Affinage

E4F1

Transcription factor E4F1 · UniProt Q66K89

Length
784 aa
Mass
83.5 kDa
Annotated
2026-06-09
36 papers in source corpus 25 papers cited in narrative 25 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

E4F1 is a multifunctional GLI-Krüppel zinc-finger transcription factor that controls cell cycle progression, metabolism, and genome stability, and was originally defined as a direct, sequence-specific activator of the adenovirus E4 promoter whose DNA-binding is phosphorylation-dependent and inducible by E1A (PMID:2956091, PMID:2545525, PMID:9121437). The protein exists as a full-length form (p120E4F1) that represses transcription and an E1A-activated N-terminal 50 kDa fragment (p50E4F1) that stimulates it, the latter associating with E1A and basal factors such as TBP through its transcription regulatory region (PMID:9121437, PMID:32535047). Beyond transcription, E4F1 acts as an atypical E3 ubiquitin ligase that oligo-ubiquitylates p53 on hinge-region lysines distinct from Hdm2 sites, retaining p53 on chromatin to drive a cell cycle arrest program rather than apoptosis (PMID:17110336). E4F1 is required for mitotic fidelity in vivo, where its loss causes chromosomal missegregation and embryonic lethality (PMID:15226446). It governs a transcriptional metabolic program by directly binding and activating pyruvate dehydrogenase complex genes (Dlat, Dld, Mpc1, Slc25a19), with loss causing collapsed PDH activity, lactic acidemia, and metabolic stress (PMID:27621446, PMID:27621431); in neurons it co-regulates Dlat and the Elongator subunit Elp3 to couple AcCoA production to wobble-U34 tRNA acetylation and translation fidelity (PMID:39747033). E4F1 is also a master regulator of the ATR/CHK1 DNA-damage axis, directly driving CHEK1 (and the regulators TTI2 and PPP5C) transcription and physically binding CHK1 to protect it from degradation (PMID:25843721, PMID:25843717, PMID:36012478), and it is recruited to double-strand breaks in a PARP-dependent manner to promote end resection and homologous recombination via the chromatin remodeler BRG1/SMARCA4 (PMID:33692124). Through physical interactions with BMI1, RASSF1A, FHL2, and p53, E4F1 integrates these activities into control of stem cell maintenance, hematopoiesis, and tumor cell survival (PMID:14729613, PMID:16882984, PMID:16652157, PMID:21088222, PMID:34857760).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1987 High

    Established that E4F1 is a bona fide sequence-specific transcriptional activator, defining its founding molecular activity by showing its binding sites are required for E4 enhancer-driven transcription.

    Evidence In vitro transcription and DNA footprinting/gel-shift with binding-site mutants on the adenovirus E4 promoter

    PMID:2956091

    Open questions at the time
    • Did not identify the cellular gene targets beyond the viral E4 promoter
    • No structural basis for sequence recognition
  2. 1989 High

    Showed that E4F1 DNA-binding is post-translationally controlled by phosphorylation and identified the factor as a ~50 kDa polypeptide, linking its activity to signaling.

    Evidence Affinity purification with alkaline phosphatase treatment and in vitro DNA-binding reactivation by infected-cell extract

    PMID:2545525

    Open questions at the time
    • Kinase responsible not identified
    • Phosphorylation sites not mapped
  3. 1990 High

    Distinguished E4F1 from ATF in binding specificity and complex stability and tied E4F1 specifically to E1A-dependent trans-activation, clarifying the functional element it controls.

    Evidence Comparative EMSA, site-specific mutagenesis, and cotransfection reporter assays

    PMID:2169022

    Open questions at the time
    • Molecular basis of differential complex stability unresolved
    • Cellular promoters obeying the same code unidentified
  4. 1997 High

    Cloned the full-length 783-aa GLI-Krüppel protein and showed the 50 kDa species is an N-terminal fragment, revealing that full-length p120 represses while the p50 fragment activates, and that E1A differentially regulates the two forms.

    Evidence Expression cloning, immunological characterization, DNA-binding and reporter assays with phosphorylation analysis

    PMID:9121437

    Open questions at the time
    • Mechanism generating the p50 fragment in cells not defined
    • Domain map of repression vs activation incomplete
  5. 2004 High

    Demonstrated an essential in vivo cell-cycle function: E4F1 is required for mitotic progression and chromosome segregation, with spindle localization, moving it from a viral cofactor to a core cell-cycle regulator.

    Evidence Knockout mouse with blastocyst analysis, spindle immunofluorescence, and flow cytometry

    PMID:15226446

    Open questions at the time
    • Molecular targets driving the mitotic defect not identified
    • Whether spindle localization reflects a non-transcriptional role unresolved
  6. 2004 High

    Identified RASSF1A as a physical partner that cooperates with E4F1 to enforce G1/S arrest, placing E4F1 in a tumor-suppressor interaction network.

    Evidence Yeast two-hybrid, reciprocal pull-down and Co-IP, siRNA, and cell-cycle flow cytometry

    PMID:14729613

    Open questions at the time
    • Mechanistic consequence of the complex on E4F1 targets unclear
    • Interaction domains not mapped
  7. 2006 High

    Revealed an enzymatic activity beyond transcription: E4F1 oligo-ubiquitylates p53 at hinge lysines distinct from Hdm2, channeling p53 toward chromatin-associated arrest rather than apoptosis.

    Evidence In vitro ubiquitylation, MS site mapping, ChIP, and apoptosis-versus-arrest cell-fate readouts

    PMID:17110336

    Open questions at the time
    • The E2 enzyme and full ligase complex not defined
    • How ubiquitylation directs p53 to specific gene programs unresolved
  8. 2006 High

    Placed E4F1 in the BMI1 axis controlling hematopoietic proliferation independent of INK4A/ARF and p53, showing E4f1 knockdown rescues Bmi1-deficient stem cells.

    Evidence Co-IP, RNAi, and hematopoietic transplantation/clonogenic assays

    PMID:16882984

    Open questions at the time
    • The p53/INK4A-independent effector pathway not identified
    • Direct genomic targets in hematopoietic cells unmapped
  9. 2006 High

    Identified FHL2 as a nuclear inhibitor of full-length E4F1 that dampens its antiproliferative and repressive activity and reduces E4F1-p53 complexes in response to UV.

    Evidence In vitro binding, reciprocal Co-IP, immunofluorescence, and repression reporter assays

    PMID:16652157

    Open questions at the time
    • Whether FHL2 affects E4F1 ligase activity not tested
    • Physiological signals beyond UV not explored
  10. 2007 Medium

    Showed E4F1 acts as a corepressor partner of LANP/INHAT, with ataxin-1 competing for LANP to relieve repression, linking E4F1 to chromatin-based repression machinery.

    Evidence Co-IP, competition binding, and transcriptional reporter assays

    PMID:17557114

    Open questions at the time
    • Endogenous target genes of the LANP-E4F1 complex not defined
    • Single-lab finding without independent reconstitution
  11. 2010 High

    Established E4F1 as essential for epidermal stem cell maintenance and positioned it upstream of the BMI1-Arf-p53 pathway in skin homeostasis.

    Evidence Conditional skin knockout, ex vivo clonogenic assays, and genetic epistasis rescues

    PMID:21088222

    Open questions at the time
    • Direct transcriptional targets in stem cells not identified
    • Mechanism linking E4F1 to the BMI1-Arf-p53 axis unresolved at the gene level
  12. 2011 High

    Revealed a selective dependency of transformed cells on E4F1: its loss triggers mitochondrial dysfunction, ROS, and autophagic death in tumor cells but not normal macrophages, with tumor regression in vivo.

    Evidence Conditional deletion in a mouse tumor model, ROS and mitochondrial assays, and shRNA in human lines

    PMID:21708927

    Open questions at the time
    • The transcriptional targets producing the mitochondrial defect not yet defined here
    • Basis of tumor-selective dependence unclear
  13. 2013 Medium

    Extended the tumor-selective dependency to HBV-positive hepatocellular carcinoma via an E4F1-HBx interaction, with E4F1 loss causing autophagy, mitochondrial defects, and G1 arrest in an HBV/p53-dependent manner.

    Evidence Co-precipitation, RNAi, cell-cycle and autophagy assays in HCC lines

    PMID:24163401

    Open questions at the time
    • Functional consequence of the HBx interaction on E4F1 activity not defined
    • Single-lab, context-restricted finding
  14. 2015 High

    Connected E4F1 to the DNA-damage checkpoint by both directly transcribing Chek1 and protecting CHK1 protein from degradation, with Chek1 re-expression fully rescuing E4f1-loss phenotypes.

    Evidence ChIP-seq, conditional knockout, Co-IP, DNA-damage/cell-cycle assays, and Chek1 overexpression rescue (two independent labs)

    PMID:25843717 PMID:25843721

    Open questions at the time
    • Mechanism by which E4F1 stabilizes CHK1 protein not defined
    • Coupling between the checkpoint and metabolic roles unresolved
  15. 2016 High

    Defined E4F1 as a direct transcriptional controller of the pyruvate-oxidation program (Dlat, Dld, Mpc1, Slc25a19), establishing its central role in metabolic gene regulation with in vivo PDH and endurance phenotypes.

    Evidence ChIP, muscle- and keratinocyte-specific knockouts, PDH activity and metabolic flux assays, shRNA of Dlat, and dietary/pharmacological rescue

    PMID:27621431 PMID:27621446

    Open questions at the time
    • How metabolic and checkpoint target programs are co-selected unresolved
    • Upstream signals tuning this program not identified
  16. 2021 High

    Showed E4F1 is recruited to double-strand breaks in a PARP-dependent manner and promotes end resection and homologous recombination through BRG1/SMARCA4, adding a direct chromatin-level repair function.

    Evidence Live-cell imaging of recruitment, PARP inhibition, Co-IP with BRG1, and HR/resection assays

    PMID:33692124

    Open questions at the time
    • Whether transcriptional and recruitment roles act in parallel at breaks unresolved
    • Residues mediating PARP-dependent recruitment not mapped
  17. 2021 High

    Demonstrated direct E4F1-p53 co-occupancy at the SCD1 locus controlling monounsaturated fatty acid synthesis in adipose tissue, broadening the metabolic program to lipid metabolism with p53-dependent rescue.

    Evidence ChIP co-occupancy, Co-IP, adipose-specific knockout, metabolic phenotyping, and p53-deletion/oleate rescue

    PMID:34857760

    Open questions at the time
    • Whether E4F1 ubiquitylation of p53 contributes at this locus untested
    • Tissue specificity of the SCD1 program unexplained
  18. 2022 High

    Generalized the ATR/CHK1 axis control to human TNBC, showing E4F1 directly regulates CHEK1, TTI2, and PPP5C and that its loss collapses ATM/ATR/CHK1 signaling and sensitizes cells to DNA-damaging agents.

    Evidence ChIP-seq, RNA-seq, E4F1 depletion, signaling assays, PDX ChIP validation, and drug-sensitivity assays

    PMID:36012478

    Open questions at the time
    • Single-lab finding
    • Relative contribution of each target to checkpoint failure not dissected
  19. 2023 Medium

    Identified E4F1 as a mutation-specific activator of the -57A>C TERT promoter, implicating it in telomerase reactivation in cancer.

    Evidence SILAC pull-down proteomics screen, ChIP, TERT reporter, and telomerase activity assays

    PMID:37918959

    Open questions at the time
    • Why E4F1 selectively binds the mutant promoter not defined
    • Single-lab proteomics-based discovery
  20. 2024 Medium

    Showed E4F1 cooperates with NF-κB/RelA to control dynamic miR-210 expression during TLR immune responses, extending its transcriptional partnerships to innate immunity.

    Evidence RelA-E4F1 Co-IP, reporter assays, and miR-210 expression upon TLR stimulation with knockdowns

    PMID:38742642

    Open questions at the time
    • Direct binding of E4F1 at the miR-210 locus in human cells not fully resolved
    • Physiological immune consequence untested
  21. 2025 High

    Revealed that E4F1 coordinates AcCoA production (via Dlat/PDC) with its utilization by the Elongator subunit Elp3 for wobble-U34 tRNA acetylation, linking metabolism to translation fidelity and neuronal survival.

    Evidence Conditional knockout, ChIP at Dlat and Elp3, tRNA acetylation and translation-fidelity assays, and PDH-deficient patient cell analysis

    PMID:39747033

    Open questions at the time
    • How E4F1 simultaneously sets producer and consumer gene levels mechanistically unresolved
    • Generality of the PDC-Elongator crosstalk beyond neurons untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how E4F1 integrates its dual roles as a transcription factor and an atypical p53 E3 ligase, and what signals partition it between metabolic, checkpoint, and DNA-repair programs in a given cell type.
  • No structural model coordinating DNA-binding and ligase domains
  • Mechanism stabilizing CHK1 protein undefined
  • Rules selecting metabolic vs checkpoint target genes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3 GO:0003723 RNA binding 1 GO:0016874 ligase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005694 chromosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1430728 Metabolism 4 R-HSA-1640170 Cell Cycle 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-73894 DNA Repair 2 R-HSA-392499 Metabolism of proteins 1
Partners
BMI1CHEK1FHL2RASSF1ARELASMARCA4TP53

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 E4F1 (E4F) binds to two sites within the adenovirus E4 enhancer and one site upstream of the E4 TATA box, and this binding is required for constitutive enhancer-driven transcriptional activity in vitro, establishing E4F1 as a direct transcriptional activator of the E4 promoter. In vitro transcription assay, DNA binding (footprinting/gel shift), mutational analysis of binding sites The EMBO journal High 2956091
1989 E4F (E4F1) DNA-binding activity is regulated by phosphorylation: alkaline phosphatase treatment abolishes binding activity, and re-incubation with extract from virus-infected cells restores it. A 50 kDa polypeptide was identified as the E4F factor by affinity purification. Affinity purification, alkaline phosphatase treatment, in vitro DNA-binding assay Genes & development High 2545525
1990 E4F and ATF recognize the same DNA element in the E4 promoter but differ in sequence specificity (E4F binds only a subset of ATF sites, not E2/E3 promoter ATF sites) and complex stability (E4F forms a stable complex; ATF dissociates rapidly). Only E4F-binding sequences confer E1A inducibility, linking E4F specifically to E1A-dependent trans-activation. DNA-binding assays (EMSA), cotransfection reporter assays, site-specific mutagenesis Molecular and cellular biology High 2169022
1992 E1A-dependent activation of the E4 promoter in HeLa cells is primarily mediated through E4F (not ATF-2): carboxy-terminal auxiliary regions (AR1, AR2) of E1A 289R are required for E1A-induced activation of E4F DNA-binding activity but not ATF-2 activity. Cotransfection reporter assays, E1A deletion mutant analysis The EMBO journal Medium 1387083
1997 E4F1 (50 kDa E4F) is the N-terminal fragment of the full-length 783-amino-acid protein (human homolog of murine phiAP3), a GLI-Krüppel zinc-finger protein. E1A(13S) differentially phosphorylates and regulates both forms: it stimulates DNA-binding of the 50 kDa fragment while reducing that of the full-length protein. The full-length protein represses the E4 promoter in the absence of E1A, while the fragment stimulates it in E1A's presence. Expression cloning, immunological characterization, DNA-binding assays, transient transfection reporter assays, phosphorylation analysis Molecular and cellular biology High 9121437
2004 E4F1 is required for mitotic progression during embryonic cell cycles: E4F knockout mice die at peri-implantation, and E4F−/− blastocysts show chromosomal missegregation, defects in mitotic progression, and increased apoptosis. E4F localizes to the mitotic spindle during M phase in early embryos. Gene targeting (knockout mouse), live-cell imaging/immunofluorescence of spindle localization, flow cytometry for cell cycle analysis Molecular and cellular biology High 15226446
2004 E4F1 (p120 E4F) physically interacts with RASSF1A in yeast and mammalian cells, forming a complex in vivo, confirmed by in vitro pull-down, in vivo pull-down, and co-immunoprecipitation. RASSF1A knockdown disrupts this interaction. Co-expression of RASSF1A and p120(E4F) enhances G1 arrest and S-phase inhibition. Yeast two-hybrid, in vitro pull-down, in vivo pull-down, co-immunoprecipitation, siRNA knockdown, flow cytometry (cell cycle) Cancer research High 14729613
2006 E4F1 is an atypical E3 ubiquitin ligase for p53 that stimulates oligo-ubiquitylation on lysine residues in the hinge region of p53, distinct from Hdm2 target lysines. E4F1-dependent ubiquitylated p53 remains chromatin-associated and promotes a p53-dependent transcriptional program for cell cycle arrest rather than apoptosis. E4F1 and PCAF mediate mutually exclusive post-translational modifications of p53. In vitro ubiquitylation assay, mass spectrometry (site mapping), chromatin immunoprecipitation (ChIP), reporter assays, cell fate (apoptosis vs. growth arrest) analysis Cell High 17110336
2006 E4F1 interacts with BMI1 in hematopoietic cells (co-immunoprecipitation/pulldown), and genetic interaction between Bmi1 and E4f1 regulates cellular proliferation. RNAi-mediated knockdown of E4f1 rescues clonogenic and repopulating ability of Bmi1−/− hematopoietic cells, and this interaction is independent of INK4A/ARF and p53. Co-immunoprecipitation, RNA interference, hematopoietic transplantation assays, clonogenic assays Genes & development High 16882984
2006 Full-length E4F1 (p120E4F1), but not its truncated E1A-activated form (p50E4F1), directly interacts with the LIM-only protein FHL2 in vitro and in vivo in the nuclear compartment. This interaction inhibits E4F1's antiproliferative activity and its transcriptional repression, and reduces nuclear E4F1-p53 complexes. FHL2 nuclear accumulation upon UV light promotes endogenous E4F1-FHL2 complex formation. In vitro binding assay, co-immunoprecipitation, immunofluorescence (localization), reporter assays, UV-light stimulation Oncogene High 16652157
2007 E4F1 forms a complex with LANP (an INHAT corepressor) and modulates transcriptional repression. Ataxin 1 competes with E4F1 for LANP binding, thereby relieving the transcriptional repression induced by the LANP-E4F1 complex. Co-immunoprecipitation, transcriptional reporter assays, competition binding assays EMBO reports Medium 17557114
2010 E4F1 is essential for epidermal stem cell (ESC) maintenance and skin homeostasis in vivo. E4F1 conditional knockout in skin causes ESC pool exhaustion. Clonogenic potential of E4F1 KO ESCs is rescued by BMI1 overexpression or by Ink4a/Arf or p53 depletion, placing E4F1 upstream of the BMI1-Arf-p53 pathway in skin stem cells. Conditional knockout (Cre-loxP), ex vivo clonogenic assays, genetic epistasis (double knockout/overexpression rescue) PNAS High 21088222
2011 E4F1 inactivation in myeloid leukemic (histiocytic sarcoma) cells causes mitochondrial defects, increased reactive oxygen species (ROS) production, and massive autophagic cell death — effects observed in transformed cells but not normal primary macrophages. In vivo, genetic ablation of E4F1 in established tumors causes tumor regression. Cre-mediated conditional deletion in vivo (genetically engineered mouse model), ROS measurement, mitochondrial function assays, autophagy markers, shRNA knockdown in human cell lines The Journal of experimental medicine High 21708927
2013 E4F1 physically interacts with hepatitis B virus protein HBx (co-precipitation in HCC cell lines). E4F1 depletion in HBV-expressing (but not HBV-negative) HCC cells induces hepatocyte vacuolation, increased autophagy, mitochondrial defects, and G1 cell cycle arrest; these effects are partially prevented by siRNA against HBx or p53. Co-immunoprecipitation/co-precipitation, RNA interference, flow cytometry (cell cycle), autophagy assays, metabolic profiling Carcinogenesis Medium 24163401
2015 E4F1 directly controls transcription of Chek1 (CHK1) and genes involved in mitochondrial function. E4F1 inactivation in p53-deficient transformed cells causes CHK1-dependent checkpoint deficiency combined with mitochondrial dysfunction (increased ROS, energy stress, inhibition of de novo pyrimidine synthesis), leading to cell death. E4F1 ChIP-seq identified direct genomic targets in MEFs. ChIP-seq, RNA-seq (differential expression in E4F1 KO vs. WT), conditional knockout, ROS/metabolic assays, cell death assays Cell reports High 25843721
2015 E4F1 physically interacts with CHK1 protein and protects it from degradation, functioning as a master regulator of CHK1. E4f1-deficient hematopoietic cells accumulate DNA damage, show S-phase and mitotic progression defects, and undergo apoptosis; ectopic Chek1 expression fully rescues these defects. Co-immunoprecipitation, conditional knockout (Cre-loxP in hematopoietic cells), DNA damage assays, cell cycle analysis, Chek1 overexpression rescue Cell reports High 25843717
2016 E4F1 transcriptionally regulates four genes (Dlat, Dld, Mpc1, Slc25a19) required for pyruvate oxidation; E4F1 dysfunction results in ~80% decrease in pyruvate dehydrogenase (PDH) complex activity and altered pyruvate metabolism. Muscle-specific E4f1 knockout mice show low PDH activity, severe endurance defects, and chronic lactic acidemia. ChIP (direct binding to target gene promoters), conditional knockout (muscle-specific), PDH activity assay, metabolic profiling, pharmacological PDH stimulation and ketogenic diet rescue PNAS High 27621431 27621446
2016 In keratinocytes, E4F1 transcriptionally regulates Dlat (encoding the E2 subunit of the PDH complex); E4f1 KO keratinocytes show impaired PDH activity, redirected glycolytic flux toward lactate, extracellular matrix remodeling, and loss of clonogenic potential. shRNA depletion of Dlat alone recapitulates these defects. Conditional knockout, PDH activity assay, metabolic flux assay (lactate measurement), shRNA knockdown, clonogenic assay PNAS High 27621431
2020 The 50 kDa form of E4F1 (p50E4F1) stably associates with E1A289R in vivo via the p50E4F1 transcription regulatory (TR) region and E1A CR3. E1A-mediated trans-activation requires the p50E4F1 TR region to be promoter-bound and depends on E1A CR3, CR1, and N-terminal domains. Multiple cellular proteins including TBP bind the p50E4F1 TR region in vitro. In vivo co-immunoprecipitation, in vitro binding assays, GAL4-fusion trans-activation assays, deletion mutagenesis Gene Medium 32535047
2021 E4F1 promotes DNA double-strand break (DSB) repair by: (1) being recruited to DNA breaks in a PARP-dependent manner; (2) promoting ATR/CHK1 signaling and DNA-end resection for homologous recombination; (3) binding to the chromatin remodeler BRG1/SMARCA4 and together with PARP-1 mediating BRG1 recruitment to DNA lesions. Live-cell imaging (recruitment to DNA breaks), PARP inhibitor treatment, co-immunoprecipitation (E4F1-BRG1), HR repair assays, DNA resection assays, CHK1 signaling assays PNAS High 33692124
2021 E4F1 directly interacts with p53 and both co-occupy the Stearoyl-CoA Desaturase-1 (SCD1) locus in adipocytes to regulate monounsaturated fatty acid synthesis. E4F1 deficiency in adipose tissue activates a p53-dependent transcriptional program controlling lipid metabolism; p53 inactivation or oleate supplementation partially restores adiposity in E4F1-deficient mice. ChIP (E4F1 and p53 co-occupancy at SCD1 locus), co-immunoprecipitation (E4F1-p53 interaction), conditional adipose-specific knockout, metabolic phenotyping, genetic epistasis (p53 inactivation rescue) Nature communications High 34857760
2022 In triple-negative breast cancer (TNBC) cells, E4F1 directly binds and regulates CHEK1 and two additional post-transcriptional regulators of the ATM/ATR-CHK1 axis: TTI2 (TTT complex, required for ATM/ATR folding/stability) and PPP5C (phosphatase regulating ATM/ATR signaling). E4F1 depletion downregulates CHK1, ATM, and ATR protein levels and signaling, causing failure to arrest in S-phase upon Gemcitabine treatment and sensitization to DNA-damaging agents. ChIP-seq, RNA-seq, E4F1 depletion (shRNA/siRNA), ATM/ATR/CHK1 signaling assays, PDX ChIP validation, drug sensitivity assays International journal of molecular sciences High 36012478
2023 E4F1 binds specifically to the -57A>C mutant TERT promoter and activates TERT transcription and telomerase activity. ZNF148 binds the wild-type TERT promoter and is a separate activating factor. Both were identified by a systematic proteomics screen (SILAC-based pull-down) and validated by ChIP in corresponding cell lines. SILAC-based proteomics pull-down screen, ChIP, TERT reporter assay, telomerase activity assay Genome research Medium 37918959
2024 In human cells, NF-κB/RelA cooperates with E4F1 to regulate dynamic expression of hsa-miR-210 during TLR immune responses, mirroring a conserved mechanism where Dorsal cooperates with Su(Hw) in Drosophila. Co-immunoprecipitation (RelA-E4F1), reporter assays, miR-210 expression assays upon TLR stimulation, knockdown experiments Nucleic acids research Medium 38742642
2025 E4F1 directly transcriptionally regulates both Dlat (PDH complex E2 subunit) and Elp3 (catalytic subunit of the Elongator complex) in neurons, coordinating AcCoA production by PDC and its utilization by Elongator to acetylate tRNAs at wobble uridine 34 (U34). This E4F1-mediated coordination ensures translation fidelity and neuronal cell survival during brain development. PDH-deficient (Leigh syndrome) cells show a perturbed PDC-to-ELP3 crosstalk. Conditional knockout (mouse), ChIP (direct promoter binding), primary neuronal cell assays, tRNA acetylation assay, translation fidelity assay, PDH-deficient patient cell analysis Nature communications High 39747033

Source papers

Stage 0 corpus · 36 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1987 A cellular transcription factor E4F1 interacts with an E1a-inducible enhancer and mediates constitutive enhancer function in vitro. The EMBO journal 184 2956091
2006 E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation. Cell 181 17110336
1989 DNA-binding activity of the adenovirus-induced E4F transcription factor is regulated by phosphorylation. Genes & development 100 2545525
2022 m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency. Clinical and translational medicine 62 35340126
2004 Identification of the E1A-regulated transcription factor p120 E4F as an interacting partner of the RASSF1A candidate tumor suppressor gene. Cancer research 62 14729613
2004 The E4F protein is required for mitotic progression during embryonic cell cycles. Molecular and cellular biology 49 15226446
2006 E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells. Genes & development 47 16882984
1990 E4F and ATF, two transcription factors that recognize the same site, can be distinguished both physically and functionally: a role for E4F in E1A trans activation. Molecular and cellular biology 40 2169022
2015 The transcription factor E4F1 coordinates CHK1-dependent checkpoint and mitochondrial functions. Cell reports 39 25843721
2007 The role of LANP and ataxin 1 in E4F-mediated transcriptional repression. EMBO reports 38 17557114
2006 The LIM-only protein FHL2 is a negative regulator of E4F1. Oncogene 37 16652157
2016 E4F1 controls a transcriptional program essential for pyruvate dehydrogenase activity. Proceedings of the National Academy of Sciences of the United States of America 35 27621446
2010 Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis. Proceedings of the National Academy of Sciences of the United States of America 35 21088222
1997 The adenovirus E1A-regulated transcription factor E4F is generated from the human homolog of nuclear factor phiAP3. Molecular and cellular biology 33 9121437
2021 Zinc finger protein E4F1 cooperates with PARP-1 and BRG1 to promote DNA double-strand break repair. Proceedings of the National Academy of Sciences of the United States of America 32 33692124
2016 E4F1-mediated control of pyruvate dehydrogenase activity is essential for skin homeostasis. Proceedings of the National Academy of Sciences of the United States of America 30 27621431
1992 The carboxy-terminal exon of the adenovirus E1A protein is required for E4F-dependent transcription activation. The EMBO journal 29 1387083
1991 E1A-mediated activation of the adenovirus E4 promoter can occur independently of the cellular transcription factor E4F. Molecular and cellular biology 22 1831536
2015 E4F1 is a master regulator of CHK1-mediated functions. Cell reports 21 25843717
2011 E4F1 deficiency results in oxidative stress-mediated cell death of leukemic cells. The Journal of experimental medicine 21 21708927
2021 The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes. Nature communications 16 34857760
2019 MicroRNA-33-3p Regulates Vein Endothelial Cell Apoptosis in Selenium-Deficient Broilers by Targeting E4F1. Oxidative medicine and cellular longevity 16 31249647
2023 Transcription factor E4F1 dictates spermatogonial stem cell fate decisions by regulating mitochondrial functions and cell cycle progression. Cell & bioscience 11 37749649
2020 E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice. Animals : an open access journal from MDPI 10 32962114
2015 Description of an optimized ChIP-seq analysis pipeline dedicated to genome wide identification of E4F1 binding sites in primary and transformed MEFs. Genomics data 10 26484288
2013 Downregulation of transcription factor E4F1 in hepatocarcinoma cells: HBV-dependent effects on autophagy, proliferation and metabolism. Carcinogenesis 10 24163401
2011 E4F1 dysfunction results in autophagic cell death in myeloid leukemic cells. Autophagy 10 22024746
2024 NF-κB factors cooperate with Su(Hw)/E4F1 to balance Drosophila/human immune responses via modulating dynamic expression of miR-210. Nucleic acids research 9 38742642
2021 Angiotensin II promotes EMT of hepatocellular carcinoma cells through high mobility group protein B1 mediated by E4F1. Biochemical and biophysical research communications 8 33618227
2018 E4F1 silencing inhibits the cell growth through cell-cycle arrest in malignant transformed cells induced by hydroquinone. Journal of biochemical and molecular toxicology 7 30506647
2023 Transcription factor E4F1 as a regulator of cell life and disease progression. Science advances 6 37774036
2022 Multi-Level Control of the ATM/ATR-CHK1 Axis by the Transcription Factor E4F1 in Triple-Negative Breast Cancer. International journal of molecular sciences 5 36012478
2023 E4F1 and ZNF148 are transcriptional activators of the -57A > C and wild-type TERT promoter. Genome research 3 37918959
2025 E4F1 coordinates pyruvate metabolism and the activity of the elongator complex to ensure translation fidelity during brain development. Nature communications 1 39747033
2026 The transcription factor E4F1 is crucial for spermatogonial differentiation and meiosis progression in mice. BMC genomics 0 41981464
2020 Multiple domains in the 50 kDa form of E4F1 regulate promoter-specific repression and E1A trans-activation. Gene 0 32535047

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