Affinage

E2F3

Transcription factor E2F3 · UniProt O00716

Length
465 aa
Mass
49.2 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

E2F3 is a cell-cycle-regulated transcription factor that functions as a central activator of S-phase gene expression, a repressor of tumor suppressor loci in quiescent cells, and a regulator of centrosome duplication, cardiac development, and neuronal migration. The E2F3 locus encodes two isoforms—growth-regulated E2F3a, whose promoter is induced by Myc at G1/S, and constitutively expressed E2F3b, which forms the predominant Rb-containing repressor complex on targets such as Arf in quiescent cells (PMID:10779352, PMID:15175242). E2F3 directly activates transcription of replication and mitotic genes including Cdc6, cyclin E, cdk2, Aurora-A, and RRM2 through promoter binding, and cooperates with cofactors TFE3 (via its marked box domain), HELLS, and NFY at specific target promoters (PMID:9679057, PMID:12748276, PMID:22157815, PMID:18776222). E2F3 protein stability is regulated by APC/C(Cdh1)-mediated proteasomal degradation at cell cycle exit and by checkpoint kinase phosphorylation in response to DNA damage, while its mRNA is subject to post-transcriptional control by Pumilio/miRNA-mediated translational repression and m6A reader-dependent stabilization (PMID:22580460, PMID:19917728, PMID:22345517, PMID:35266112).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Establishing that E2F3 is the E2F family member whose DNA-binding activity specifically reaccumulates at G1/S resolved which E2F drives the periodic activation of replication genes (Cdc6, cyclin E, cdk2) and showed that E2F3 immunodepletion blocks S-phase entry.

    Evidence Immunodepletion, E2F-specific binding assays, and cell cycle synchronization in mammalian cells

    PMID:9679057

    Open questions at the time
    • Mechanism by which E2F3 is preferentially reactivated at G1/S versus other E2Fs was not defined
    • Full repertoire of direct E2F3 target genes unknown at this stage
  2. 2000 High

    Discovery that the E2F3 locus produces two functionally distinct isoforms—growth-regulated E2F3a and constitutive E2F3b—and that E2F3b forms the predominant Rb complex in quiescent cells established an isoform-based division of labor and explained how promoter architecture (Myc-responsive E-boxes for E2F3a, constitutive elements for E2F3b) generates differential regulation.

    Evidence Novel isoform cloning, co-immunoprecipitation with Rb, promoter dissection and reporter assays

    PMID:10779352 PMID:10779353

    Open questions at the time
    • Whether E2F3a and E2F3b regulate distinct or overlapping target gene sets was not resolved
    • No genome-wide binding data at this point
  3. 2002 High

    In vivo genetic studies revealed that E2F3 loss causes congestive heart failure and impaired cardiac development, and that E2F3 (not E2F1) is the critical mediator of ectopic proliferation in Rb-null tissues, establishing non-redundant developmental roles among activating E2Fs.

    Evidence E2f3 knockout and Rb/E2f compound mutant mice with tissue-specific phenotypic analysis

    PMID:11909960 PMID:12065245

    Open questions at the time
    • Molecular targets of E2F3 in cardiac development not identified
    • Whether E2F3's role in Rb-null proliferation is transcription-dependent was not formally tested
  4. 2003 High

    Two discoveries established unique E2F3 functions: (1) E2F3 interacts specifically with TFE3 through its marked box domain to co-activate p68 DNA polymerase alpha transcription, and (2) E2F3 loss uniquely disrupts centrosome duplication through deregulated cyclin E-dependent kinase activity, linking E2F3 to genomic stability.

    Evidence Co-IP/domain mapping/ChIP for TFE3 interaction; E2f3 KO MEFs with centrosome immunofluorescence and kinase assays

    PMID:12726860 PMID:12748276

    Open questions at the time
    • Whether the centrosome defect is a direct transcriptional consequence of E2F3 target gene deregulation or indirect
    • Other E2F3-specific protein partners at this domain not surveyed
  5. 2004 High

    ChIP and genetic epistasis demonstrated that E2F3b directly occupies and represses the Arf promoter in quiescent cells, and that Arf mutation rescues E2f3-null proliferative defects, establishing the E2F3b–Arf–p53 axis as a key tumor-suppressive circuit.

    Evidence ChIP at Arf promoter, E2f3/Arf double-mutant MEFs, p53/p21 Western blots

    PMID:15175242

    Open questions at the time
    • Whether E2F3b represses Arf through recruitment of a specific corepressor complex was not determined
    • Relevance to in vivo tumorigenesis not yet tested
  6. 2007 High

    E2F3 was found to mediate neuronal migration in a cell-cycle-independent manner downstream of Rb, distinguishing a non-canonical developmental function from its canonical role in proliferation.

    Evidence Rb/E2f3 compound null mice with cortical layering and migration analysis

    PMID:17452454

    Open questions at the time
    • Target genes mediating the migration function are unknown
    • Whether E2F3's migration role requires its transactivation domain was not tested
  7. 2008 High

    Multiple studies expanded E2F3's transcriptional program: E2F3 directly binds and activates the Aurora-A promoter at G2/M; isoform-specific knockouts showed E2F3a (not E2F3b) contributes to proliferation with E2F1 redundancy; and E2F3 loss causes cardiac hypoplasia, confirming its essential role in cardiomyocyte proliferation.

    Evidence ChIP and promoter mutagenesis for Aurora-A; isoform-specific KO mice; cardiac histology and echocardiography in E2f3-null mice

    PMID:18663357 PMID:18776222 PMID:19029823

    Open questions at the time
    • Full G2/M transcriptional program of E2F3 not mapped
    • Mechanism of E2F3's cardiac-specific essentiality versus other tissues unclear
  8. 2009 High

    The discovery that checkpoint kinases phosphorylate E2F3a to stabilize it after DNA damage, and that E2F3 is required for damage-induced apoptosis and E2F1/E2F2 induction, linked E2F3 to the DNA damage response pathway.

    Evidence In vitro kinase assay, phosphorylation site mutagenesis, E2f3-deficient MEFs and mice with apoptosis assays

    PMID:19917728

    Open questions at the time
    • Whether Chk1 or Chk2 is the primary physiological kinase was not resolved
    • Downstream apoptotic effectors controlled by E2F3 in this context not identified
  9. 2011 High

    Identification of the chromatin remodeler HELLS as a genome-wide E2F3 cofactor showed that E2F3-dependent transcription requires an SNF2-like helicase for chromatin access at target promoters.

    Evidence Mass spectrometry, co-IP, ChIP-seq, siRNA knockdown with transcriptome analysis

    PMID:22157815

    Open questions at the time
    • Whether HELLS remodels nucleosomes at E2F3 targets or acts through a different mechanism is unclear
    • Whether HELLS is required at all E2F3 targets or a subset was not resolved
  10. 2012 High

    Two regulatory layers of E2F3 were elucidated: APC/C(Cdh1) targets E2F3 for proteasomal degradation at cell cycle exit, and Pumilio proteins repress E2F3 translation via its 3′ UTR cooperatively with miRNAs—mechanisms subverted in cancer by miRNA loss or UTR shortening.

    Evidence Co-IP of E2F3-Cdh1, proteasome inhibitors, Cdh1 gain/loss-of-function; 3′ UTR reporter assays, Pumilio binding site mapping, Drosophila genetic screen

    PMID:22345517 PMID:22580460

    Open questions at the time
    • Specific degron motifs in E2F3 recognized by Cdh1 not mapped
    • Relative contribution of translational versus post-translational regulation to E2F3 dosage in vivo unknown
  11. 2017 High

    Dosage-dependent gain-of-function of E2F3b (but not E2F3a) was shown to drive spontaneous hepatocellular carcinoma, and E2F3b loss protected against HCC, establishing E2F3b as an isoform-specific oncogene with a distinct chromatin occupancy program in liver.

    Evidence Isoform-specific gain- and loss-of-function alleles in mice, ChIP-seq, transcriptome profiling, spontaneous tumor monitoring

    PMID:28134624

    Open questions at the time
    • Critical E2F3b target genes driving HCC not fully delineated
    • Whether E2F3b's oncogenic role extends to human HCC not directly tested
  12. 2019 High

    E2F3, in complex with TFDP1 and Rb1, was shown to bind allele-specifically to a regulatory element controlling HDAC9 transcription, connecting E2F3 to non-coding variant-mediated gene regulation at a cerebrovascular disease locus.

    Evidence Proteome-wide allele-specific binding, ChIP, 4C chromosome conformation capture, genome editing, gain/loss-of-function

    PMID:31500558

    Open questions at the time
    • Whether E2F3 binding at other disease-associated non-coding variants is widespread
    • Functional consequence of allele-specific HDAC9 regulation for vascular phenotypes not directly shown
  13. 2022 Medium

    Multiple studies established post-transcriptional regulation of E2F3 mRNA by m6A reader proteins: IGF2BP2 (scaffolded by circRNA rtcisE2F) and IGF2BP3 (scaffolded by LINC00958) stabilize E2F3 mRNA, while Smad3 was shown to directly repress E2F3 transcription at its promoter to control β-cell proliferation.

    Evidence RIP, m6A reader pulldown, mRNA stability assays, ChIP of Smad3 at E2F3 promoter, genetic epistasis in islet transplant models

    PMID:34987651 PMID:35266112 PMID:35676262

    Open questions at the time
    • Whether m6A-dependent stabilization of E2F3 mRNA operates in normal (non-cancer) contexts is unknown
    • Relative contributions of transcriptional vs. post-transcriptional control to E2F3 levels in different tissues not quantified
    • Single-lab findings for each mechanism

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: what is the structural basis of E2F3 isoform-specific partner selection, what is the complete set of E2F3b oncogenic targets in hepatocellular carcinoma, and how does E2F3 mediate neuronal migration independently of cell cycle control.
  • No structural model of E2F3 with isoform-specific partners
  • Cell-cycle-independent mechanism in neuronal migration uncharacterized
  • Relative in vivo contributions of protein stability versus mRNA stability regulation to E2F3 dosage undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 6
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1640170 Cell Cycle 6 R-HSA-1266738 Developmental Biology 3 R-HSA-73894 DNA Repair 2 R-HSA-5357801 Programmed Cell Death 1
Partners
CDH1HELLSNFYAPUM1PUM2RB1TFDP1TFE3
Complex memberships
E2F3/DPE2F3b/Rb

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 E2F3 DNA-binding activity specifically reaccumulates at G1/S transitions in proliferating cells (unlike other E2Fs), and immunodepletion of E2F3 activity inhibits S phase induction. E2F3 regulates a cell-cycle-regulated subset of E2F target genes including Cdc6, cyclin E, and cdk2. Immunodepletion, E2F-specific binding assays, cell cycle synchronization, gene expression analysis Genes & development High 9679057
2000 The E2F3 locus encodes two isoforms: E2F3a (growth-regulated, expressed in proliferating cells) and E2F3b (constitutively expressed, transcribed from an intronic promoter). E2F3b specifically associates with Rb in quiescent cells and represents the predominant E2F-Rb complex in quiescent cells, whereas E2F3a is tightly regulated by cell growth. Identification of novel mRNA/protein isoform, co-immunoprecipitation, cell cycle fractionation, promoter mapping Molecular and cellular biology High 10779352
2000 The E2F3a promoter is negatively regulated by E2F binding sites in quiescent cells (similar to E2F1/E2F2) and positively regulated by Myc-binding E-box elements in response to growth stimulation. E2F3b promoter is constitutively active, more similar to E2F4/E2F5 regulation. Promoter deletion analysis, reporter assays, Myc co-transfection Molecular and cellular biology High 10779353
2003 E2F3-specific interaction with the E-box factor TFE3 is mediated by the marked box domain of E2F3 (not E2F1 or E2F2). This interaction synergistically activates transcription of the p68 subunit of DNA polymerase alpha, and both TFE3 and E2F3 are bound to the p68 promoter in vivo. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), reporter assays, domain mapping/mutagenesis Molecular and cellular biology High 12748276
2003 Loss of E2F3 (but not E2F1, E2F2, E2F4, or E2F5) in mouse embryo fibroblasts results in unregulated cyclin E-dependent kinase activity, defects in nucleophosmin B association with centrosomes, premature centriole separation/duplication, centrosome amplification, mitotic spindle defects, and aneuploidy. E2f3 knockout MEFs, kinase assays, centrosome immunofluorescence, comparison with other E2F knockouts Cancer cell High 12726860
2004 E2F3 (predominantly E2F3b in quiescent cells) occupies and represses the Arf tumor suppressor promoter in wild-type MEFs. Loss of E2f3 derepresses Arf, triggering p53 activation and p21Cip1 expression. Arf mutation suppresses p53/p21 induction in E2f3-deficient cells and rescues their cell cycle re-entry defect. Activating E2Fs (E2F1 and E2F3a) are recruited to the Arf promoter in oncogenic conditions. ChIP, genetic epistasis (E2f3/Arf double mutants), MEF proliferation assays, western blot for p53/p21 Genes & development High 15175242
2009 E2F3a is induced by DNA damage through both transcriptional and posttranslational mechanisms. E2F3a is a substrate for checkpoint kinases (Chk kinases) and mutation of the Chk phosphorylation site eliminates DNA damage inducibility. E2F3 is required for DNA damage-induced apoptosis and for transcriptional induction of E2F1 and E2F2 in response to DNA damage. In vitro kinase assay, phosphorylation site mutagenesis, E2f3-deficient MEFs and mice, apoptosis assays Molecular and cellular biology High 19917728
2006 E2F1, E2F2, and E2F3 are required for the negative regulation of the p53-p21CIP1 axis; loss of all three leads to elevated p21CIP1 and G1/S arrest. Inactivation of p21CIP1 restores G1/S entry in E2f1-3 triple-deficient cells, while p53 loss restores both G1/S and G2/M progression and enables oncogenic transformation. Genetic epistasis (E2f1/2/3 triple KO combined with p21 or p53 KO MEFs), cell cycle analysis, transformation assays The Journal of biological chemistry High 17008321
2002 E2F3 loss has the most pronounced effect on reducing ectopic proliferation of fiber cells in Rb-/- lenses; E2F1 is uniquely required for apoptosis in Rb-/- lenses and retinas; E2F3 loss almost completely eliminates ectopic DNA replication and apoptosis in Rb-/- CNS. Compound Rb/E2f mutant mice, in vivo BrdU incorporation, TUNEL apoptosis assay Cell growth & differentiation High 12065245
2002 E2f3 loss causes premature death with congestive heart failure (not tumor formation); E2F1 and E2F3 play critical overlapping roles in development of multiple tissues; tumor suppression is a specific property of E2F1, not E2F3. E2f3 mutant mice, E2f1/E2f3 compound mutant mice, pathological and developmental analysis Molecular and cellular biology High 11909960
2007 Neuronal migration is specifically mediated through E2F3 in a cell-cycle-independent manner; both E2F1 and E2F3 are required for neural precursor proliferation and cell cycle exit, but only E2F3 mediates the Rb requirement for neuronal migration. Rb/E2f1 and Rb/E2f3 compound null mice, BrdU labeling, cortical layering analysis, migration assays Molecular and cellular biology High 17452454
2008 E2F3a and E2f3b make overlapping but different contributions: E2f3a inactivation causes a low-penetrance proliferation defect in vitro; combined E2f3a/E2f1 mutation causes neonatal lethality and cartilage defects; E2f3b loss alone has no detected in vitro or in vivo defect. Isoform-specific E2f3a and E2f3b knockout mice, MEF proliferation assays, developmental phenotype analysis Oncogene High 18663357
2008 E2F3 directly binds to the Aurora-A promoter and transcriptionally activates Aurora-A expression during G2/M. Knockdown of E2F3 decreases Aurora-A mRNA/protein and delays G2/M entry. A region 96 bp upstream of the Aurora-A transcription start site is critical for E2F3-mediated activation. ChIP, promoter deletion/mutation analysis, reporter assay, E2F3 knockdown, cell cycle analysis The Journal of biological chemistry High 18776222
2008 E2F3 is essential for normal cardiac development; E2f3-/- mice show impaired embryonic myocardium proliferation, hypoplastic ventricular walls, septal defects, ultrastructural cardiac muscle defects, and death from congestive heart failure. E2f3 knockout mice, cardiac histology, BrdU proliferation, echocardiography/ultrastructure Cell cycle High 19029823
2011 The SNF2-like helicase HELLS physically interacts with E2F3A in vivo and is required for induction of E2F target genes and cell cycle re-entry. HELLS and E2F3A/B co-occupy gene promoters genome-wide. HELLS depletion severely perturbs E2F3-dependent transcription and growth. Mass spectrometry identification of E2F3B interactors, Co-IP, ChIP-seq, siRNA knockdown, gene expression analysis The EMBO journal High 22157815
2012 APC/C(Cdh1) ubiquitin ligase targets E2F3 for proteasome-dependent degradation during cell cycle exit. E2F3 interacts with Cdh1 but not Cdc20; enforced Cdh1 expression causes proteasome-dependent E2F3 degradation; Cdh1 silencing stabilizes E2F3 in differentiating neuroblastoma cells. Co-immunoprecipitation (E2F3 with Cdh1/Cdc20), proteasome inhibitor experiments, Cdh1 overexpression/siRNA knockdown, western blot Cell cycle High 22580460
2012 Human Pumilio homologs Pum1 and Pum2 repress E2F3 translation by binding to the E2F3 3' UTR and enhance the activity of multiple E2F3-targeting miRNAs. This Pumilio/miRNA-mediated regulation of E2F3 is abrogated in cancer cells by selective miRNA downregulation or 3' UTR shortening. 3' UTR reporter assays, Pumilio binding site mapping, Drosophila genetic screen (suppressor of dE2F1-RNAi), miRNA/Pumilio co-regulation assays Genes & development High 22345517
2013 E2F3 drives postnatal Igf2 down-regulation and E2F3 overexpression causally restores Igf2 expression in late juvenile hepatocytes. E2F3 directly activates mouse Igf2 promoter P2 via E2F binding sites, as shown by reporter assays. ChIP (E2f3 binding to Igf2 promoter), reporter constructs with Igf2 promoter P2 E2F sites, E2f3 gain-of-function in hepatocytes Proceedings of the National Academy of Sciences Medium 23530192
2013 E2F3 mRNA associates with hnRNP-A1 through a conserved binding site in its 3' UTR in BCR/ABL-transformed myeloid cells; BCR/ABL kinase- and hnRNP-A1-dependent upregulation of E2F3 is required for clonogenic activity and leukemogenic potential of BCR/ABL. Ribonomics/RIP (RNA immunoprecipitation), 3' UTR binding site analysis, E2F3 shRNA knockdown, BCR/ABL-transduced E2F3-/- bone marrow cells, in vivo leukemogenesis assay Blood Medium 17925491
2016 ATR-CHK1 signaling stabilizes E2F3 by phosphorylation at S124 in response to MNNG-induced DNA damage. Phosphorylated E2F3 co-transactivates RRM2 (ribonucleotide reductase M2) by directly binding to its promoter together with NFY, which interacts with E2F3 and binds adjacently. ChIP, promoter reporter assays, phosphorylation site analysis, kinase inhibitor experiments, co-IP of E2F3/NFY Biochimica et biophysica acta Medium 26921499
2017 Copy number gains in E2f3b (but not E2f3a) result in dosage-dependent spontaneous hepatocellular carcinoma in mice without involvement of other organs; germ-line loss of E2f3b protects mice against HCC. E2F3B drives a distinct transcriptional program in HCC identified by chromatin occupancy and transcriptome profiling. Gain- and loss-of-function alleles in mice, ChIP-seq, transcriptome profiling, spontaneous tumor analysis The Journal of clinical investigation High 28134624
2019 E2F3 directly binds to the miR-125a promoter (ChIP assay), transcriptionally activating its expression. miR-125a in turn targets DKK3 mRNA 3' UTR, forming an E2F3/miR-125a/DKK3 regulatory axis that promotes gastric cancer metastasis. ChIP assay, dual-luciferase reporter assay, qRT-PCR Cancer cell international Medium 31423109
2019 E2F3/TFDP1/Rb1 complex preferentially binds the common (non-risk) allele of rs2107595 in a regulatory element that interacts with the HDAC9 promoter. E2F3 gain- and loss-of-function demonstrates its key role in mediating allele-specific transcriptional regulation of HDAC9. Proteome-wide allele-specific binding assay, ChIP, chromosome conformation capture (4C), luciferase reporter assay, genome editing, gain- and loss-of-function in cell lines Stroke High 31500558
2021 E2F3 silencing in breast cancer cells reduces tumor growth in vivo by reducing the percentage of cells undergoing mitosis (not S phase); E2F3 modulates expression of EMT-associated genes (Snail, E-cadherin, MMPs) and drives invasion and metastasis. shRNA-mediated E2F3 silencing, in vivo mammary fat pad xenograft assay, mitotic index analysis, Transwell invasion assays Experimental biology and medicine Medium 34365840
2020 lncRNA RBAT1 recruits HNRNPL protein to the E2F3 promoter, thereby activating E2F3 transcription in cis. Demonstrated by ChIRP (chromatin isolation by RNA purification) assays identifying RBAT1-interacting proteins. ChIRP, promoter reporter assay, HNRNPL-E2F3 promoter binding analysis, loss-of-function in vivo Molecular cancer Medium 32669100
2022 rtcisE2F (a read-through circRNA) functions as a scaffold for m6A reader IGF2BP2 and E2F3/E2F6 mRNAs, promoting their association with IGF2BP2 (which inhibits mRNA decay) and inhibiting their association with YTHDF2 (which promotes mRNA decay), thereby stabilizing E2F3 mRNA and promoting liver TIC self-renewal via Wnt/β-catenin. RNA immunoprecipitation (RIP), m6A reader pulldown, mRNA stability assay, loss-of-function experiments in TICs and xenografts Science China. Life sciences Medium 35266112
2022 IGF2BP3 stabilizes E2F3 mRNA in endometrial carcinoma cells by interacting with LINC00958. Silencing LINC00958 partially rescues IGF2BP3-mediated promotion of E2F3 mRNA stability. RIP-seq, RNA pulldown, immunofluorescence-RNA FISH, RNA stability assay, rescue experiments Cell death discovery Medium 35676262
2022 Smad3 binds to the E2F3 promoter and inhibits its transcription, thereby suppressing β cell proliferation. Smad3 knockout upregulates E2F3, promoting G1/S progression in β cells; silencing E2F3 abrogates the proliferative effect of Smad3 KO. ChIP (Smad3 at E2F3 promoter), RNA-seq, Smad3 KO + E2F3 siRNA epistasis, in vivo islet transplant models Theranostics Medium 34987651
2021 E2F3 induces MEX3A transcription; MEX3A in turn activates WNT pathway by suppressing KLF4, retaining cancer cells in undifferentiated/proliferative state. E2F3-MEX3A-KLF4 axis validated by luciferase reporter assays, RNA CLIP, and rescue experiments. CLIP assay, luciferase reporter assay, MEX3A knockout mice, APC-floxed mouse model, rescue experiments Theranostics Medium 36276637
2019 E2F3 binds to the HDAC9 promoter (ChIP confirmed) and, together with Rb1, mediates allele-specific transcriptional repression at the rs2107595 locus. Loss of E2F3 reduces HDAC9 expression in a manner dependent on allelic context. ChIP, gain- and loss-of-function, circularized chromosome conformation capture, genome editing Stroke High 31500558

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Genes & development 323 9679057
2011 MicroRNA-125b suppresses the development of bladder cancer by targeting E2F3. International journal of cancer 165 20549700
2000 Identification of a novel E2F3 product suggests a mechanism for determining specificity of repression by Rb proteins. Molecular and cellular biology 154 10779352
2004 Repression of the Arf tumor suppressor by E2F3 is required for normal cell cycle kinetics. Genes & development 149 15175242
2004 Amplification and overexpression of E2F3 in human bladder cancer. Oncogene 136 14716298
2004 Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome. Oncogene 136 15184867
2012 Pumilio facilitates miRNA regulation of the E2F3 oncogene. Genes & development 127 22345517
2000 Complex transcriptional regulatory mechanisms control expression of the E2F3 locus. Molecular and cellular biology 120 10779353
2010 C/EBPα regulated microRNA-34a targets E2F3 during granulopoiesis and is down-regulated in AML with CEBPA mutations. Blood 112 20889924
2014 miR-200c inhibits invasion, migration and proliferation of bladder cancer cells through down-regulation of BMI-1 and E2F3. Journal of translational medicine 101 25367080
2006 Role of E2F3 expression in modulating cellular proliferation rate in human bladder and prostate cancer cells. Oncogene 100 16909110
2013 Oncogenic ETS fusions deregulate E2F3 target genes in Ewing sarcoma and prostate cancer. Genome research 94 23940108
2012 Anti-oncogenic microRNA-203 induces senescence by targeting E2F3 protein in human melanoma cells. The Journal of biological chemistry 94 22354972
2003 Identification of E-box factor TFE3 as a functional partner for the E2F3 transcription factor. Molecular and cellular biology 89 12748276
2017 Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma. The Journal of clinical investigation 88 28134624
2002 Specificity of E2F1, E2F2, and E2F3 in mediating phenotypes induced by loss of Rb. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 88 12065245
2019 Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma. Cancer cell international 84 31582908
2006 Nuclear overexpression of the E2F3 transcription factor in human lung cancer. Lung cancer (Amsterdam, Netherlands) 77 16938365
2015 miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in gastric cancer cells. Oncotarget 76 25762621
2013 Tumor-suppressive microRNA-449a induces growth arrest and senescence by targeting E2F3 in human lung cancer cells. Cancer letters 76 24211326
2013 MicroRNA-503 inhibits the G1/S transition by downregulating cyclin D3 and E2F3 in hepatocellular carcinoma. Journal of translational medicine 75 23967867
2007 Unique requirement for Rb/E2F3 in neuronal migration: evidence for cell cycle-independent functions. Molecular and cellular biology 74 17452454
2002 Mutant mouse models reveal the relative roles of E2F1 and E2F3 in vivo. Molecular and cellular biology 74 11909960
2014 miR-217 inhibits invasion of hepatocellular carcinoma cells through direct suppression of E2F3. Molecular and cellular biochemistry 72 24671492
2011 The SNF2-like helicase HELLS mediates E2F3-dependent transcription and cellular transformation. The EMBO journal 70 22157815
2007 Inactivation of the Rb pathway and overexpression of both isoforms of E2F3 are obligate events in bladder tumours with 6p22 amplification. Oncogene 70 18037967
2015 MiR-377 targets E2F3 and alters the NF-kB signaling pathway through MAP3K7 in malignant melanoma. Molecular cancer 68 25889255
2015 MicroRNA-449a inhibits proliferation and induces apoptosis by directly repressing E2F3 in gastric cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 67 25871967
2020 A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3. Molecular cancer 64 32669100
2009 E2F3 is a mediator of DNA damage-induced apoptosis. Molecular and cellular biology 64 19917728
2006 Control of the p53-p21CIP1 Axis by E2f1, E2f2, and E2f3 is essential for G1/S progression and cellular transformation. The Journal of biological chemistry 64 17008321
2015 MicroRNA-424 inhibits Akt3/E2F3 axis and tumor growth in hepatocellular carcinoma. Oncotarget 62 26315541
2003 Inactivation of E2F3 results in centrosome amplification. Cancer cell 62 12726860
2014 miR-144 suppresses the proliferation and metastasis of hepatocellular carcinoma by targeting E2F3. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 61 25073510
2020 Circ-RNF111 contributes to paclitaxel resistance in breast cancer by elevating E2F3 expression via miR-140-5p. Thoracic cancer 59 32445273
2018 HOXB9 promotes endometrial cancer progression by targeting E2F3. Cell death & disease 57 29724991
2013 miR-449b inhibits the proliferation of SW1116 colon cancer stem cells through downregulation of CCND1 and E2F3 expression. Oncology reports 57 23674142
2021 Matrix stiffness modulates hepatic stellate cell activation into tumor-promoting myofibroblasts via E2F3-dependent signaling and regulates malignant progression. Cell death & disease 56 34873170
2016 miR128-1 inhibits the growth of glioblastoma multiforme and glioma stem-like cells via targeting BMI1 and E2F3. Oncotarget 54 27705931
2020 Circular RNA (circ-0075804) promotes the proliferation of retinoblastoma via combining heterogeneous nuclear ribonucleoprotein K (HNRNPK) to improve the stability of E2F transcription factor 3 E2F3. Journal of cellular biochemistry 49 32065448
2017 MiRNAs and E2F3: a complex network of reciprocal regulations in human cancers. Oncotarget 49 28947999
2016 MicroRNA-432 functions as a tumor suppressor gene through targeting E2F3 and AXL in lung adenocarcinoma. Oncotarget 47 26942465
2014 Reduced miR-125a-5p expression is associated with gastric carcinogenesis through the targeting of E2F3. Molecular medicine reports 45 25231560
2008 E2f3a and E2f3b make overlapping but different contributions to total E2f3 activity. Oncogene 45 18663357
2017 LF-MF inhibits iron metabolism and suppresses lung cancer through activation of P53-miR-34a-E2F1/E2F3 pathway. Scientific reports 44 28389657
1998 E2F-1 and E2F-3 are functionally distinct in their ability to promote myeloid cell cycle progression and block granulocyte differentiation. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 44 9438389
2013 Evidence that Igf2 down-regulation in postnatal tissues and up-regulation in malignancies is driven by transcription factor E2f3. Proceedings of the National Academy of Sciences of the United States of America 43 23530192
2019 Chromatin remodeler HELLS maintains glioma stem cells through E2F3 and MYC. JCI insight 42 30779712
2019 The Atherosclerosis Risk Variant rs2107595 Mediates Allele-Specific Transcriptional Regulation of HDAC9 via E2F3 and Rb1. Stroke 42 31500558
2008 Identification of Aurora-A as a direct target of E2F3 during G2/M cell cycle progression. The Journal of biological chemistry 42 18776222
2015 MiR-34a Inhibits Viability and Invasion of Human Papillomavirus-Positive Cervical Cancer Cells by Targeting E2F3 and Regulating Survivin. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 41 25675046
2017 MicroRNA-432 targeting E2F3 and P55PIK inhibits myogenesis through PI3K/AKT/mTOR signaling pathway. RNA biology 40 28085550
2017 α-Asarone suppresses the proliferation and migration of ASMCs through targeting the lncRNA-PVT1/miR-203a/E2F3 signal pathway in RSV-infected rats. Acta biochimica et biophysica Sinica 40 28510638
2007 Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis. Blood 38 17925491
2005 HLXB9 activates IL6 in Hodgkin lymphoma cell lines and is regulated by PI3K signalling involving E2F3. Leukemia 38 15772702
2019 MicroRNA-34a suppresses aggressiveness of hepatocellular carcinoma by modulating E2F1, E2F3, and Caspase-3. Cancer management and research 37 31114344
2006 E2F3 is the main target gene of the 6p22 amplicon with high specificity for human bladder cancer. Oncogene 37 16953223
2015 miR-503 inhibits cell proliferation and induces apoptosis in colorectal cancer cells by targeting E2F3. International journal of clinical and experimental pathology 36 26722476
2018 MiR-210 knockdown promotes the development of pancreatic cancer via upregulating E2F3 expression. European review for medical and pharmacological sciences 35 30575904
2020 CircPRMT5 circular RNA promotes proliferation of colorectal cancer through sponging miR-377 to induce E2F3 expression. Journal of cellular and molecular medicine 33 32020730
2007 Selective requirements for E2f3 in the development and tumorigenicity of Rb-deficient chimeric tissues. Molecular and cellular biology 33 17210634
2016 MicroRNA-497 inhibits the proliferation, migration and invasion of human bladder transitional cell carcinoma cells by targeting E2F3. Oncology reports 32 27430325
2015 Silencing of E2F3 suppresses tumor growth of Her2+ breast cancer cells by restricting mitosis. Oncotarget 32 26512919
2015 miR-874 suppresses the proliferation and metastasis of osteosarcoma by targeting E2F3. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 32 26631042
2020 Circular RNA CircPRMT5 Accelerates Proliferation and Invasion of Papillary Thyroid Cancer Through Regulation of miR-30c/E2F3 Axis. Cancer management and research 31 32494192
2014 miR-141 suppresses the growth and metastasis of HCC cells by targeting E2F3. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 31 25142234
2018 Stem-Like Signature Predicting Disease Progression in Early Stage Bladder Cancer. The Role of E2F3 and SOX4. Biomedicines 30 30072631
2022 IGF2BP3 enhances the mRNA stability of E2F3 by interacting with LINC00958 to promote endometrial carcinoma progression. Cell death discovery 29 35676262
2021 m6A-Mediated Upregulation of LINC00857 Promotes Pancreatic Cancer Tumorigenesis by Regulating the miR-150-5p/E2F3 Axis. Frontiers in oncology 29 33680969
2014 Autoregulatory feedback loop of EZH2/miR-200c/E2F3 as a driving force for prostate cancer development. Biochimica et biophysica acta 28 25017995
2022 rtcisE2F promotes the self-renewal and metastasis of liver tumor-initiating cells via N6-methyladenosine-dependent E2F3/E2F6 mRNA stability. Science China. Life sciences 27 35266112
2019 MicroRNA-503 contributes to podocyte injury via targeting E2F3 in diabetic nephropathy. Journal of cellular biochemistry 27 30834596
2019 QKI-6 inhibits bladder cancer malignant behaviours through down-regulating E2F3 and NF-κB signalling. Journal of cellular and molecular medicine 27 31449345
2018 MiR-194-5p inhibits cell migration and invasion in bladder cancer by targeting E2F3. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 26 30570877
2015 miR-34c plays a role of tumor suppressor in HEC‑1-B cells by targeting E2F3 protein. Oncology reports 26 25846116
2008 E2F3 plays an essential role in cardiac development and function. Cell cycle (Georgetown, Tex.) 26 19029823
2022 Identifying the E2F3-MEX3A-KLF4 signaling axis that sustains cancer cells in undifferentiated and proliferative state. Theranostics 25 36276637
2021 E2F3 drives the epithelial-to-mesenchymal transition, cell invasion, and metastasis in breast cancer. Experimental biology and medicine (Maywood, N.J.) 25 34365840
2021 lncRNA SNHG22 sponges miR‑128‑3p to promote the progression of colorectal cancer by upregulating E2F3. International journal of oncology 25 34368861
2021 Long noncoding RNA plasmacytoma variant translocation 1 promotes progression of colorectal cancer by sponging microRNA-152-3p and regulating E2F3/MAPK8 signaling. Cancer science 25 34418232
2019 Knockdown of lncRNA HOXA-AS2 Inhibits Viability, Migration and Invasion of Osteosarcoma Cells by miR-124-3p/E2F3. OncoTargets and therapy 25 31853184
2004 E2F3-a novel repressor of the ARF/p53 pathway. Developmental cell 25 15177020
2022 Smad3 deficiency improves islet-based therapy for diabetes and diabetic kidney injury by promoting β cell proliferation via the E2F3-dependent mechanism. Theranostics 24 34987651
2022 The lncRNA NEAT1/miRNA-766-5p/E2F3 Regulatory Axis Promotes Prostate Cancer Progression. Journal of oncology 24 35237319
2021 Circular RNA CDR1as promotes tumor progression by regulating miR-432-5p/E2F3 axis in pancreatic cancer. Cancer cell international 24 33593338
2020 Loss of lncRNA MIAT ameliorates proliferation and fibrosis of diabetic nephropathy through reducing E2F3 expression. Journal of cellular and molecular medicine 24 33009725
2018 E2F3 promotes cancer growth and is overexpressed through copy number variation in human melanoma. OncoTargets and therapy 24 30214236
2018 HIV-1 Tat protein promotes neuronal dysregulation by inhibiting E2F transcription factor 3 (E2F3). The Journal of biological chemistry 24 30591585
2016 ATR-CHK1-E2F3 signaling transactivates human ribonucleotide reductase small subunit M2 for DNA repair induced by the chemical carcinogen MNNG. Biochimica et biophysica acta 24 26921499
2013 E2f2 induces cone photoreceptor apoptosis independent of E2f1 and E2f3. Cell death and differentiation 24 23558950
2012 APC/C (Cdh1) controls the proteasome-mediated degradation of E2F3 during cell cycle exit. Cell cycle (Georgetown, Tex.) 24 22580460
2019 The E2F3/miR-125a/DKK3 regulatory axis promotes the development and progression of gastric cancer. Cancer cell international 23 31423109
2016 miR‑34a suppresses proliferation and induces apoptosis of human lens epithelial cells by targeting E2F3. Molecular medicine reports 23 27840975
2012 Curtailing overexpression of E2F3 in breast cancer using siRNA (E2F3)-based gene silencing. Archives of medical research 23 22960857
2020 Resveratrol Attenuates High Glucose-Induced Vascular Endothelial Cell Injury by Activating the E2F3 Pathway. BioMed research international 22 32420356
2020 Exosomal-lncRNA DLEU1 Accelerates the Proliferation, Migration, and Invasion of Endometrial Carcinoma Cells by Regulating microRNA-E2F3. OncoTargets and therapy 22 32904666
2019 RNA N6-methyladenosine modification participates in miR-660/E2F3 axis-mediated inhibition of cell proliferation in gastric cancer. Pathology, research and practice 22 30914234
2017 The role of miR-210, E2F3 and ephrin A3 in angiosarcoma cell proliferation. European journal of dermatology : EJD 22 28739548
2020 Hsa_circ_0008934 promotes the proliferation and migration of osteosarcoma cells by targeting miR-145-5p to enhance E2F3 expression. The international journal of biochemistry & cell biology 21 32822848
2017 SNP co-association and network analyses identify E2F3, KDM5A and BACH2 as key regulators of the bovine milk fatty acid profile. Scientific reports 21 29230020