Affinage

E2F1

Transcription factor E2F1 · UniProt Q01094

Length
437 aa
Mass
46.9 kDa
Annotated
2026-06-09
100 papers in source corpus 39 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

E2F1 is a sequence-specific transcription factor that operates downstream of the CDK4-RB axis to drive proliferative, apoptotic, and metabolic gene programs, with its activity dictated by both heterodimerization and an extensive post-translational modification code (PMID:8207796, PMID:26619117). DNA binding requires heterodimerization with DP1 through reciprocal hydrophobic heptad-repeat domains, and the E2F1-DP1 complex resists the degradation and nucleolar relocalization that ARF imposes on free E2F1 monomers (PMID:8207796, PMID:12446760). A dense PTM network sets E2F1 abundance and target selection: P/CAF acetylation near the DNA-binding domain raises DNA-binding affinity, transactivation, and stability and is reversed by RB-associated/HDAC1 deacetylation, while Set9 methylation at K185 and PRMT5 arginine methylation destabilize E2F1 and curb its proapoptotic output, with LSD1 demethylation and DNA-damage signals reversing this restraint (PMID:10675335, PMID:20603083, PMID:22327218, PMID:25816777). Protein turnover is controlled by competing ubiquitin machinery—SCF(SKP2) and APC/C(Cdc20) promote degradation, MDM2 stabilizes E2F1 by displacing SCF(SKP2), and the deubiquitylases POH1 and methyl-dependent CRL4(DCAF5) recruitment via L3MBTL3 further tune levels (PMID:16170383, PMID:26510456, PMID:20948288, PMID:29691401). Genotoxic stress stabilizes and activates E2F1 through ATM/ATR phosphorylation at Ser31, which is required for recruitment to damage sites, DNA repair, and tumor suppression, and through an ATM/NBS1 axis that phosphorylates p53 and Chk2 to drive apoptosis (PMID:15140942, PMID:24741006). Beyond proliferation, E2F1 is a central metabolic regulator that binds promoters of lipogenic (Fasn), gluconeogenic (Pck1), cholesterol-handling (Pcsk9), and glycolytic genes and controls insulin secretion via Kir6.2, such that E2f1 loss protects against hepatic steatosis (PMID:19597485, PMID:26619117, PMID:28515357, PMID:29526568). Its proapoptotic versus prosurvival outcomes are shaped by interacting partners and feedback loops including SirT1, EZH2, p53, AHR, and SUMOylation/SENP3 (PMID:16892051, PMID:32541040, PMID:18524851, PMID:19893569, PMID:24076372).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1994 High

    Established the structural basis of E2F1 function by defining how it acquires DNA-binding competence through obligate heterodimerization with DP1.

    Evidence Yeast two-hybrid and co-IP with deletion mapping in SAOS-2 cells

    PMID:8207796

    Open questions at the time
    • Does not address regulation of the dimer in normal cell-cycle context
    • No structural model of the complex on DNA
  2. 2000 High

    Showed that acetylation is a direct activating switch on E2F1, linking enzyme-mediated modification to DNA binding, transactivation, and stability.

    Evidence In vitro P/CAF acetylation, site-directed mutagenesis, transcription assays

    PMID:10675335

    Open questions at the time
    • In vitro assays do not establish physiological stoichiometry
    • Did not resolve which lysines dominate in vivo
  3. 2004 High

    Positioned E2F1 upstream of the ATM/NBS1-p53 apoptotic axis, showing E2F1 activates this pathway by a route distinct from canonical double-strand breaks.

    Evidence ATM-deficient and NBS1-mutant primary fibroblasts with phosphorylation and apoptosis readouts

    PMID:15140942 PMID:15190206

    Open questions at the time
    • Mechanism by which E2F1 activates ATM without Ser1981 autophosphorylation unresolved
    • Does not identify direct E2F1-ATM contact
  4. 2005 High

    Defined opposing ubiquitin-pathway control of E2F1 stability, showing MDM2 stabilizes E2F1 by displacing its SCF(SKP2) ligase independent of p53 and pRB.

    Evidence Co-IP, ubiquitination and half-life assays with deletion mutants

    PMID:16170383

    Open questions at the time
    • Did not map the degron displaced by MDM2
    • In vivo relevance not tested genetically
  5. 2005 High

    Connected E2F1 to a c-Myc feedforward/feedback circuit in which Myc both activates E2F1 transcription and represses E2F1 translation via a miRNA cluster.

    Evidence ChIP at the miRNA locus and miRNA reporter assays for E2F1 repression

    PMID:15944709

    Open questions at the time
    • Quantitative balance of activation vs repression in vivo unclear
  6. 2009 High

    Demonstrated that E2F1 is a direct transcriptional regulator of metabolic genes controlling insulin secretion, extending its role beyond proliferation.

    Evidence ChIP from pancreatic tissue, E2f1 knockout mice, Kir6.2 rescue, glucose tolerance tests

    PMID:19597485

    Open questions at the time
    • Does not address coordination with cell-cycle target program
  7. 2010 High

    Showed that lysine methylation by Set9 acts as a degradation-promoting brake on DNA-damage-induced E2F1 stabilization and apoptosis, reversed by LSD1.

    Evidence In vitro methylation, mutagenesis, siRNA, co-IP, apoptosis assays

    PMID:20603083

    Open questions at the time
    • Crosstalk hierarchy among PTMs only partially mapped
    • Reader of K185 methylation not identified here
  8. 2010 Medium

    Identified cell-cycle-phase-specific destruction of E2F1 by APC/C(Cdc20) in prometaphase, blocked by DP1 co-expression.

    Evidence Cell synchronization, Cdc20 overexpression/knockdown, stability assays

    PMID:20948288

    Open questions at the time
    • Degron recognized by APC/C not mapped
    • Single lab, no reciprocal in vivo validation
  9. 2012 High

    Showed arginine methylation by PRMT5 destabilizes E2F1 and limits its DNA binding, with DNA damage relieving this mark to enable proapoptotic function.

    Evidence In vitro methylation, PRMT5 siRNA, stability and DNA-binding assays

    PMID:22327218

    Open questions at the time
    • Specific arginine residues and crosstalk with K185 methylation not fully resolved
  10. 2014 High

    Established that ATM/ATR phosphorylation at Ser31 is required in vivo for E2F1-dependent DNA repair and tumor suppression.

    Evidence S29A knock-in mice, UV experiments, ChIP at damage sites, tumor incidence

    PMID:24741006

    Open questions at the time
    • Mechanism of recruitment to damage sites not molecularly defined
  11. 2015 High

    Defined E2F1 as a master driver of hepatic lipogenesis and glycolysis acting downstream of feeding/insulin via CDK4-pRB.

    Evidence ChIP-Seq, E2f1 knockout mice, NAFLD models, primary hepatocytes

    PMID:26619117

    Open questions at the time
    • Does not separate transcriptional from cell-cycle effects on metabolism
  12. 2015 High

    Identified POH1 as a deubiquitylase that stabilizes E2F1, adding a counterweight to E2F1 ubiquitination in vivo.

    Evidence Co-IP, deubiquitylation assay, conditional Poh1 knockout liver

    PMID:26510456

    Open questions at the time
    • Which E2F1 ubiquitin marks POH1 removes not specified
  13. 2016 High

    Revealed citrullination by PAD4 as a modification that redirects E2F1 to cytokine promoters and recruits BRD4 to drive inflammatory transcription.

    Evidence In vitro citrullination, ChIP, co-IP, pharmacological inhibition, arthritis model

    PMID:26989780

    Open questions at the time
    • Citrullinated residues not mapped
    • Generalizability beyond inflammatory cells unclear
  14. 2017 High

    Extended E2F1's metabolic reach to cholesterol homeostasis by showing it transactivates PCSK9 to promote LDLR degradation.

    Evidence ChIP-Seq, PCSK9 reporter assays, E2f1 knockout mice, LDL uptake assays

    PMID:28515357

    Open questions at the time
    • Interaction with lipogenic program coordination not addressed
  15. 2018 Medium

    Showed methylation-dependent recruitment of CRL4(DCAF5) via the reader L3MBTL3 couples E2F1 methylation to its degradation.

    Evidence Biochemical methyl-binding and ubiquitination assays, genetic deletion models

    PMID:29691401

    Open questions at the time
    • Which methyl mark is read not pinned down
    • In vivo significance limited
  16. 2018 Medium

    Linked E2F1 to gluconeogenic control, showing it transcriptionally activates Pck1 and AUF1 through the CDK4-RB1-E2F1 pathway.

    Evidence ChIP, E2F1 overexpression/knockout, hepatocyte gluconeogenesis assays, diabetic mice

    PMID:29526568

    Open questions at the time
    • Single lab; coordination with lipogenic program not resolved
  17. 2020 High

    Identified SUMO2 conjugation at K266 as a stress-responsive brake that inhibits E2F1 transactivation to favor survival, reversed by SENP3.

    Evidence In vivo SUMOylation, K266 mutagenesis, co-IP, SENP3 knockdown, viability assays

    PMID:32541040

    Open questions at the time
    • How oxidative stress disrupts the E2F1-SENP3 interaction mechanistically unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dozens of competing PTMs, partner proteins, and feedback loops are integrated in real time to select between proliferative, apoptotic, and metabolic E2F1 target programs remains unresolved.
  • No integrated model linking PTM combinations to specific gene-program outputs
  • Stoichiometry and temporal order of modifications in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 3 GO:0005730 nucleolus 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1640170 Cell Cycle 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-73894 DNA Repair 2
Partners
AHRBRD4MDM2PTENRB1SIRT1TFDP1TP53
Complex memberships
E2F1-DP1 heterodimer

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 P/CAF acetylates E2F1 in vitro at lysine residues adjacent to the DNA-binding domain; acetylation increases E2F1 DNA-binding ability, transcriptional activation potential, and protein half-life. The RB-associated histone deacetylase can deacetylate E2F1, reversing these effects. In vitro acetylation assay, site-directed mutagenesis, intracellular acetylation detection, functional transcription assays The EMBO journal High 10675335
2006 SirT1 physically binds E2F1 and inhibits its transcriptional and apoptotic activities. E2F1 transcriptionally induces SirT1 expression, forming a negative feedback loop. Knockdown of SirT1 increases E2F1-dependent apoptosis and sensitivity to etoposide. Co-immunoprecipitation, siRNA knockdown, transcriptional reporter assays, apoptosis assays Nature cell biology High 16892051
2010 Set9 methyltransferase methylates E2F1 at lysine-185, which prevents E2F1 accumulation during DNA damage and suppresses proapoptotic target gene p73 activation. LSD1 demethylase removes this mark, stabilizing E2F1 and enabling apoptotic function. Methylation at K185 inhibits acetylation and phosphorylation at distant sites while stimulating ubiquitination and proteasomal degradation. In vitro methylation assay, site-directed mutagenesis, siRNA knockdown, co-immunoprecipitation, apoptosis assays Molecular cell High 20603083
2012 PRMT5 directly methylates E2F1 on arginine residues, promoting E2F1 protein stability reduction and decreased DNA-binding activity. Depleting PRMT5 causes increased E2F1 protein levels and apoptosis. DNA damage conditions reduce arginine methylation of E2F1, allowing its stabilization. In vitro methylation assay, PRMT5 depletion (siRNA), protein stability assays, DNA-binding assays, apoptosis assays The EMBO journal High 22327218
2005 MDM2 stabilizes E2F1 protein by inhibiting its ubiquitination; MDM2 displaces SCF(SKP2), the E2F1 E3 ubiquitin ligase, through direct binding to E2F1, thereby prolonging E2F1 half-life independent of p53 and pRB. Co-immunoprecipitation, ubiquitination assays, half-life measurement, deletion mutant analysis Oncogene High 16170383
2015 POH1 deubiquitylase binds to and deubiquitylates E2F1, stabilizing E2F1 protein. Conditional Poh1 knockout reduces E2F1 expression in primary mouse liver cells. Co-immunoprecipitation, deubiquitylation assay, conditional knockout mouse, western blot Nature communications High 26510456
2010 APC/C(Cdc20) ubiquitin ligase targets E2F1 for degradation specifically in prometaphase. Ectopic Cdc20 reduces E2F1 protein; Cdc20 knockdown causes E2F1 accumulation in prometaphase. Co-expression of DP1 with E2F1 blocks APC/C-induced E2F1 degradation. Co-expression experiments, siRNA knockdown, cell synchronization, western blot, protein stability assays Cell cycle Medium 20948288
2018 L3MBTL3 methyl-binding protein binds methylated E2F1 and recruits CRL4DCAF5 ubiquitin ligase to degrade E2F1 in a methylation-dependent manner, analogous to its regulation of DNMT1. Biochemical binding assays, ubiquitination/degradation assays, genetic deletion models Nature communications Medium 29691401
2016 PAD4 citrullinates E2F1 in inflammatory cells, which promotes E2F1 chromatin association at cytokine gene promoters. Citrullination augments binding of BRD4 to an acetylated domain of E2F1, and PAD4/BRD4/E2F1 coexist on cytokine gene promoters to drive inflammatory gene expression. Combined PAD4 and BRD4 inhibition disrupts this complex and suppresses cytokine expression. In vitro citrullination assay, ChIP, co-immunoprecipitation, pharmacological inhibition, murine arthritis model Science advances High 26989780
2020 SUMOylation of E2F1 at lysine-266 (SUMO2 conjugation) inhibits E2F1 transcriptional activity upon oxidative stress, promoting cell cycle arrest for cell survival. SENP3 desumoylase interacts with E2F1; oxidative stress inhibits E2F1-SENP3 interaction, leading to accumulation of sumoylated E2F1. In vivo SUMOylation assays, site-directed mutagenesis (K266), co-immunoprecipitation, SENP3 knockdown, cell viability assays Proceedings of the National Academy of Sciences of the United States of America High 32541040
2020 SUMOylation enhances E2F1 binding to the EZH2 promoter, increasing EZH2 transcription. Knockdown of SAE2 (SUMO-activating enzyme) or pharmacological inhibition of SUMOylation reduces E2F1 binding to the EZH2 promoter and decreases EZH2 mRNA and protein levels. SAE2 siRNA knockdown, pharmacological SUMOylation inhibition, ChIP, qRT-PCR, western blot Cancer research Medium 32816857
2004 E2F1 induces p53 phosphorylation and apoptosis through the ATM/NBS1 signaling pathway. In ATM-deficient primary human fibroblasts, E2F1-induced p53 phosphorylation and apoptosis are impaired. E2F1 also induces ATM- and NBS1-dependent phosphorylation of Chk2 at Thr68. ATM autophosphorylation at Ser1981 is absent, suggesting E2F1 activates ATM through a mechanism distinct from DNA double-strand breaks. Primary fibroblast studies with ATM-deficient and NBS1-mutant cells, phosphorylation assays (p53, Chk2, γH2AX), apoptosis assays Molecular cancer research High 15140942
2014 E2F1 is phosphorylated at serine 31 (mouse Ser29) by ATM or ATR in response to DNA damage, which promotes E2F1 protein stabilization and recruitment to sites of DNA damage. This phosphorylation is required for DNA repair and suppression of UV-induced carcinogenesis; S29A knock-in mice show reduced DNA repair and increased skin tumor susceptibility. Knock-in mouse model (S29A mutation), UV radiation experiments, DNA repair assays, ChIP at damage sites, tumor incidence measurement Cancer research High 24741006
2012 p38 MAPK-MK2 axis regulates E2F1 expression in response to epirubicin; MK2 directly phosphorylates E2F1 at Ser-364 in vitro, contributing to E2F1 induction by epirubicin. E2F1 in turn promotes FOXM1 expression. In vitro phosphorylation assay, pharmacological inhibitors, siRNA knockdown, knockout MEFs, transfection assays Molecular cancer research Medium 22802261
1994 E2F1 and DP1 heterodimerize through their hydrophobic heptad repeat domains (E2F1 residues 206–283 interacting with DP1 residues 196–245). The adenovirus E4 protein interacts with the DP1 subunit (not E2F1 directly) to stabilize the E2F1-DP1 complex on the E2 promoter. Yeast two-hybrid assay, co-expression/co-immunoprecipitation in SAOS-2 cells, deletion mutagenesis Journal of virology High 8207796
2002 ARF induces proteolysis of free E2F1 and relocalizes it to the nucleolus, inhibiting E2F1-activated transcription. However, the E2F1/DP1 heterodimer is refractory to ARF-induced relocalization or degradation; coexpression of DP1 prevents ARF from targeting E2F1. Co-immunoprecipitation, fluorescence microscopy (relocalization), protein stability/degradation assays, transcription reporter assays Molecular and cellular biology Medium 12446760
2008 E2F1 is a potent inhibitor of beta-catenin/TCF-dependent transcription in a GSK3/APC-independent manner. CDK8, a colorectal oncoprotein, phosphorylates/represses E2F1 activity, protecting beta-catenin transcription from E2F1-mediated inhibition. E2F1-induced apoptosis is partly mediated through suppression of beta-catenin activity. Genetic epistasis (Drosophila and mammalian cells), reporter assays, CDK8 overexpression/knockdown, E2F1 overexpression, apoptosis assays Nature High 18794899
2008 The aryl hydrocarbon receptor (AHR) physically interacts with E2F1 independently of RB (demonstrated by co-IP from RB-negative cell extracts). AHR and E2F1 co-occupy the Apaf1 promoter at an E2F1 binding site. AHR activation represses E2F1-dependent transcription of Apaf1 and TAp73, attenuating E2F1-induced apoptosis. Co-immunoprecipitation (RB-negative cells), ChIP, siRNA knockdown, apoptosis assays, reporter assays Molecular biology of the cell Medium 18524851
2009 E2F1 transcriptionally induces EZH2 expression; EZH2 in turn antagonizes E2F1-dependent Bim induction via histone methylation, suppressing E2F1's proapoptotic activity. RNAi depletion of EZH2 enhances E2F1-dependent Bim expression and promotes apoptosis. RNAi, reporter assays, western blot, apoptosis assays Cell death and differentiation Medium 19893569
2009 The CDK4-pRB-E2F1 pathway directly regulates Kir6.2 expression in pancreatic beta cells. E2F1 binds the Kir6.2 promoter (ChIP from tissues), and E2F1 genetic inactivation leads to decreased Kir6.2 expression, impaired insulin secretion, and glucose intolerance. CDK4 is activated by glucose through the insulin pathway to activate E2F1. ChIP from pancreatic tissue, E2f1 knockout mice, Kir6.2 rescue experiments, glucose tolerance tests, insulin secretion assays Nature cell biology High 19597485
2015 E2F1 directly binds to the promoters of lipogenic genes including Fasn in hepatocytes (ChIP-Seq confirmed); E2F1 deficiency reduces glycolysis and de novo fatty acid synthesis. E2F1 expression increases in response to feeding and insulin through CDK4/pRB pathway activation. E2f1 deletion abrogates hepatic steatosis in NAFLD mouse models. ChIP-Seq, E2f1 knockout mice, primary hepatocyte experiments, murine NAFLD models, reporter assays The Journal of clinical investigation High 26619117
2017 E2F1 binds to and transactivates the PCSK9 promoter (ChIP-Seq), increasing PCSK9 expression and thus promoting LDLR degradation to inhibit cholesterol clearance. E2f1 deletion leads to decreased Pcsk9 expression and increased LDLR expression and LDL uptake. ChIP-Seq, PCSK9 promoter reporter assays, E2f1 knockout mice, LDL uptake assays JCI insight High 28515357
2018 E2F1 directly binds the Sirt6 promoter and suppresses Sirt6 transcription, thereby enhancing glycolysis (increased glucose uptake and lactate production). A DNA-binding-deficient E2F1 mutant cannot enhance glycolysis. HDAC1 deacetylates E2F1 and diminishes its suppression of Sirt6; acetylated E2F1 binds the Sirt6 promoter more strongly. ChIP, Sirt6 promoter reporter assays, E2F1 overexpression with DNA-binding mutant, siRNA knockdown, glucose uptake/lactate assays, HDAC inhibitor treatment Oncotarget Medium 25816777
2018 E2F1 associates with DP1 to bind the KPNA2 promoter and induce KPNA2 expression. KPNA2, as a nuclear import factor, mediates nuclear localization of E2F1. E2F7 competes with DP1 to block E2F1-induced KPNA2 activation; mutation of E2F7 dimerization residues or E2F1 DNA-binding domain abolishes this competition. ChIP, promoter reporter assays, mutagenesis, co-immunoprecipitation, nuclear fractionation, siRNA knockdown Oncogene Medium 30254209
2013 p53 physically interacts with E2F1 upon DNA damage to form a p53-E2F1-DNA complex on the PLK1 promoter, repressing E2F1-dependent PLK1 transcription. Mutation of E2F1 binding sites in the PLK1 promoter abolishes p53-mediated suppression. Co-immunoprecipitation, EMSA, ChIP, re-ChIP, promoter deletion/substitution mutagenesis, reporter assays Experimental cell research Medium 24076372
2018 Nuclear PTEN (phosphorylation-deficient PTEN-4A mutant) physically interacts with E2F1 and associates with chromatin at E2F1 DNA-binding site-containing promoters, suppressing E2F1-mediated transcription. The C2 domain of PTEN is required for this suppression. Cancer-associated C2 domain mutations lose the ability to suppress E2F1-mediated transcription. Co-immunoprecipitation, ChIP, promoter reporter assays, deletion/point mutagenesis, nuclear fractionation Cell cycle Medium 29108454
2009 RRP1B is an E2F1-specific transcriptional target that forms a complex with E2F1 on selective proapoptotic target gene promoters (including apoptotic gene promoters). RRP1B is required for E2F1-induced apoptosis in response to DNA-damaging agents. Promoter analysis, ChIP, co-immunoprecipitation, RRP1B knockdown, apoptosis assays The Journal of biological chemistry Medium 20040599
2014 RORα binds to the heptad repeat and marked box region of E2F1, suppresses E2F1-regulated transcription, and inhibits E2F1 acetylation and DNA-binding activity by recruiting HDAC1 to the complex. HDAC1 knockdown or HDAC inhibition partially rescues E2F1 activity repressed by RORα. Co-immunoprecipitation, domain mapping, reporter assays, HDAC1 knockdown, HDAC inhibitor treatment, mammary cell proliferation assays Molecular and cellular biology Medium 24891616
2010 E2F1 activates the p27Kip1 promoter in vivo and induces p27 mRNA and protein expression. E2F1 binds the p27 promoter by ChIP. siRNA depletion of endogenous E2F1 reduces basal p27 levels, and siRNA inhibition of p27 enhances E2F1 transcriptional activity and accelerates cell cycle progression, constituting a negative feedback loop. ChIP, siRNA knockdown, reporter assays, western blot, cell cycle analysis The Journal of biological chemistry Medium 15713665
2005 E2F1 directly regulates DNMT1 expression via conserved E2F binding sites in the DNMT1 promoter. In Rb-/- cells, Dnmt1 transcripts show aberrant cell cycle regulation, leading to aberrant methylation of the Peg3 tumor suppressor locus. Promoter analysis, cell cycle expression profiling in Rb-/- cells, methylation analysis Cancer research Medium 15867357
2010 E2F1 activity antagonizes RB-induced autophagy; RB binding to E2F1 is required for autophagy induction, and downregulation of E2F1 results in high levels of autophagy. Thus, RB induces autophagy by repressing E2F1 activity. RB overexpression, E2F1 knockdown (siRNA), autophagy assays, genetic epistasis with p16INK4a and p27/kip1 Cancer research Medium 20807803
2011 E2F1 induces cell growth and mTORC1 activity in a manner dependent on E2F1's DNA-binding and transcriptional activity. E2F1 induces translocation of mTORC1 to late endosome vesicles in a leucine-dependent mechanism. TSC2 overexpression does not block E2F1-induced mTORC1 activation, indicating the pathway bypasses TSC2/Rheb. E2F1 overexpression with DNA-binding mutant controls, immunolocalization studies, mTORC1 activity assays (S6K phosphorylation), TSC2 epistasis experiments PloS one Medium 21283628
2005 E2F1 promotes apoptosis through the ATM signaling pathway using a mechanism distinct from classical DNA double-strand break induction, as ATM autophosphorylation at Ser1981 is absent but Chk2 Thr68 phosphorylation is ATM-dependent. ATM-deficient and NBS1-mutant primary fibroblasts, phosphorylation assays Molecular cancer research Medium 15190206
2022 In Drosophila, small upstream open reading frames (uORFs) in the 5' UTR of E2f1 mRNA limit E2F1 translation. TOR signaling can bypass uORF-mediated translational repression to promote E2F1 protein synthesis. EGFR signaling also enhances E2F1 translation but through a mechanism less dependent on 5'UTR uORFs. Both pathways regulate cell proliferation via E2F1 protein levels. Transgenic Drosophila with E2f1 5'UTR mutants, genetic epistasis with TOR/EGFR pathway mutants, cell proliferation assays Proceedings of the National Academy of Sciences of the United States of America Medium 35074910
2017 PI3Kδ activation in response to mRNA translation stress (triggered by EBV EBNA1 gly-ala repeat) induces E2F1 mRNA translation. PI3Kδ inhibition with Idelalisib suppresses E2F1 and c-Myc levels and causes cell death in EBNA1-induced B cell lymphomas. PI3Kδ pharmacological inhibition, E2F1 translation assays, B cell lymphoma cell death assays Nature communications Medium 29235459
2006 EGFR co-immunoprecipitates with E2F1 in an EGF-dependent manner. Nuclear EGFR and E2F1 co-occupy the B-Myb promoter in vivo (ChIP). Co-expression of EGFR and E2F1 synergistically activates B-Myb promoter, dependent on both E2F and EGFR binding sites. Co-immunoprecipitation, ChIP, promoter reporter assays with site mutagenesis, co-expression in EGFR-null CHO cells Molecular carcinogenesis Medium 16299810
2005 c-Myc activates transcription of a miRNA cluster (miR-17-5p, miR-20a among others) on human chromosome 13. miR-17-5p and miR-20a negatively regulate E2F1 protein translation, while c-Myc also activates E2F1 transcription—establishing a mechanism where c-Myc simultaneously drives and limits E2F1 expression. Chromatin immunoprecipitation (c-Myc at miRNA locus), miRNA overexpression with E2F1 reporter assays, northern blot Nature High 15944709
2014 E2F1 directly activates transcription of the miR-224/miR-452 cluster through transactivation of the GABRE gene promoter. miR-224/miR-452 targets the metastasis suppressor TXNIP, which provides feedback inhibition of E2F1. This E2F1-miR-224/452-TXNIP axis drives EMT and invasion in melanoma. ChIP, reporter assays, miRNA overexpression/depletion, in vivo lung metastasis assay, TXNIP 3'UTR targeting validation EMBO reports Medium 25341426
2012 E2F1 directly binds the p27 promoter and p53 tumor suppressor interacts with E2F1, and in response to DNA damage, p53-E2F1 complex forms on specific gene promoters to modulate transcriptional outcomes. Co-immunoprecipitation, ChIP The Journal of biological chemistry Low 15713665
2018 E2F1 directly transcriptionally activates AUF1 in HCC (binding to AUF1 promoter), and E2F1 promotes hepatic gluconeogenesis through transcriptional regulation of gluconeogenic genes including Pck1; CDK4-RB1-E2F1 canonical pathway is directly involved. ChIP, E2F1 overexpression/knockout, primary hepatocyte gluconeogenesis assays, diabetic mouse models Molecular metabolism Medium 29526568

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2311 15944709
2000 Regulation of E2F1 activity by acetylation. The EMBO journal 571 10675335
2006 Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nature cell biology 373 16892051
2010 Lysine methylation regulates E2F1-induced cell death. Molecular cell 298 20603083
2008 E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8. Nature 264 18794899
1994 Oncogenic capacity of the E2F1 gene. Proceedings of the National Academy of Sciences of the United States of America 255 7809128
2012 Arginine methylation controls growth regulation by E2F-1. The EMBO journal 184 22327218
2017 E2F1, a Novel Regulator of Metabolism. Frontiers in endocrinology 172 29176962
2002 E2F1 pathways to apoptosis. FEBS letters 161 12354623
2006 Co-regulation of B-Myb expression by E2F1 and EGF receptor. Molecular carcinogenesis 153 16299810
2011 Transcriptional and nontranscriptional functions of E2F1 in response to DNA damage. Cancer research 150 22180494
2005 Regulation of DNA methyltransferase 1 by the pRb/E2F1 pathway. Cancer research 140 15867357
2004 Life and death decisions by E2F-1. Cell death and differentiation 135 14526389
2012 The dark side of E2F1: in transit beyond apoptosis. Cancer research 134 22298593
2011 E2F1 regulates cellular growth by mTORC1 signaling. PloS one 133 21283628
2002 The identification of E2F1-specific target genes. Proceedings of the National Academy of Sciences of the United States of America 129 11904439
2005 Stabilization of E2F1 protein by MDM2 through the E2F1 ubiquitination pathway. Oncogene 123 16170383
2001 E2F-1 induced apoptosis. Apoptosis : an international journal on programmed cell death 121 11388666
2009 The CDK4-pRB-E2F1 pathway controls insulin secretion. Nature cell biology 111 19597485
2004 E2F1 uses the ATM signaling pathway to induce p53 and Chk2 phosphorylation and apoptosis. Molecular cancer research : MCR 111 15140942
2015 E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis. The Journal of clinical investigation 108 26619117
2009 Polycomb protein EZH2 regulates E2F1-dependent apoptosis through epigenetically modulating Bim expression. Cell death and differentiation 106 19893569
2008 The aryl hydrocarbon receptor binds to E2F1 and inhibits E2F1-induced apoptosis. Molecular biology of the cell 104 18524851
2010 The RB-E2F1 pathway regulates autophagy. Cancer research 102 20807803
2009 E2F1 in melanoma progression and metastasis. Journal of the National Cancer Institute 102 20026813
2006 E2F1-induced apoptosis: turning killers into therapeutics. Trends in molecular medicine 100 16530485
2005 E2F1 is crucial for E2F-dependent apoptosis. EMBO reports 100 15976820
2015 POH1 deubiquitylates and stabilizes E2F1 to promote tumour formation. Nature communications 98 26510456
2015 To live or let die - complexity within the E2F1 pathway. Molecular & cellular oncology 97 27308406
2020 A comprehensive review of the roles of E2F1 in colon cancer. American journal of cancer research 84 32266089
1994 Cloning, chromosomal location, and characterization of mouse E2F1. Molecular and cellular biology 84 8114719
2012 E2F1 apoptosis counterattacked: evil strikes back. Trends in molecular medicine 80 23219173
2004 Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice. The Journal of clinical investigation 79 15146237
2014 E2F1 induces miR-224/452 expression to drive EMT through TXNIP downregulation. EMBO reports 75 25341426
2015 E2F1 enhances glycolysis through suppressing Sirt6 transcription in cancer cells. Oncotarget 73 25816777
2005 Activation of p27Kip1 Expression by E2F1. A negative feedback mechanism. The Journal of biological chemistry 71 15713665
2021 Exosomal miRNA-205 promotes breast cancer chemoresistance and tumorigenesis through E2F1. Aging 67 34292880
2003 Evolving intricacies and implications of E2F1 regulation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 67 12665469
2011 PAX8 promotes tumor cell growth by transcriptionally regulating E2F1 and stabilizing RB protein. Oncogene 66 21602887
2016 Citrullination-acetylation interplay guides E2F-1 activity during the inflammatory response. Science advances 65 26989780
2015 Cezanne regulates E2F1-dependent HIF2α expression. Journal of cell science 62 26148512
2002 Differential regulation of E2F1, DP1, and the E2F1/DP1 complex by ARF. Molecular and cellular biology 62 12446760
2015 Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles. Nature cell biology 61 26192440
2009 The E2F family and the role of E2F1 in apoptosis. The international journal of biochemistry & cell biology 60 19539777
2010 Cell proliferation in the absence of E2F1-3. Developmental biology 57 21185283
2021 E2F1: Cause and Consequence of DNA Replication Stress. Frontiers in molecular biosciences 53 33665206
2018 Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4DCAF5 ubiquitin ligase. Nature communications 52 29691401
2018 E2F1 and E2F7 differentially regulate KPNA2 to promote the development of gallbladder cancer. Oncogene 52 30254209
2012 The p38 MAPK-MK2 axis regulates E2F1 and FOXM1 expression after epirubicin treatment. Molecular cancer research : MCR 51 22802261
2022 E2F1-mediated AUF1 upregulation promotes HCC development and enhances drug resistance via stabilization of AKR1B10. Cancer science 49 35178834
2007 E2F1 death pathways as targets for cancer therapy. Journal of cellular and molecular medicine 49 17488475
2010 APC/C(Cdc20) targets E2F1 for degradation in prometaphase. Cell cycle (Georgetown, Tex.) 48 20948288
2017 E2F1 inhibits circulating cholesterol clearance by regulating Pcsk9 expression in the liver. JCI insight 47 28515357
2017 Inhibition of E2F1 activity and cell cycle progression by arsenic via retinoblastoma protein. Cell cycle (Georgetown, Tex.) 45 28880708
2005 Chronic inflammation promotes retinoblastoma protein hyperphosphorylation and E2F1 activation. Cancer research 45 16230367
2017 EGFR Induces E2F1-Mediated Corticotroph Tumorigenesis. Journal of the Endocrine Society 44 29264472
2004 Life, death and E2F: linking proliferation control and DNA damage signaling via E2F1. Cell cycle (Georgetown, Tex.) 43 15190206
2021 CHPF promotes gastric cancer tumorigenesis through the activation of E2F1. Cell death & disease 38 34564711
2014 E2F1 suppresses cardiac neovascularization by down-regulating VEGF and PlGF expression. Cardiovascular research 38 25341896
2010 Transcription factor E2F1 suppresses dendritic cell maturation. Journal of immunology (Baltimore, Md. : 1950) 38 20421650
2016 E2F1: a promising regulator in ovarian carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 26749284
2015 MicroRNA-320 inhibits cell proliferation in glioma by targeting E2F1. Molecular medicine reports 36 25901521
2018 E2F1 inhibition mediates cell death of metastatic melanoma. Cell death & disease 35 29743521
2018 The E2F1-miR-520/372/373-SPOP Axis Modulates Progression of Renal Carcinoma. Cancer research 35 30348808
2013 The E2F1-miRNA cancer progression network. Advances in experimental medicine and biology 35 23377972
2010 Estrogen receptor regulates E2F1 expression to mediate tamoxifen resistance. Molecular cancer research : MCR 35 20215421
2008 E2F1 in gliomas: a paradigm of oncogene addiction. Cancer letters 35 18334281
2006 Implication of the transcription factor E2F-1 in the modulation of neuronal apoptosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 35 17178208
2019 E2f1 deletion attenuates infarct-induced ventricular remodeling without affecting O-GlcNAcylation. Basic research in cardiology 34 31152247
2020 E2F1 Promotes Progression of Bladder Cancer by Modulating RAD54L Involved in Homologous Recombination Repair. International journal of molecular sciences 31 33261027
2018 PTEN Physically Interacts with and Regulates E2F1-mediated Transcription in Lung Cancer. Cell cycle (Georgetown, Tex.) 31 29108454
2015 E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution. Cell death and differentiation 31 25656653
2015 E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells. Cell cycle (Georgetown, Tex.) 31 25892555
2014 E2F1 responds to ultraviolet radiation by directly stimulating DNA repair and suppressing carcinogenesis. Cancer research 31 24741006
1997 Targeting E2F1-DNA complexes with microgonotropen DNA binding agents. Proceedings of the National Academy of Sciences of the United States of America 31 9096302
1994 Interacting domains of E2F1, DP1, and the adenovirus E4 protein. Journal of virology 31 8207796
2014 Tristetraprolin regulates prostate cancer cell growth through suppression of E2F1. Journal of microbiology and biotechnology 30 24150491
2009 Regulation of E2F1-induced apoptosis by the nucleolar protein RRP1B. The Journal of biological chemistry 29 20040599
2024 CircMYBL2 facilitates hepatocellular carcinoma progression by regulating E2F1 expression. Oncology research 28 38827325
2023 LncRNA AGPG Confers Endocrine Resistance in Breast Cancer by Promoting E2F1 Activity. Cancer research 28 37463119
2019 E2F1 mediates the downregulation of POLD1 in replicative senescence. Cellular and molecular life sciences : CMLS 28 30895337
2017 A novel lncRNA, GASL1, inhibits cell proliferation and restricts E2F1 activity. Oncotarget 28 28423601
2017 Regulation of E2F1 Transcription Factor by Ubiquitin Conjugation. International journal of molecular sciences 28 29048367
2013 p53 Suppresses E2F1-dependent PLK1 expression upon DNA damage by forming p53-E2F1-DNA complex. Experimental cell research 28 24076372
2017 PI3Kδ activates E2F1 synthesis in response to mRNA translation stress. Nature communications 27 29235459
2021 Double-targeting CDCA8 and E2F1 inhibits the growth and migration of malignant glioma. Cell death & disease 26 33542211
2018 HMGA1/E2F1 axis and NFkB pathways regulate LPS progression and trabectedin resistance. Oncogene 26 29980789
2010 Ectopic expression of E2F1 stimulates beta-cell proliferation and function. Diabetes 26 20299467
2018 E2F1 promotes hepatic gluconeogenesis and contributes to hyperglycemia during diabetes. Molecular metabolism 25 29526568
2023 Exosomes Derived from E2F1-/- Adipose-Derived Stem Cells Promote Skin Wound Healing via miR-130b-5p/TGFBR3 Axis. International journal of nanomedicine 24 37941530
2022 Translational control of E2f1 regulates the Drosophila cell cycle. Proceedings of the National Academy of Sciences of the United States of America 24 35074910
2020 E2F1 sumoylation as a protective cellular mechanism in oxidative stress response. Proceedings of the National Academy of Sciences of the United States of America 24 32541040
2020 SUMOylation of E2F1 Regulates Expression of EZH2. Cancer research 24 32816857
2021 Up-regulation of MELK by E2F1 promotes the proliferation in cervical cancer cells. International journal of biological sciences 23 34671205
2020 E2F1-activated SPIN1 promotes tumor growth via a MDM2-p21-E2F1 feedback loop in gastric cancer. Molecular oncology 23 32767629
2015 E2F1 controls germ cell apoptosis during the first wave of spermatogenesis. Andrology 23 26311345
2014 RORα binds to E2F1 to inhibit cell proliferation and regulate mammary gland branching morphogenesis. Molecular and cellular biology 22 24891616
1996 Structure and partial genomic sequence of the human E2F1 gene. Gene 22 8964493
1995 Regulation of transcription by E2F1/DP1. Journal of cell science. Supplement 22 8655653
2012 The retinoblastoma protein selectively represses E2F1 targets via a TAAC DNA element during cellular senescence. The Journal of biological chemistry 21 22955272

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