Furthermore, SirT1 binds to E2F1 and inhibits E2F1 activities, forming a negative feedback loop.
GO:0005515 protein binding	IPI PMID:17006541 Regulation of TopBP1 oligomerization by Akt/PKB for cell sur...	REMOVE	Summary: Liu et al. 2006: TopBP1 (BRCT domain protein) binds E2F1 specifically and represses its pro-apoptotic activity; Akt-induced TopBP1 oligomerization is required for the interaction. Reason: Generic term is uninformative; TOPBP1 is a repressor of E2F1 apoptosis and a recruiter of E2F1 to DNA lesions, but no GO MF term describes this non-enzymatic regulatory interaction. Removal does not question the interaction. Supporting Evidence: PMID:17006541 This control requires TopBP1, a BRCT (BRCA1 carboxyl-terminal) domain-containing protein, which interacts with E2F1 but not other E2Fs and represses its proapoptotic activity.
GO:0005515 protein binding	IPI PMID:17062573 Human TFDP3, a novel DP protein, inhibits DNA binding and tr...	MODIFY	Summary: Qiao et al. 2007: TFDP3 binds E2F1 but the heterodimer cannot bind the E2F consensus and inhibits E2F activation. Reason: TFDP3 heterodimerizes with E2F1 (a dominant-negative DP); GO:0046982 is the informative term. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:17062573 Although TFDP3 retained the capacity to bind to E2F proteins, the resulting heterodimers failed to interact with the E2F consensus sequence.
GO:0005515 protein binding	IPI PMID:17380128 Phosphorylation of pRB at Ser612 by Chk1/2 leads to a comple...	MODIFY	Summary: Inoue et al. 2007: CHK1/2 phosphorylation of pRB Ser612 after DNA damage enhances pRB-E2F1 complex formation. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:17380128 Phosphorylation of pRB at Ser612 enhanced the formation of a complex between pRB and E2F-1.
GO:0005515 protein binding	IPI PMID:17517653 A genome-wide RNA interference screen identifies putative ch...	MODIFY	Summary: Lu et al. 2007: L3MBTL-family proteins are recruited to E2F promoters through E2F association (fly screen, human L3MBTL3 recorded). Reason: L3MBTL3 is a Polycomb-like transcription corepressor recruited via E2F; GO:0001222 is the informative term. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:17517653 These factors are recruited to E2F-responsive promoters through physical association with E2F and are required for repression of endogenous E2F target genes.
GO:0005515 protein binding	IPI PMID:17690688 The candidate tumor suppressor BTG3 is a transcriptional tar...	REMOVE	Summary: Ou et al. 2007: the p53 target BTG3 binds and inhibits E2F1, disrupting its DNA binding. Reason: Generic term is uninformative and no GO MF term captures 'being inhibited by BTG3'; the biology is a regulatory input on E2F1. Interaction not disputed. Supporting Evidence: PMID:17690688 In vitro, BTG3 binds to and inhibits E2F1 through an N-terminal domain including the conserved box A.
GO:0005515 protein binding	IPI PMID:17704056 Regulation of E2F1 function by the nuclear corepressor KAP1.	MODIFY	Summary: Wang et al. 2007: the nuclear corepressor KAP1/TRIM28 binds E2F1 pRb-independently, promotes E2F1-HDAC1 complex formation, blocks E2F1 acetylation and represses E2F1 transcription and apoptosis. Reason: TRIM28 is a transcription corepressor; GO:0001222 is the informative term. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:17704056 Here we report that KAP1 binds the E2F1 transcription factor in a retinoblastoma protein (pRb)-independent fashion and inhibits E2F1 activity.
GO:0005515 protein binding	IPI PMID:17704056 Regulation of E2F1 function by the nuclear corepressor KAP1.	MODIFY	Summary: Same study: KAP1 stimulates formation of an E2F1-HDAC1 complex that deacetylates E2F1. Reason: HDAC1 is a histone deacetylase recruited to E2F1 (here via KAP1, classically via RB1); GO:0042826 is the informative term. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:17704056 KAP1 stimulates formation of E2F1-HDAC1 complex and inhibits E2F1 acetylation.
GO:0005515 protein binding	IPI PMID:18660514 Multimolecular complex of Par-4 and E2F1 binding to Smac pro...	REMOVE	Summary: Lu et al. 2008: Par-4 and E2F1 form a complex on the Smac promoter; E2F1 provides the direct DNA contact. Reason: Generic term is uninformative; the relevant E2F1 activity (promoter binding) is captured by the DNA-binding rows. Interaction not disputed. Supporting Evidence: PMID:18660514 Moreover, in the complex, E2F1, not Par-4, was found to be directly bound to the Smac promoter, suggesting that Par-4 exerted indirectly its transcriptional control on the Smac gene though interacting with E2F1.
GO:0005515 protein binding	IPI PMID:18660752 MCPH1/BRIT1 cooperates with E2F1 in the activation of checkp...	MODIFY	Summary: Yang et al. 2008: MCPH1/BRIT1 interacts with E2F1 on CHK1, BRCA1 and p73 promoters and is required for E2F1-dependent checkpoint/repair/apoptosis gene induction. Reason: MCPH1 functions here as a promoter-bound coactivator of E2F1 target genes; GO:0001223 is the informative term. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:18660752 MCPH1 interacts with E2F1 on the p73 promoter, and regulates p73 induction and E2F1-induced apoptosis as a result of DNA damage.
GO:0005515 protein binding	IPI PMID:18794899 E2F1 represses beta-catenin transcription and is antagonized...	MODIFY	Summary: Morris et al. 2008: E2F1 represses beta-catenin/TCF transcription and is antagonized by CDK8 (Mediator kinase), which binds E2F1. Reason: CDK8 is a protein kinase that binds and inhibits E2F1; GO:0019901 (protein kinase binding), already annotated by IEA, is the informative term. Proposed replacements: protein kinase binding Supporting Evidence: PMID:18794899 Here we show that E2F1 is a potent and specific inhibitor of beta-catenin/T-cell factor (TCF)-dependent transcription, and that this function contributes to E2F1-induced apoptosis.
GO:0005515 protein binding	IPI PMID:19188449 hSirT1-dependent regulation of the PCAF-E2F1-p73 apoptotic p...	MODIFY	Summary: Pediconi et al. 2009: hSirT1, PCAF and E2F1 are co-recruited to the P1p73 promoter; SirT1 represses E2F1-dependent TP73 activation. Reason: Deacetylase partner on the p73 promoter; GO:0042826 is the informative term. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:19188449 The release of PCAF from hSirT1 repression favors the assembly of transcriptionally active PCAF/E2F1 complexes onto the P1p73 promoter and p53-independent apoptosis.
GO:0005515 protein binding	IPI PMID:19249677 Proapoptotic function of the retinoblastoma tumor suppressor...	MODIFY	Summary: Ianari et al. 2009: DNA damage and E1A oncogenic stress promote a pRB-E2F1 complex on transcriptionally active pro-apoptotic promoters. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:19249677 Here we show that DNA damage and E1A-induced oncogenic stress promote formation of a pRB-E2F1 complex even in proliferating cells.
GO:0005515 protein binding	IPI PMID:20040599 Regulation of E2F1-induced apoptosis by the nucleolar protei...	MODIFY	Summary: Paik et al. 2010: RRP1B, an E2F1 target, forms complexes with E2F1 on selective pro-apoptotic promoters and is required for their expression. Reason: RRP1B acts as a promoter-specific coactivator of E2F1; GO:0001223 is the informative term. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:20040599 This activity is mediated in part by complex formation between RRP1B and E2F1 on selective E2F1 target gene promoters.
GO:0005515 protein binding	IPI PMID:20133863 Inhibition of poly(ADP-ribose) polymerase down-regulates BRC...	REMOVE	Summary: Hegan et al. 2010: PARP inhibition down-regulates BRCA1/RAD51 via E2F4/p130; E2F1-PARP1 interaction recorded. Reason: Generic and uninformative; the paper's mechanism concerns E2F4/p130 rather than E2F1.
GO:0005515 protein binding	IPI PMID:20195357 A comprehensive resource of interacting protein regions for ...	MODIFY	Summary: Miyamoto-Sato et al. 2010 high-throughput TF interacting-region resource; STAT1-E2F1 pair. Reason: STAT1 is a DNA-binding TF; GO:0140297 is the informative term (high-throughput evidence, functional consequence uncharacterized). Proposed replacements: DNA-binding transcription factor binding
GO:0005515 protein binding	IPI PMID:20195357 A comprehensive resource of interacting protein regions for ...	MODIFY	Summary: Miyamoto-Sato et al. 2010 high-throughput resource; NCOR2/SMRT-E2F1 pair. Reason: NCOR2 is a transcription corepressor; GO:0001222 is the informative term (high-throughput evidence). Proposed replacements: transcription corepressor binding
GO:0005515 protein binding	IPI PMID:20211142 An atlas of combinatorial transcriptional regulation in mous...	MODIFY	Summary: Ravasi et al. 2010 combinatorial TF-TF interaction atlas (M2H); E2F1-TFDP1 recovered. Reason: Obligate heterodimer partner; GO:0046982 is the informative term. Proposed replacements: protein heterodimerization activity
GO:0005515 protein binding	IPI PMID:20224733 E2F-1 has dual roles depending on the cell cycle.	MODIFY	Summary: Co-IP of E2F1 with mouse pRb in psi-CRE fibroblasts (Sahin & Sladek 2010). Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:20224733 E2F-1 acts as part of the repression complex with pRB in the expression of DHFR, b-myb, TK and cdc2 in asynchronously growing cells; on the other hand, E2F-1 acts as an activator in the expression of the same genes in cells that are re-entering the cycle.
GO:0005515 protein binding	IPI PMID:20622854 PHF8 mediates histone H4 lysine 20 demethylation events invo...	MODIFY	Summary: Liu et al. 2010: the H4K20me1 demethylase PHF8 controls G1-S in conjunction with E2F1, HCF-1 and SET1A at E2F1-regulated promoters. Reason: PHF8 is a chromatin coactivator recruited to E2F1 target promoters; GO:0001223 is the informative term. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:20622854 PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1-S transition in conjunction with E2F1, HCF-1 (also known as HCFC1) and SET1A (also known as SETD1A)
GO:0005515 protein binding	IPI PMID:20729920 TRIM16 acts as a tumour suppressor by inhibitory effects on ...	REMOVE	Summary: Marshall et al. 2010: TRIM16 binds nuclear E2F1 in neuroblastoma cells and reduces E2F1 levels. Reason: Generic term is uninformative; tumour-type-specific regulatory interaction without a corresponding informative MF term. Interaction not disputed. Supporting Evidence: PMID:20729920 TRIM16 bound directly to cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells.
GO:0005515 protein binding	IPI PMID:20871633 p38 phosphorylates Rb on Ser567 by a novel, cell cycle-indep...	MODIFY	Summary: Delston et al. 2011 (p38 phosphorylation of Rb Ser567); E2F1-Rb binding assayed as part of Rb functional characterisation. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding
GO:0005515 protein binding	IPI PMID:20972224 GCN5 and E2F1 stimulate nucleotide excision repair by promot...	MODIFY	Summary: Guo et al. 2011: E2F1 associates with GCN5 after UV and recruits it to sites of damage, where H3K9 acetylation requires both proteins; transcription-independent role in NER. Reason: GCN5/KAT2A is a histone acetyltransferase; GO:0035035 is the informative term. Proposed replacements: histone acetyltransferase binding Supporting Evidence: PMID:20972224 Here we demonstrate that E2F1 associates with the GCN5 histone acetyltransferase in response to UV radiation and recruits GCN5 to sites of damage.
GO:0005515 protein binding	IPI PMID:21653699 Cellular inhibitor of apoptosis protein-1 (cIAP1) can regula...	MODIFY	Summary: Cartier et al. 2011: nuclear cIAP1/BIRC2 directly binds the E2F1 DNA-binding domain and increases E2F1 transactivation of CCNE/CCNA. Reason: BIRC2 acts here as a transcription coactivator of E2F1 on cyclin promoters; GO:0001223 is the informative term. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:21653699 Here, we show that the N-terminal part of cIAP1 directly interacts with the DNA binding domain of the E2F1 transcription factor.
GO:0005515 protein binding	IPI PMID:22327218 Arginine methylation controls growth regulation by E2F-1.	REMOVE	Summary: Cho et al. 2012: PRMT5 directly methylates E2F1 arginines, controlling its stability and DNA-binding activity. Reason: Generic term is uninformative; PRMT5 is an enzyme acting on E2F1 (E2F1 is the substrate), which is not an E2F1 molecular function. Interaction not disputed. Supporting Evidence: PMID:22327218 We show here that E2F-1 is directly methylated by PRMT5 (protein arginine methyltransferase 5), and that arginine methylation is responsible for regulating its biochemical and functional properties
GO:0005515 protein binding	IPI PMID:22327218 Arginine methylation controls growth regulation by E2F-1.	MODIFY	Summary: Cho et al. 2012 (PRMT5 arginine methylation of E2F1); E2F1-DP1 heterodimer assayed. Reason: Obligate heterodimer partner; GO:0046982 is the informative term. Proposed replacements: protein heterodimerization activity
GO:0005515 protein binding	IPI PMID:22810586 Interpreting cancer genomes using systematic host network pe...	REMOVE	Summary: Rozenblatt-Rosen et al. 2012 systematic tumour-virus host network; HPV E7-E2F1 recovered. Reason: Uninformative generic binding to a viral protein from a high-throughput screen.
GO:0005515 protein binding	IPI PMID:23472054 The ING1a tumor suppressor regulates endocytosis to induce c...	MODIFY	Summary: Rajarajacholan et al. 2013 (ING1a senescence via Rb-E2F); Rb-E2F1 interaction assessed. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding
GO:0005515 protein binding	IPI PMID:23629655 Mixed lineage leukemia 5 (MLL5) protein regulates cell cycle...	MODIFY	Summary: Zhou et al. 2013: HCF-1 associates with E2F1 and bridges MLL5 to E2F1-responsive promoters for H3K4 trimethylation. Reason: HCFC1 is a transcription coactivator that couples E2F1 to the MLL5/SET1 H3K4 methyltransferase; GO:0001223 is the informative term. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:23629655 Conclusion: MLL5 stimulates H3K4 trimethylation at E2F1 responsive promoters and cause transcriptional activation of E2F1 target genes to facilitate the G 1 to S phase transition.
GO:0005515 protein binding	IPI PMID:24502362 Regulation of DNA methyltransferase 1 transcription in BRCA1...	MODIFY	Summary: Li et al. 2014: E2F1 and KAT2A/H3K9ac at the DNMT1 promoter in BRCA1-mutant breast cancer. Reason: GCN5/KAT2A is a histone acetyltransferase partner of E2F1; GO:0035035 is the informative term. Proposed replacements: histone acetyltransferase binding
GO:0005515 protein binding	IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme...	MODIFY	Summary: Marcon et al. 2014 chromatin-related protein interaction map; E2F1-TFDP1 recovered. Reason: Obligate heterodimer partner; GO:0046982 is the informative term. Proposed replacements: protein heterodimerization activity
GO:0005515 protein binding	IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex...	MODIFY	Summary: Hauri et al. 2016 Polycomb complexome AP-MS; E2F1-TFDP1 recovered. Reason: Obligate heterodimer partner; GO:0046982 is the informative term. Proposed replacements: protein heterodimerization activity
GO:0005515 protein binding	IPI PMID:29521627 A compartmentalized signaling network mediates crossover con...	MODIFY	Summary: Zhang et al. 2018 (C. elegans meiotic crossover signaling network); a mammalian Rb-E2F1 interaction appears only as a methodological control/comparator in this paper. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. The paper's subject (worm meiosis) is unrelated to E2F1 biology, but the RB1-E2F1 pair itself is beyond doubt. Proposed replacements: transcription corepressor binding
GO:0005515 protein binding	IPI PMID:29691401 Methylated DNMT1 and E2F1 are targeted for proteolysis by L3...	REMOVE	Summary: Leng et al. 2018: L3MBTL3 binds SETD7-methylated K185 of E2F1 and recruits CRL4-DCAF5 for proteolysis. Reason: Generic term is uninformative; the interaction is a degradation-targeting event (methyl-lysine reader) rather than a molecular function of E2F1. Interaction not disputed.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Haenig et al. 2020 neurodegenerative-disease interactome (Y2H); APP-E2F1 pair. Reason: High-throughput two-hybrid pair without functional follow-up; generic term uninformative.
GO:0005515 protein binding	IPI PMID:34591612 A protein interaction landscape of breast cancer.	MODIFY	Summary: Kim et al. 2021 breast cancer AP-MS interaction landscape; RB1-E2F1 recovered. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding
GO:0005515 protein binding	IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA...	MODIFY	Summary: Swaney et al. 2021 head-and-neck cancer AP-MS network; RB1-E2F1 recovered. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding
GO:0005515 protein binding	IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA...	MODIFY	Summary: Swaney et al. 2021 AP-MS network; TFDP1-E2F1 heterodimer recovered. Reason: TFDP1 is the obligate heterodimeric partner; GO:0046982 is the informative term. Proposed replacements: protein heterodimerization activity
GO:0005515 protein binding	IPI PMID:35140242 Human transcription factor protein interaction networks.	MODIFY	Summary: Goos et al. 2022 human TF interactome (AP-MS/BioID); RB1-E2F1 recovered. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding
GO:0005515 protein binding	IPI PMID:35140242 Human transcription factor protein interaction networks.	MODIFY	Summary: Goos et al. 2022 TF interactome; TFDP1-E2F1 recovered. Reason: Obligate heterodimer partner; GO:0046982 is the informative term. Proposed replacements: protein heterodimerization activity
GO:0005515 protein binding	IPI PMID:35140242 Human transcription factor protein interaction networks.	MODIFY	Summary: Goos et al. 2022 TF interactome; KAT2A (GCN5) recovered with E2F1, consistent with the targeted GCN5 recruitment studies. Reason: GCN5/KAT2A is the histone acetyltransferase E2F1 recruits to promoters and to UV lesions (PMID:11418595, PMID:20972224); 'histone acetyltransferase binding' (GO:0035035) is the informative term. Proposed replacements: histone acetyltransferase binding
GO:0005515 protein binding	IPI PMID:39938803 Structural and functional analysis of cancer-associated miss...	MODIFY	Summary: Castro et al. 2025: fluorescence-polarization binding of Rb pocket cancer variants to the E2F1 transactivation-domain peptide. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:39938803 In this FP assay, a peptide of the E2F1 transactivation domain that is N-labeled with tetramethyl rhodamine dye (TMR-E2F1TD) is measured in the presence of unl
GO:0005515 protein binding	IPI PMID:7784053 Cloning and characterization of human DP2, a novel dimerizat...	MODIFY	Summary: Zhang & Chellappan 1995: cloning of DP2 (TFDP2), which dimerizes with E2F to form a DNA-binding heterodimer. Reason: TFDP2 is an alternative obligate heterodimerization partner; GO:0046982 is the informative term. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:7784053 DP2 binds to E2F as detected by in vitro reconstitution assays and an E2F-DP2 heterodimer can bind to DNA in gel-retardation assays.
GO:0005515 protein binding	IPI PMID:8336704 A bipartite nuclear localization signal in the retinoblastom...	MODIFY	Summary: Zacksenhaus et al. 1993: RB1 NLS mutants retain in vitro binding to E2F. Reason: RB1 is the transcription corepressor that binds the E2F1 transactivation domain and marked box; 'transcription corepressor binding' (GO:0001222) is the informative MF term for this interaction, which underlies the Rb-E2F complex rows. Generic protein binding carries no functional information. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:8336704 Neither NLS(NQ) nor delta NLS was hyperphosphorylated in vivo, but both retained their abilities to interact, in vitro, with simian virus 40 large T antigen, adenovirus E1a, and the cellular transcription factor E2F.
GO:0005515 protein binding	IPI PMID:8657141 Interaction of Sp1 with the growth- and cell cycle-regulated...	MODIFY	Summary: Karlseder et al. 1996: E2F1-3 (via the N terminus) bind Sp1 in vitro and in vivo, and the two factors cooperate on the thymidine kinase promoter. Reason: SP1 is a DNA-binding transcription factor; GO:0140297 is the informative term. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:8657141 This was verified by demonstrating with the use of glutathione S-transferase fusion proteins that E2F and Sp1 bind to each other in vitro.
GO:0005515 protein binding	IPI PMID:9418871 DDB, a putative DNA repair protein, can function as a transc...	MODIFY	Summary: Hayes et al. 1998: DDB (DDB2 p48 subunit) binds the E2F1 activation domain and stimulates E2F1-activated transcription. Reason: The paper characterizes DDB as a transcriptional partner that stimulates E2F1 transactivation; GO:0001223 is the informative term. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:9418871 Here we show that DDB, a putative DNA repair protein, associates with the activation domain of E2F1.
GO:0005515 protein binding	IPI PMID:9468139 Retinoblastoma protein recruits histone deacetylase to repre...	MODIFY	Summary: Brehm et al. 1998: Rb associates with HDAC1 through its pocket and can recruit the deacetylase to E2F to repress cyclin E; the E2F1-HDAC1 association is Rb-bridged. Reason: The functional relationship (HDAC1 recruited to E2F1-bound promoters) is captured by 'histone deacetylase binding'; the generic term is uninformative. The abstract indicates the association is via Rb, which the replacement term does not contradict. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:9468139 We find that Rb can recruit histone deacetylase to E2F and that Rb cooperates with HDAC1 to repress the E2F-regulated promoter of the gene encoding the cell-cycle protein cyclin E.
GO:0005515 protein binding	IPI PMID:9468140 Retinoblastoma protein represses transcription by recruiting...	MODIFY	Summary: Magnaghi-Jaulin et al. 1998: HDAC1 physically interacts with Rb (LXCXE motif) and cooperates in repression of E2F1-recruited promoters. Reason: As for PMID:9468139: GO:0042826 is the informative term for the E2F1-HDAC1 (Rb-bridged) relationship; generic protein binding is uninformative. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:9468140 Rb, which is recruited to target promoters by E2F1, represses transcription by masking the E2F1 transactivation domain and by inhibiting surrounding enhancer elements
GO:0005634 nucleus	IDA PMID:12717439 Chk2 activates E2F-1 in response to DNA damage.	ACCEPT	Summary: Phosphorylated E2F1 localizes to discrete nuclear structures after DNA damage (Stevens et al. 2003). Reason: Canonical nuclear localization. Supporting Evidence: PMID:12717439 A Chk2 consensus phosphorylation site in E2F-1 is phosphorylated in response to DNA damage, resulting in protein stabilization, increased half-life, transcriptional activation and localization of phosphorylated E2F-1 to discrete nuclear structures.
GO:0005634 nucleus	IDA PMID:1531329 The interaction of RB with E2F coincides with an inhibition ...	ACCEPT	Summary: E2F-pRB complex formation and transcriptional assays (Hiebert et al. 1992); E2F is a nuclear transcription factor. Reason: Canonical nuclear localization. Supporting Evidence: PMID:1531329 Assays of transcription from the adenovirus E2 promoter in transfection experiments demonstrate that formation of the complex containing pRB and E2F coincides with an inhibition of E2F-dependent transcriptional activity.
GO:0005634 nucleus	IDA PMID:20040599 Regulation of E2F1-induced apoptosis by the nucleolar protei...	ACCEPT	Summary: E2F1-RRP1B interaction observed in the nucleolus and nucleoplasmic punctates (Paik et al. 2010). Reason: Canonical nuclear localization. Supporting Evidence: PMID:20040599 Interaction between RRP1B and E2F1 can be found inside the nucleolus and diffuse nucleoplasmic punctates.
GO:0005634 nucleus	IDA PMID:28992046 Phosphorylated E2F1 is stabilized by nuclear USP11 to drive ...	ACCEPT	Summary: Nuclear USP11 deubiquitinates E2F1 in the nucleus, where E2F1 drives Peg10 transcription (Wang et al. 2018); GOA records this as is_active_in. Reason: Canonical nuclear localization where E2F1 is active. Supporting Evidence: PMID:28992046 which removes K63-linked ubiquitin chains thereby preventing E2F1 degradation in the nuclei.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA (UniProt subcellular-location keyword and mouse ortholog) for nucleus. Reason: Canonical nuclear localization, supported by multiple IDA rows. Supporting Evidence: file:human/E2F1/E2F1-uniprot.txt SUBCELLULAR LOCATION: Nucleus
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: Human Protein Atlas immunofluorescence curation places E2F1 in the nucleoplasm. Reason: Consistent with all other nuclear evidence; nucleoplasm is the compartment in which E2F1 acts on chromatin.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187937	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-187937 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187959	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-187959 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3209096	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-3209096 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3240765	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-3240765 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3240766	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-3240766 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3240777	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-3240777 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-4331324	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-4331324 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-4331327	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-4331327 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-4395231	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-4395231 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6798353	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-6798353 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8953556	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8953556 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961620	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961620 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961636	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961636 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961651	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961651 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961671	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961671 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961688	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961688 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961840	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961840 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961863	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961863 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961888	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961888 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961907	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961907 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961920	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961920 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961946	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961946 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8961961	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-8961961 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9007514	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-9007514 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9007561	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-9007561 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9018017	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-9018017 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9618586	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-9618586 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9659782	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-HSA-9659782 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005654 nucleoplasm	TAS Reactome:R-NUL-8963657	ACCEPT	Summary: TAS nucleoplasm annotation from Reactome event R-NUL-8963657 (E2F1-containing transcription events in the cell-cycle/G1-S, DNA-damage and apoptosis pathways). E2F1 is a nuclear, chromatin-associated transcription factor. Reason: Nucleoplasm is the canonical compartment of E2F1 activity; each Reactome event is a separate record of the same localization and all are consolidated to ACCEPT (RB1 review precedent).
GO:0005667 transcription regulator complex	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA for transcription regulator complex; E2F1 functions as the E2F1-DP heterodimer (DRTF1/E2F complex). Reason: Correct: the E2F1-DP1 heterodimer is a Pol II transcription regulator complex (child GO:0090575 annotated by IPI). Supporting Evidence: file:human/E2F1/E2F1-uniprot.txt SUBUNIT: Component of the DRTF1/E2F transcription factor complex. Forms
GO:0005737 cytoplasm	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl Compara transfer from mouse E2f1 of cytoplasmic localization. E2F1 carries an N-terminal NLS and is predominantly nuclear; cytoplasmic pools are reported only in some tumour/differentiation contexts and reflect trafficking or stability regulation. Reason: Not contradicted (E2F1 shuttles and can be detected in the cytoplasm), but it is not where E2F1 functions. Retained as a minor, non-core localization. Supporting Evidence: file:human/E2F1/E2F1-deep-research-falcon.md Reports of cytoplasmic regulatory interactions concern trafficking or stability and do not replace the nucleus as its principal functional compartment.
GO:0006351 DNA-templated transcription	IEA GO_REF:0000107	MODIFY	Summary: Ensembl Compara transfer from mouse E2f1 of 'DNA-templated transcription'. E2F1 is a transcription factor that regulates, but does not itself carry out, transcription. Reason: GO convention places sequence-specific transcription factors under 'regulation of transcription by RNA polymerase II' (GO:0006357), not under the transcription process itself, which is performed by the polymerase and general machinery. Replace with the Pol II regulation term already annotated. Proposed replacements: regulation of transcription by RNA polymerase II
GO:0006351 DNA-templated transcription	ISS GO_REF:0000024	MODIFY	Summary: Manual ISS transfer from mouse E2f1 of 'DNA-templated transcription'. Reason: Same reasoning as the IEA row: E2F1 regulates Pol II transcription of specific gene sets rather than executing transcription. Replace with GO:0006357. Proposed replacements: regulation of transcription by RNA polymerase II
GO:0006355 regulation of DNA-templated transcription	IDA PMID:12717439 Chk2 activates E2F-1 in response to DNA damage.	MODIFY	Summary: CHK2 phosphorylation of E2F1 leads to transcriptional activation (Stevens et al. 2003). E2F1 is a Pol II sequence-specific activator; the generic term is correct but uninformative relative to the RNA polymerase II-specific terms already present. Reason: Too general; replace with the RNA polymerase II-specific positive-regulation term that matches E2F1's demonstrated activity. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:12717439 A Chk2 consensus phosphorylation site in E2F-1 is phosphorylated in response to DNA damage, resulting in protein stabilization, increased half-life, transcriptional activation and localization of phosphorylated E2F-1 to discrete nuclear structures.
GO:0006355 regulation of DNA-templated transcription	IDA PMID:1531329 The interaction of RB with E2F coincides with an inhibition ...	MODIFY	Summary: Hiebert et al. 1992: formation of the E2F-pRB complex coincides with inhibition of E2F-dependent transcription from the adenovirus E2 promoter; a pRB mutant that cannot bind E2F does not inhibit. Classic demonstration that E2F is a transcription activator negatively regulated by RB1. Reason: The experiment shows E2F-dependent Pol II transactivation and its pRB-mediated inhibition; the generic term is superseded by the Pol II-specific GO:0006357 / GO:0045944 terms that E2F1 already carries. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:1531329 Assays of transcription from the adenovirus E2 promoter in transfection experiments demonstrate that formation of the complex containing pRB and E2F coincides with an inhibition of E2F-dependent transcriptional activity.
GO:0006355 regulation of DNA-templated transcription	IDA PMID:23934193 Pleiotropic effect of somatic mutations in the E2F subunit D...	MODIFY	Summary: Munro et al. 2014 show that cancer-associated DP-1 mutants transdominantly alter the DNA-binding, transactivation and pRB-binding properties of the E2F1/DP1 heterodimer and impair E2F1-dependent apoptosis - i.e. the heterodimer's transcriptional activity was assayed. Reason: Generic parent; the Pol II-specific term GO:0006357 (already annotated by IBA/IEA) is the appropriate level for the E2F1/DP1 heterodimer's activity. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:23934193 This allows the mutant derivatives to affect the properties of the E2F-1/DP-1 heterodimer through a transdominant mechanism, which changes the DNA binding, transcriptional activation and pRb-binding properties of the heterodimer.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO mapping from the E2F/DP winged-helix DNA-binding domain (IPR003316) to the generic 'regulation of DNA-templated transcription'. Correct at the family level, but E2F1 acts specifically on RNA polymerase II promoters. Reason: Handled consistently with the three IDA rows on this same term: the generic parent is superseded by GO:0006357 (regulation of transcription by RNA polymerase II), which E2F1 already carries by IBA and IEA. Every characterised E2F1 target is a Pol II gene, so the Pol II-specific term loses no coverage. Proposed replacements: regulation of transcription by RNA polymerase II
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: PAINT-inferred regulation of transcription by RNA polymerase II for the E2F family node, drawing on experimental annotations of fly E2f1/E2f2, mouse E2f1-4 and human E2F1-6 (E2F1 itself among the descendants). E2F1 is the prototypical Pol II-specific activator. Reason: Sound phylogenetic placement: sequence-specific Pol II transcription regulation is the ancestral, defining activity of the E2F family. The target's own experimental annotation appearing in WITH/FROM is expected. Core function. Supporting Evidence: file:human/E2F1/E2F1-uniprot.txt Transcription activator that binds DNA cooperatively with DP
GO:0006357 regulation of transcription by RNA polymerase II	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA (ARBA + InterPro E2F family IPR015633) for regulation of transcription by RNA polymerase II. Reason: Canonical E2F1 function, independently supported by IBA and by direct experimental rows (GO:0045944 IDA/IMP).
GO:0007283 spermatogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl Compara transfer from rat E2f1 of spermatogenesis. E2f1-null mice show testicular atrophy/germ-cell loss, reflecting E2F1's proliferative and apoptotic control in spermatogonia. Reason: A tissue-level phenotype downstream of E2F1's cell-cycle/apoptosis program in the germ line, not a distinct molecular activity. Retained as non-core.
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage	IMP PMID:12717439 Chk2 activates E2F-1 in response to DNA damage.	ACCEPT	Summary: CHK2-dependent phosphorylation stabilizes E2F1 after etoposide-induced DNA damage and is required for E2F1-dependent apoptosis (Stevens et al. 2003). Together with the p73/ASPP/DIP/RRP1B target-gene literature elsewhere in this review, this is the canonical DNA-damage-triggered, E2F1-driven intrinsic apoptotic program (both p53-dependent via ARF and p53-independent via TP73, BBC3 and others). Reason: E2F1 does the work of this pathway: stabilized E2F1 directly transactivates pro-apoptotic genes (TP73, ASPP1/2 [PMID:15731768], DIP [PMID:15565177], RRP1B [PMID:20040599]). The DNA-damage-responsive, pro-apoptotic transactivation is one of the two established physiological outputs of E2F1 and is captured in core_functions[2]. Supporting Evidence: PMID:12717439 Expression of a dominant-negative Chk2 mutant blocks induction of E2F-1 and prevents E2F-1-dependent apoptosis. file:human/E2F1/E2F1-deep-research-falcon.md Excessive or deregulated E2F1 can instead engage ARF–MDM2–p53 and p53-independent apoptotic programs.
GO:0010628 positive regulation of gene expression	IDA PMID:15766563 E2F1 up-regulates the expression of the tumour suppressor ax...	MODIFY	Summary: Hughes & Brady 2005 show E2F1 up-regulates AXIN2 both by direct transcriptional activation at canonical E2F sites of one 5'-UTR variant and by stabilizing axin2 mRNA. Reason: 'Positive regulation of gene expression' is a catch-all covering both mechanisms reported. The transcriptional mechanism is E2F1's core activity and is better captured by GO:0045944; the mRNA-stabilization mechanism is handled by the separate GO:0048255 row. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:15766563 The human axin2 gene allows transcription of messages with three different 5' untranslated regions and in the first mechanism E2F1 directly activates the transcription of only one of these species by acting at canonical E2F binding sites. Second, E2F1 induces stabilisation of axin2 mRNAs.
GO:0019901 protein kinase binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl Compara transfer from rat E2f1 of protein kinase binding. Human E2F1 is a documented substrate/partner of cyclin A-CDK2 (residues 67-108 bind cyclin A), CHK2, GSK3B and CDK8. Reason: Genuine: E2F1 binds cyclin A-CDK2 via a dedicated N-terminal motif and CDK8 (PMID:18794899). A regulatory-input interaction rather than a core activity; kept as non-core. Supporting Evidence: file:human/E2F1/E2F1-uniprot.txt Phosphorylated by CDK2 and cyclin A-CDK2 in the S-phase
GO:0032496 response to lipopolysaccharide	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl Compara transfer from mouse E2f1 of 'response to lipopolysaccharide' (the mouse annotation derives from a Reg3g/microglia GO-CAM, gocams/6348a65d00001191). Reason: A context-specific mouse observation (E2f1 activity in LPS-challenged microglia) propagated to human without human evidence; response-to-stimulus terms of this kind describe experimental context rather than E2F1 function.
GO:0032991 protein-containing complex	IDA PMID:23629655 Mixed lineage leukemia 5 (MLL5) protein regulates cell cycle...	MODIFY	Summary: Zhou et al. 2013: MLL5 associates with HCF-1 and E2F1-responsive promoters; E2F1 is found in an HCF-1-containing complex (UniProt: interaction with KMT2E is probably indirect via HCFC1). Reason: The root term 'protein-containing complex' is uninformative. The complex characterized is a Pol II transcription regulator assembly at E2F1 target promoters (E2F1-HCF-1-MLL5), so GO:0090575 is the informative term. Proposed replacements: RNA polymerase II transcription regulator complex Supporting Evidence: PMID:23629655 Conclusion: MLL5 stimulates H3K4 trimethylation at E2F1 responsive promoters and cause transcriptional activation of E2F1 target genes to facilitate the G 1 to S phase transition.
GO:0035189 Rb-E2F complex	IBA GO_REF:0000033	ACCEPT	Summary: PAINT-inferred Rb-E2F complex membership at the activator-E2F node (E2F1 itself is the experimental descendant). Hypophosphorylated RB1 binds the E2F1 transactivation domain and the E2F1-DP1 marked boxes. Reason: Namesake complex of E2F1 (first cloned as RBBP3/RBAP1); directly supported by crystal structures (PMID:12598654, PMID:16360038) and IDA. Core. Supporting Evidence: file:human/E2F1/E2F1-uniprot.txt SUBUNIT: Component of the DRTF1/E2F transcription factor complex. Forms
GO:0035189 Rb-E2F complex	IDA PMID:20224733 E2F-1 has dual roles depending on the cell cycle.	ACCEPT	Summary: Co-IP of E2F1 with pRB in cycling fibroblasts; the Y411C mutant does not form the complex. Reason: Direct evidence for the Rb-E2F complex; canonical. Supporting Evidence: PMID:20224733 E2F-1 acts as part of the repression complex with pRB in the expression of DHFR, b-myb, TK and cdc2 in asynchronously growing cells; on the other hand, E2F-1 acts as an activator in the expression of the same genes in cells that are re-entering the cycle.
GO:0035189 Rb-E2F complex	IPI PMID:16360038 Structure of the Rb C-terminal domain bound to E2F1-DP1: a m...	ACCEPT	Summary: RbC-E2F1-DP1 crystal structure (Rubin et al. 2005). Reason: Atomic-resolution demonstration of the Rb-E2F complex; canonical. Supporting Evidence: PMID:16360038 The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC.
GO:0043065 positive regulation of apoptotic process	IDA PMID:15565177 A novel mitochondrial protein DIP mediates E2F1-induced apop...	ACCEPT	Summary: Stanelle et al. 2005 identify DIP (KIAA0767, now DIP/CCDC?) as a p53-independent transcriptional target of E2F1 whose mitochondrial accumulation mediates E2F1-induced apoptosis; DIP siRNA rescues p53-null cells from E2F1-induced death. Demonstrates that E2F1 activation is sufficient to induce apoptosis through direct target-gene transactivation. Reason: E2F1-induced apoptosis via direct pro-apoptotic target genes is a well-established E2F1 output (TP73, APAF1, caspases, BBC3, DIP). GO:0043065 is the generic parent; the more mechanistic GO:0008630 row (PMID:12717439) sits alongside it, and both are retained as the apoptotic arm captured in core_functions[2]. Supporting Evidence: PMID:15565177 Yet, inhibition of endogenous DIP function by small interfering RNA rescued p53-negative cells from E2F1-induced apoptosis, indicating that DIP is an essential mediator of the p53-independent E2F1 death pathway. PMID:15565177 Endogenous DIP levels increased following E2F1 activation.
GO:0043392 negative regulation of DNA binding	IDA PMID:20176812 Repression of transcriptional activity of C/EBPalpha by E2F-...	ACCEPT	Summary: Gel-shift assays show that addition of the E2F1-DP1 complex diminishes C/EBPalpha association with DNA whereas E2F1 or DP1 alone barely do; the E2F1 L132E mutant loses C/EBPalpha repression. Reason: Direct in vitro demonstration that the E2F1-DP heterodimer inhibits DNA binding of another transcription factor - the precise molecular description of the C/EBPalpha antagonism. Accepted as a documented, though non-core, activity of the heterodimer (see core_functions note on lineage-specific outputs). Supporting Evidence: PMID:20176812 addition of E2F1-DP1 complex diminished the association of C/EBPα with DNA, while individual addition of DP1 or E2F1 did only barely affect C/EBPα binding to DNA.
GO:0043565 sequence-specific DNA binding	IDA PMID:23332764 DNA-binding specificities of human transcription factors.	ACCEPT	Summary: Jolma et al. 2013 HT-SELEX derived sequence-specific binding models for hundreds of human TFs including E2F1 (E2F-DP consensus TTTSSCGC-like motif). Reason: Direct in vitro determination of E2F1 sequence specificity; consistent with the E2F consensus. Generic relative to GO:0000978 but correct. Supporting Evidence: PMID:23332764 We have analyzed the sequence-specific binding of human TFs using high-throughput SELEX and ChIP sequencing.
GO:0043565 sequence-specific DNA binding	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA from rat/mouse E2f1 orthologs for sequence-specific DNA binding. Reason: Correct; supported by direct SELEX data on human E2F1.
GO:0043565 sequence-specific DNA binding	ISS GO_REF:0000024	ACCEPT	Summary: Manual ISS transfer from mouse E2f1 of sequence-specific DNA binding. Reason: Correct; supported by direct evidence on the human protein.
GO:0045599 negative regulation of fat cell differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl Compara transfer from mouse E2f1: E2F1-DP represses C/EBPalpha and blocks 3T3-L1 adipogenesis (PMID:20176812, which used human E2F1 constructs in mouse cells). Reason: Supported by direct experiments (PMID:20176812), but a lineage-specific developmental output of the C/EBPalpha antagonism, not a core E2F1 function. Supporting Evidence: file:human/E2F1/E2F1-uniprot.txt Blocks adipocyte differentiation
GO:0045599 negative regulation of fat cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Manual ISS transfer from mouse E2f1 of negative regulation of fat cell differentiation (E2F-DP antagonism of C/EBPalpha). Reason: Lineage-specific developmental output; non-core. Supporting Evidence: file:human/E2F1/E2F1-uniprot.txt Blocks adipocyte differentiation
GO:0045892 negative regulation of DNA-templated transcription	IDA PMID:20176812 Repression of transcriptional activity of C/EBPalpha by E2F-...	KEEP AS NON CORE	Summary: Zaragoza et al. 2010 (full text): the E2F1-DP1 heterodimer binds C/EBPalpha via DP and disrupts C/EBPalpha binding to its cognate DNA sites, thereby repressing C/EBPalpha-dependent transcription of adipogenic target genes; the mechanism is pocket-protein independent. Reason: A genuine but indirect repression: E2F1-DP sequesters a different DNA-binding TF rather than repressing via its own DNA binding. It is a lineage-specific (adipogenic/granulocytic) regulatory role, not the core E2F-site-driven transcription program. GO:0043392 (negative regulation of DNA binding) from the same paper is the more precise description of what E2F1-DP does. Supporting Evidence: PMID:20176812 E2F represses the transactivation of C/EBPα target genes by disrupting the binding of C/EBPα to its cis -regulatory sites.
GO:0045893 positive regulation of DNA-templated transcription	IDA PMID:21454377 MiR-15 and miR-16 are direct transcriptional targets of E2F1...	MODIFY	Summary: Ofir et al. 2011: endogenous E2F1 binds the miR-15a/16-1 and miR-15b/16-2 cluster promoters and induces their expression (pri-miRNA and mature miR levels rise on E2F1 activation), forming a feed-forward loop that limits cyclin E. Reason: Correct but too general: these are RNA polymerase II-transcribed miRNA host loci, so GO:0045944 (positive regulation of transcription by RNA polymerase II) is the appropriate, already-annotated level. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:21454377 Moreover, activation of endogenous E2Fs upregulates expression of these miRs and endogenous E2F1 binds their respective promoters. PMID:21454377 We show that expression levels of the 4 mature miRs, miR-15a, miR-16-1 and miR-15b, miR-16-2, as well as their precursor pri-miRNAs, are elevated upon activation of ectopic E2F1.
GO:0045893 positive regulation of DNA-templated transcription	IDA PMID:22476863 E2F1 induces p19INK4d, a protein involved in the DNA damage ...	MODIFY	Summary: Carcagno et al. 2012: UV-induced transcriptional induction of p19INK4d (CDKN2D) requires E2F1 (ablation and DNA-binding inhibition prevent it) and E2F response elements in the CDKN2D promoter (triplex-forming oligonucleotides block induction). Reason: Direct E2F-site-dependent activation of a Pol II gene; the RNA polymerase II-specific child GO:0045944 is the appropriate term and is already annotated. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:22476863 Moreover, evidence is presented that demonstrates that E2F1 is involved in the induction of p19INK4d following UV treatment, as it is prevented by E2F1 protein ablation and DNA-binding inhibition.
GO:0045893 positive regulation of DNA-templated transcription	IMP PMID:15565177 A novel mitochondrial protein DIP mediates E2F1-induced apop...	MODIFY	Summary: Same paper: DIP is a direct E2F1 transcriptional target whose endogenous levels rise upon E2F1 activation. Positive regulation of DNA-templated transcription is correct but far less specific than the RNA polymerase II-specific activator terms E2F1 already carries. Reason: E2F1 is a sequence-specific RNA polymerase II transcription activator; the child term GO:0045944 (positive regulation of transcription by RNA polymerase II) is the appropriate level and is already annotated (PMID:28992046 IDA, PMID:20040599 IMP). The generic parent adds no information. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:15565177 Endogenous DIP levels increased following E2F1 activation.
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:28992046 Phosphorylated E2F1 is stabilized by nuclear USP11 to drive ...	ACCEPT	Summary: Wang et al. 2018 show that GSK3B-phosphorylated E2F1 is deubiquitinated and stabilized by nuclear USP11, and that E2F1 protein levels directly control Peg10 mRNA; PEG10 is a previously established direct E2F1 target. Reason: Direct transactivation of a Pol II target gene (PEG10) by E2F1 - canonical activator function. Supporting Evidence: PMID:28992046 Downregulation of USP11 increases E2F1 ubiquitination and reduces E2F1 stability and protein levels, thereby decreasing Peg10 mRNA levels.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:20040599 Regulation of E2F1-induced apoptosis by the nucleolar protei...	ACCEPT	Summary: Paik et al. 2010 characterize the RRP1B promoter as an E2F1-specific transcriptional target induced by DNA damage; RRP1B in turn co-operates with E2F1 on pro-apoptotic promoters. Reason: Direct, promoter-level transactivation of a Pol II target gene by E2F1. Supporting Evidence: PMID:20040599 We now identify a nucleolar protein, RRP1B, as an E2F1-specific transcriptional target. We characterize the RRP1B promoter and demonstrate its selective response to E2F1.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:20224733 E2F-1 has dual roles depending on the cell cycle.	ACCEPT	Summary: In the same study, E2F1 (wild-type and free E2F1-411) activates DHFR, b-myb, TK and cdc2 in cells re-entering the cell cycle from quiescence, and E2F1 over-expression is sufficient to drive quiescent cells into S phase. Reason: Canonical E2F1 function: activation of Pol II-transcribed G1/S genes once free of pRB. Captured in core_functions[0]. Supporting Evidence: PMID:20224733 E2F-1 acts as part of the repression complex with pRB in the expression of DHFR, b-myb, TK and cdc2 in asynchronously growing cells; on the other hand, E2F-1 acts as an activator in the expression of the same genes in cells that are re-entering the cycle. PMID:20224733 Overexpression of E2F-1 is sufficient to induce S-phase in most quiescent cells, as reported previously 30, 31.
GO:0046983 protein dimerization activity	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO mapping from the E2F coiled-coil/marked-box dimerization domain (IPR032198). E2F1 obligately heterodimerizes with TFDP1/2 through this region. Reason: Correct but the E2F1 dimerization is specifically heterodimerization with DP partners (crystal structure PMID:16360038); the child term GO:0046982 (protein heterodimerization activity) is more informative. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:16360038 The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC.
GO:0048146 positive regulation of fibroblast proliferation	IMP PMID:20224733 E2F-1 has dual roles depending on the cell cycle.	KEEP AS NON CORE	Summary: Over-expression of E2F1 in the murine psi-CRE fibroblast line decreased the G1 fraction, accelerated S-phase entry and increased soft-agar colony formation. This is the cellular phenotype of E2F1-driven G1/S transcription rather than a distinct fibroblast-specific function. Reason: Fibroblast proliferation is a downstream cellular read-out of E2F1's core G1/S transcriptional program (GO:2000045 / GO:0045944 rows from the same paper). Not wrong, but a cell-type-specific phenotype term rather than a core function; retained as non-core. Supporting Evidence: PMID:20224733 It was found that the overexpression of E2F-1/wt and E2F-1/411 significantly decreased the cell number in G1 phase compared to the control (pX17) cells.
GO:0048255 mRNA stabilization	IDA PMID:15766563 E2F1 up-regulates the expression of the tumour suppressor ax...	MARK AS OVER ANNOTATED	Summary: The same study reports that E2F1 induces stabilisation of axin2 mRNAs by an unspecified, transcription-independent mechanism. E2F1 has no RNA-binding domain and no known direct role in mRNA turnover; the effect is most parsimoniously explained by E2F1-dependent transcription of an RNA-binding regulator. Reason: The observation (abstract-only cache) is a downstream phenotype; the authors do not show E2F1 acting on the mRNA. Per the participation test, E2F1 does not do the work of mRNA stabilization, so this single-observation annotation over-reaches. Not REMOVE because the experimental result is not contradicted, but it should not be propagated. Supporting Evidence: PMID:15766563 The human axin2 gene allows transcription of messages with three different 5' untranslated regions and in the first mechanism E2F1 directly activates the transcription of only one of these species by acting at canonical E2F binding sites. Second, E2F1 induces stabilisation of axin2 mRNAs.
GO:0060090 molecular adaptor activity	EXP PMID:16360038 Structure of the Rb C-terminal domain bound to E2F1-DP1: a m...	KEEP AS NON CORE	Summary: Rubin et al. 2005 crystal structure of RbC bound to the E2F1-DP1 heterodimer: the marked-box domains of both E2F1 and DP1 contact RbC, and the E2F1 transactivation domain independently binds the Rb pocket. E2F1 thereby physically tethers RB1 (and its corepressors) to E2F-site chromatin. Reason: E2F1 does bridge RB1 to promoter DNA (the recruiter of the Rb-E2F repressor complex), so an adaptor description is defensible for the repression context. However E2F1's defining activity is sequence-specific transcription factor activity, and the same structural evidence is already captured by GO:0035189 (Rb-E2F complex) and GO:0140297; the adaptor term is kept as a non-core description of the repressed state. Supporting Evidence: PMID:16360038 The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC. PMID:16360038 Here we demonstrate a high-affinity interaction between RbC and E2F-DP heterodimers shared by all Rb and E2F family members.
GO:0060252 positive regulation of glial cell proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl Compara transfer from rat E2f1 of positive regulation of glial cell proliferation. Reason: A cell-type instance of E2F1's generic pro-proliferative G1/S program; not wrong but non-core.
GO:0070345 negative regulation of fat cell proliferation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl Compara transfer of negative regulation of fat cell proliferation from mouse E2f1. Reason: E2F1 is a positive regulator of proliferation; the adipocyte data (PMID:20176812) concern blocked differentiation via C/EBPalpha, not fat cell proliferation. Likely a mis-scoped mouse annotation propagated electronically.
GO:0070345 negative regulation of fat cell proliferation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Manual ISS transfer of negative regulation of fat cell proliferation from mouse E2f1. Reason: Same concern as the IEA row: the underlying experiments address adipocyte differentiation, and E2F1 promotes rather than restrains proliferation.
GO:0071398 cellular response to fatty acid	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl Compara transfer from rat E2f1 of cellular response to fatty acid. Reason: Rat-specific expression/response observation propagated without human evidence; describes experimental context, not E2F1 function.
GO:0071456 cellular response to hypoxia	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl Compara transfer from rat E2f1 of cellular response to hypoxia. Reason: Context-specific rat observation; E2F1 levels change under many stresses, but this is not a defined E2F1 function.
GO:0090575 RNA polymerase II transcription regulator complex	IPI PMID:16360038 Structure of the Rb C-terminal domain bound to E2F1-DP1: a m...	ACCEPT	Summary: Crystal structure of the E2F1-DP1 heterodimer (with RbC) - the DNA-binding E2F transcription factor complex. Reason: The E2F1-TFDP1 heterodimer is the functional Pol II transcription regulator complex; core in_complex for core_functions[0]. Supporting Evidence: PMID:16360038 The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC.
GO:0140297 DNA-binding transcription factor binding	IPI PMID:16360038 Structure of the Rb C-terminal domain bound to E2F1-DP1: a m...	ACCEPT	Summary: Structural demonstration of the E2F1-TFDP1 heterodimer (intertwined coiled-coil/marked-box dimer) bound to RbC. Reason: TFDP1 is a DNA-binding transcription factor and the obligate heterodimeric partner of E2F1; this is the informative binding term for the E2F1-DP interaction and underlies core_functions[0]. Supporting Evidence: PMID:16360038 The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC.
GO:0140297 DNA-binding transcription factor binding	IPI PMID:20176812 Repression of transcriptional activity of C/EBPalpha by E2F-...	ACCEPT	Summary: Co-IP and in vitro binding show the E2F1-DP complex binds C/EBPalpha (bZIP domain) and blocks its DNA binding; the E2F1 L132E mutant loses the interaction. Reason: C/EBPalpha is a DNA-binding TF; the interaction is functionally characterized (GO:0043392 row). Informative binding term; non-core lineage-specific context. Supporting Evidence: PMID:20176812 E2F represses the transactivation of C/EBPα target genes by disrupting the binding of C/EBPα to its cis -regulatory sites.
GO:1990090 cellular response to nerve growth factor stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl Compara transfer from rat E2f1 of cellular response to nerve growth factor stimulus. Reason: Rat PC12-type observation propagated electronically; experimental context rather than function.
GO:1990837 sequence-specific double-stranded DNA binding	IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ...	ACCEPT	Summary: Yin et al. 2017 methyl-SELEX: sequence-specific double-stranded DNA binding of human TFs including E2F1, with characterisation of CpG-methylation sensitivity (E2F sites are CpG-containing). Reason: Direct in vitro evidence for sequence-specific dsDNA binding by E2F1. Supporting Evidence: PMID:28473536 The majority of CpG dinucleotides in the human genome are methylated at cytosine bases.
GO:2000045 regulation of G1/S transition of mitotic cell cycle	IMP PMID:20224733 E2F-1 has dual roles depending on the cell cycle.	ACCEPT	Summary: E2F1 over-expression is sufficient to induce S phase in quiescent fibroblasts and reduces the G1 fraction of cycling cells; E2F1 activates the G1/S gene cluster (cyclin E, CDC6, CDT1, MCMs, TK, DHFR, b-myb, cdc2) once released from pRB. GOA records this row with acts_upstream_of, consistent with E2F1 acting through transcription of cyclin E/CDK2 regulators. Reason: Control of the G1/S transition is the defining physiological role of the activator E2Fs (E2F1-3) and of E2F1 in particular. Captured in core_functions[0]; the direction (positive) is unambiguous from this and many other studies. Supporting Evidence: PMID:20224733 Overexpression of E2F-1 is sufficient to induce S-phase in most quiescent cells, as reported previously 30, 31. file:human/E2F1/E2F1-deep-research-falcon.md The best-established physiological role is activation of a coordinated proliferation program at the G1/S transition.

Gene Description

Existing Annotations Review

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References

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Deep Research

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