Affinage

E2F3

Transcription factor E2F3 · UniProt O00716

Length
465 aa
Mass
49.2 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

E2F3 is a cell-cycle-regulated transcription factor that drives the G1/S transition and DNA synthesis by activating rate-limiting replication and proliferation genes, including Cdc6, cyclin E, Cdk2, B-myb, cyclin A, and cdc2 (PMID:9679057, PMID:10733529). The E2F3 locus produces two transcription-factor isoforms: E2F3a, tightly induced at G1/S and positively regulated by Myc through E-box elements in its promoter, and E2F3b, generated from an alternative ACG translational start at codon 102, constitutively expressed and associated with Rb in quiescence (PMID:10779353, PMID:10918599). Beyond S-phase control, E2F3a directly binds the Aurora-A promoter to drive G2/M gene expression and mitotic progression (PMID:18776222, PMID:26512919). E2F3 operates downstream of pRb—Rb loss releases E2F3-driven proliferation, and E2F3 is the principal E2F activator for ectopic proliferation and apoptosis in Rb-null tissues (PMID:12065245, PMID:16909110, PMID:17452454)—and upstream of a p53/p21 negative-feedback loop that restrains E2F activator output (PMID:17167174). It also couples to DNA damage signaling as a direct checkpoint-kinase (Chk) substrate stabilized after damage and is required for damage-induced apoptosis (PMID:19917728). E2F3 activity is constrained at multiple levels: APC/C(Cdh1)-mediated proteasomal degradation during cell cycle exit (PMID:22580460) and Pumilio (Pum1/Pum2)/miRNA-mediated translational repression via its 3' UTR (PMID:22345517). The chromatin remodeler HELLS physically interacts with E2F3 and co-occupies E2F3 target promoters genome-wide to enable target induction and cell-cycle re-entry (PMID:22157815). E2F3 is activated in human cancer through 6p22 amplification driving overexpression of both isoforms in bladder cancer (PMID:14716298, PMID:18037967), and it cooperates with oncogenic ETS fusions (EWSR1/FLI1, TMPRSS2/ERG) that co-regulate E2F3 target gene networks (PMID:23940108). Distinct isoforms carry out non-canonical roles: the outer-mitochondrial-membrane isoform E2F3d mediates hypoxia-induced mitophagy via an LC3-interacting region (PMID:30740539), while E2F3 also controls cell-cycle-independent neuronal migration downstream of Rb (PMID:17452454). E2F3 has additional in vivo roles in cardiac development, endothelial/ischemic angiogenesis, and tumor-associated macrophage migration programs (PMID:19029823, PMID:23603666, PMID:26549026).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1998 High

    Established that E2F3 is functionally required for S-phase entry in cycling cells rather than merely a passenger DNA-binding activity, anchoring its role in proliferation control.

    Evidence Immunodepletion of E2F3 from extracts and E2F DNA-binding/gene expression assays across the cell cycle

    PMID:9679057

    Open questions at the time
    • Did not resolve which E2F3 isoform carries the activity
    • Direct promoter occupancy of named targets not yet shown
  2. 2000 High

    Defined the dual-isoform architecture of the locus and how E2F3a is transcriptionally controlled, distinguishing a growth-regulated from a constitutive product.

    Evidence Genomic/promoter-reporter analysis of two transcription start sites; in vitro translation and ACG-codon mutagenesis identifying E2F3b; Rb co-IP

    PMID:10779353 PMID:10918599

    Open questions at the time
    • Distinct in vivo functions of E2F3a vs E2F3b not yet separated
    • Did not address post-translational regulation
  3. 2000 High

    Genetic loss-of-function showed E2F3 is specifically and non-redundantly required for mitogen-induced activation of E2F target genes and DNA synthesis.

    Evidence E2f3-knockout MEFs with gene expression, BrdU and proliferation assays; lack of rescue by E2F1

    PMID:10733529

    Open questions at the time
    • Mechanism of E2F3 specificity over E2F1 unresolved
    • Direct vs indirect target regulation not distinguished
  4. 2002 High

    Placed E2F3 epistatically downstream of pRb and revealed tissue-specific functional dominance among E2F activators.

    Evidence Compound Rb/E2F null mouse genetics with histology, BrdU and TUNEL across lens and CNS

    PMID:12065245

    Open questions at the time
    • Molecular basis of tissue specificity unknown
    • Did not separate cell-cycle from non-cell-cycle effects
  5. 2006 High

    Demonstrated that E2F3-driven proliferation in cancer cells is pRb-status dependent and identified novel E2F3 targets.

    Evidence siRNA knockdown and ectopic expression in bladder/prostate cancer cells; microarray profiling; pRB depletion

    PMID:16909110

    Open questions at the time
    • Direct vs indirect status of new targets (PLK1, caveolin-2) not all validated by ChIP
    • Isoform contributions not separated
  6. 2007 High

    Resolved the p53/p21 negative-feedback loop that restrains E2F activator output, linking E2F3 activity to checkpoint control.

    Evidence Conditional E2f1/2/3 triple knockout plus p53 knockout in MEFs; CDK activity and Rb phosphorylation assays

    PMID:17167174

    Open questions at the time
    • E2F3-specific (vs E2F1/2) contribution to the loop not isolated
    • Direct activator of p53/p21 induction unidentified
  7. 2007 High

    Uncovered a cell-cycle-independent function for E2F3 in neuronal migration and confirmed isoform-required proliferation in amplified human tumors.

    Evidence Compound Rb/E2F3 null mice with migration assays; isoform-specific shRNA in bladder tumors with array-CGH

    PMID:17452454 PMID:18037967

    Open questions at the time
    • Migration-relevant E2F3 transcriptional targets not defined
    • Mechanism linking 6p22 amplification to both isoforms unresolved
  8. 2008 High

    Identified direct G2/M target regulation and clarified largely overlapping in vivo roles of the two isoforms plus a developmental requirement.

    Evidence ChIP and promoter mutation analysis of Aurora-A; isoform-specific knockout mice; E2f3-null cardiac histology and EM

    PMID:18663357 PMID:18776222 PMID:19029823

    Open questions at the time
    • Why E2F3a/E2F3b are largely interchangeable in most tissues unexplained
    • Direct cardiac transcriptional targets not mapped
  9. 2009 High

    Connected E2F3 to DNA-damage signaling as a direct Chk-kinase substrate required for damage-induced apoptosis.

    Evidence In vitro Chk kinase assays, phosphosite mutagenesis, E2f3-knockout cells/mice and apoptosis assays

    PMID:19917728

    Open questions at the time
    • Which Chk kinase predominates in vivo not pinned down
    • Structural consequence of phosphorylation on E2F3 stability not detailed
  10. 2011 High

    Defined two layers of negative regulation—translational repression via Pumilio/miRNA and chromatin cooperation via HELLS—that tune E2F3 activity and target induction.

    Evidence 3' UTR binding/translational reporters and miRNA assays for Pum1/2; mass spec, reciprocal ChIP-seq and knockdown for HELLS

    PMID:22157815 PMID:22345517

    Open questions at the time
    • Quantitative contribution of Pumilio vs miRNA repression unresolved
    • Whether HELLS is recruited by E2F3 or vice versa not fully defined
  11. 2012 High

    Showed APC/C(Cdh1) targets E2F3 for proteasomal degradation, providing the post-translational off-switch during cell cycle exit.

    Evidence Co-IP with Cdh1/Cdc20, gain- and loss-of-function with proteasome inhibitors in differentiating neuroblastoma

    PMID:22580460

    Open questions at the time
    • Degron sequence on E2F3 not mapped
    • Isoform selectivity of degradation untested
  12. 2013 High

    Demonstrated tissue-level roles of E2F3 in endothelial proliferation/angiogenesis and convergence of oncogenic ETS fusions on E2F3 target networks.

    Evidence Endothelial-specific E2f3 knockout in hind-limb ischemia; genome-wide ChIP-seq/transcriptomics with promoter mutation for EWSR1/FLI1 and TMPRSS2/ERG

    PMID:23603666 PMID:23940108

    Open questions at the time
    • Direct physical interaction between ETS fusions and E2F3 not established
    • Endothelial E2F3 target program incompletely defined
  13. 2015 High

    Distinguished isoform- and context-specific oncogenic roles: a mitotic-progression function in breast cancer and an E2f3b-driven migration program in tumor-associated macrophages.

    Evidence shRNA knockdown with mitotic index/Nek2 rescue in Her2+ cells; macrophage-specific conditional E2f3 knockout in PyMT model with metastasis quantification

    PMID:26512919 PMID:26549026

    Open questions at the time
    • Mechanistic basis for E2f3b enrichment in TAMs unknown
    • Direct mitotic-gene targets in breast cancer not all mapped
  14. 2017 High

    Genetically isolated E2f3b as the dosage-dependent driver of spontaneous hepatocellular carcinoma, separating isoform tumorigenic functions in vivo.

    Evidence Allelic series of E2f3a/E2f3b loss- and gain-of-function in mice with spontaneous tumor endpoints, ChIP and transcriptomics

    PMID:28134624

    Open questions at the time
    • Mechanism of E2f3b-specific oncogenic program unresolved
    • Whether human HCC depends on the same isoform not addressed
  15. 2019 High

    Identified the mitochondrial isoform E2F3d as a mediator of hypoxia-induced mitophagy and characterized a genetic-risk-variant enhancer mechanism for E2F3 transcriptional repression.

    Evidence Novel isoform identification with fractionation/IF, LC3-interaction and mitophagy assays for E2F3d; allele-specific binding proteomics, ChIP, 4C and CRISPR editing at rs2107595/HDAC9

    PMID:30740539 PMID:31500558

    Open questions at the time
    • How a single locus generates transcription-factor and mitochondrial isoforms not fully resolved
    • In vivo relevance of E2F3d mitophagy unaddressed
  16. 2019 Medium

    Extended E2F3's regulatory reach to neuronal CREB control, miRNA-axis oncogenic programs, and glioblastoma stem-cell cooperation with HELLS/MYC.

    Evidence ChIP/reporter assays for CREB and miR-125a promoters; miR-34a/E2F3 rescue in neurons; co-IP of HELLS with E2F3/MYC and knockdown in GSCs

    PMID:30591585 PMID:30779712 PMID:31423109

    Open questions at the time
    • Single-lab single-study findings for several axes
    • Direct vs indirect target regulation not uniformly validated
  17. 2022 Medium

    Mapped upstream regulators (Smad3 repression, lncRNA/IGF2BP3 mRNA stabilization, RBAT1/HNRNPL cis-activation) and downstream metastatic/EMT programs that set E2F3 levels and outputs in disease.

    Evidence ChIP for Smad3-E2F3 promoter and E2F3-FGF2 promoter; ChIRP, RIP-seq and RNA-stability assays; siRNA/knockout with EMT and metastasis readouts

    PMID:32669100 PMID:34365840 PMID:34873170 PMID:34987651 PMID:35676262

    Open questions at the time
    • Most are single-lab studies in specific cancer contexts
    • Generality of these regulatory axes across tissues untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single E2F3 locus partitions transcriptional (E2F3a/b) and mitochondrial (E2F3d) isoform functions, and what determines isoform-specific oncogenic versus tumor-suppressive outcomes, remains unresolved.
  • No unified model linking isoform generation to context-specific function
  • Structural basis of E2F3 target selectivity vs other activator E2Fs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-73894 DNA Repair 1 R-HSA-9612973 Autophagy 1
Partners
CDH1HELLSMYCPUM1PUM2RB1TFDP1
Complex memberships
E2F3/TFDP1/Rb1 complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 E2F3-binding activity specifically reaccumulates at G1/S transitions during cycling (not just the initial G1 after growth stimulation), and immunodepletion of E2F3 activity inhibits S phase induction in proliferating cells. E2F3 controls expression of rate-limiting DNA replication initiation genes including Cdc6, cyclin E, and Cdk2. Immunodepletion of E2F3 from cell extracts; E2F DNA-binding activity assays; gene expression analysis across cell cycle Genes & development High 9679057
2000 The E2F3 locus encodes two protein products: E2F3a (tightly regulated by cell growth, expressed at G1/S) and E2F3b (constitutively expressed throughout the cell cycle). The E2F3a promoter is negatively regulated by E2F binding sites in quiescent cells and positively regulated by Myc via E-box elements upon growth stimulation, similar to E2F1 and E2F2 promoters. Genomic sequence analysis; promoter-reporter assays; characterization of two distinct transcription start sites; cell cycle expression analysis Molecular and cellular biology High 10779353
2000 E2F3-deficient mouse embryonic fibroblasts show dramatically impaired mitogen-induced transcriptional activation of E2F-responsive genes (B-myb, cyclin A, cdc2, cdc6, DHFR) that are not rescued by E2F1, establishing E2F3 as specifically required for transcriptional activation controlling G1/S transition rate and DNA synthesis rate. E2f3 knockout mouse-derived MEFs; gene expression analysis; BrdU incorporation; proliferation assays Genes & development High 10733529
2000 E2F3b is produced from the E2F3 mRNA via an alternative translational start site at codon 102 (an ACG codon), lacking 101 N-terminal amino acids relative to full-length E2F3. E2F3b is expressed throughout the cell cycle with peak levels in G0 where it associates with Rb. Transfection and in vitro translation; mutagenesis of the ACG codon at position 102; co-immunoprecipitation with Rb Oncogene High 10918599
2002 In Rb-deficient mice, E2F3 makes the most pronounced contribution to ectopic proliferation of lens fiber cells among E2F1/2/3. In the CNS, loss of E2F1 or E2F3 can almost completely eliminate ectopic DNA replication and apoptosis in Rb-null embryos, establishing functional specificity and epistatic relationship of E2F3 downstream of Rb. Compound null mouse genetics (Rb/E2F double knockouts); histological analysis; BrdU incorporation; TUNEL assay Cell growth & differentiation High 12065245
2004 E2F3 gene amplification at 6p22 is associated with overexpression of E2F3 mRNA and high nuclear E2F3 protein in bladder cancer, establishing DNA amplification as a mechanism of E2F3 activation in human cancer. FISH for gene amplification; RT-PCR for mRNA; immunohistochemistry for protein in primary tumors Oncogene Medium 14716298
2006 siRNA knockdown of E2F3 in bladder cancer cells with 6p22 amplification strongly reduces BrdU incorporation and proliferation rate. E2F3 knockdown reduces expression of known targets (Cyclin A, CDC2) and novel targets (PLK1, caveolin-2). Ectopic E2F3a enhances BrdU incorporation in pRB-null prostate cancer cells but not in pRB-positive cells, and pRB depletion restores E2F3a-driven proliferation in pRB-positive cells. siRNA knockdown; BrdU incorporation; cDNA microarray expression profiling; ectopic overexpression; pRB depletion Oncogene High 16909110
2007 In bladder tumors with 6p22.3 amplification, both E2F3a and E2F3b isoforms are overexpressed and individually required for proliferation; knockdown of either isoform alone has antiproliferative effects, with maximal effect when both are knocked down together. E2F3 overexpression co-occurs with loss of Rb pathway function (RB1 loss or CDKN2A deletion) in these tumors. shRNA-mediated knockdown of E2F3a or E2F3b separately or together; proliferation assays; array-CGH; Rb expression analysis in primary bladder tumors Oncogene High 18037967
2007 E2F1 and E2F3 are both required for Rb-dependent control of neural precursor proliferation, cell cycle exit, and laminar patterning. Neuronal migration is specifically mediated through E2F3 in a cell cycle-independent manner, as established by compound Rb/E2F3 null mice but not Rb/E2F1 null mice. Compound null mouse genetics (Rb/E2F3 double knockout); histological analysis; BrdU incorporation; neuronal migration assays Molecular and cellular biology High 17452454
2007 Conditional triple knockout of E2f1, E2f2, and E2f3 in MEFs activates p53 and induces p21(CIP1), which inhibits CDK activity and Rb phosphorylation, leading to Rb/E2F-mediated repression of E2F target genes and proliferation block. Inactivation of p53 in these cells restores CDK activity, Rb phosphorylation, and E2F target expression, revealing a p53-dependent negative feedback loop controlled by E2F activators. Conditional gene targeting (triple E2f1/2/3 knockout); p53 conditional knockout; gene expression analysis; CDK activity assays; Rb phosphorylation assays Molecular and cellular biology High 17167174
2008 E2F3a is a direct transcriptional activator of Aurora-A (AURKA): E2F3 binds directly to the Aurora-A promoter at a region 96 bp upstream of the transcription initiation site, stimulates promoter activity, and controls Aurora-A mRNA expression during G2/M. E2F3 knockdown decreases Aurora-A mRNA and protein and delays G2/M entry. Chromatin immunoprecipitation (ChIP); promoter-reporter assays; deletion and mutation analysis of Aurora-A promoter; ectopic E2F3 expression; stable E2F3 knockdown; cell cycle analysis The Journal of biological chemistry High 18776222
2008 E2f3a and E2f3b have largely overlapping functions in vivo. E2f3a-specific knockout causes a low-penetrance proliferation defect in vitro; E2f3b knockout alone has no proliferation effect. Combined E2f3a/E2f1 mutation causes neonatal lethality and cartilage defects, indicating E2f3a can substitute for E2f1 in most tissues. E2f3a-specific and E2f3b-specific knockout mice; compound E2f3a/E2f1 double knockout; proliferation assays in MEFs; developmental phenotype analysis Oncogene High 18663357
2008 E2F3 is essential for normal cardiac development: E2f3-null mice display impaired embryonic myocardial proliferation, hypoplastic ventricular walls, and atrial/ventricular septal defects, with surviving animals dying of congestive heart failure with ultrastructural cardiac defects. E2f3 knockout mice; histological analysis of cardiac development; electron microscopy for ultrastructural analysis Cell cycle High 19029823
2009 E2F3a is induced by DNA damage through both transcriptional and post-translational mechanisms. E2F3a is a direct substrate of checkpoint kinases (Chk kinases), and mutation of the Chk phosphorylation site eliminates its DNA damage inducibility. E2f3 is required for DNA damage-induced apoptosis in vivo, and E2F1/E2F2 transcriptional induction by DNA damage is E2f3-dependent. DNA damage treatment assays; in vitro kinase assays with Chk kinases; phosphorylation site mutagenesis; E2f3 knockout cells and mice; apoptosis assays Molecular and cellular biology High 19917728
2011 Human Pumilio homologs Pum1 and Pum2 repress E2F3 translation by binding to the E2F3 3' UTR and also enhance the activity of multiple E2F3-targeting miRNAs. In cancer cells, this regulation is circumvented by selective miRNA downregulation or 3' UTR shortening that removes Pumilio regulatory elements. RNA binding assays (3' UTR binding); translational reporter assays; miRNA functional assays; Drosophila genetic screen; 3' UTR mapping Genes & development High 22345517
2011 The SNF2-like helicase HELLS physically interacts with E2F3A in vivo, co-localizes at E2F3 target gene promoters genome-wide (ChIP-seq), and is required for induction of E2F target genes and cell cycle re-entry. HELLS cooperates with E2F3's oncogenic functions in tumor cell proliferation. Mass spectrometric identification of E2F3B interaction partners; co-immunoprecipitation; ChIP-seq for HELLS and E2F3A/B genome-wide; HELLS knockdown; cell cycle re-entry assays 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 of E2F3 with Cdh1 and Cdc20; overexpression of Cdh1/Cdc20 with proteasome inhibitor treatment; siRNA knockdown of Cdh1; cell cycle exit assays Cell cycle High 22580460
2013 EWSR1/FLI1 (Ewing sarcoma) and TMPRSS2/ERG (prostate cancer) ETS fusion oncoproteins synergistically co-regulate a large fraction of E2F3 target genes, as demonstrated by integrated genome-wide DNA binding and transcription analyses with promoter activity and mutation analyses. ChIP-seq for EWSR1/FLI1 and E2F3 genome-wide; transcriptome profiling; promoter activity assays; mutation analyses of E2F-ETS composite elements Genome research High 23940108
2015 E2f3 specifically controls a gene expression program in tumor-associated macrophages (TAMs) associated with cytoskeleton rearrangements, cell migration, and adhesion—but not TAM proliferation or survival. Specific ablation of E2f3 in TAMs (not tumor epithelial cells) attenuates lung metastasis in the PyMT breast cancer model. E2f3b (not E2f3a) isoform is elevated in TAMs. Cell type-specific conditional E2f3 knockout in macrophages (PyMT model); histological analysis; gene expression profiling; lung metastasis quantification Oncogene High 26549026
2017 Copy number gains in E2f3b (but not E2f3a alone) cause dosage-dependent spontaneous hepatocellular carcinoma in mice. Conversely, germ-line loss of E2f3b, but not E2f3a, protects against HCC. ChIP and transcriptome profiling identified an E2F3B-driven transcriptional program associated with HCC development. Series of loss- and gain-of-function alleles in mice; spontaneous tumor monitoring; ChIP for chromatin occupancy; transcriptome profiling The Journal of clinical investigation High 28134624
2019 E2F3d, a previously unidentified E2F3 isoform, localizes to the outer mitochondrial membrane and mediates hypoxia-induced mitophagy in cancer cells. E2F3d contains an LC3-interacting region (LIR) motif in its cytosolic domain; its overexpression induces mitochondrial fragmentation and mitophagy; depletion of E2F3s attenuates hypoxia-induced mitophagy and increases reactive oxygen species. Identification of novel isoform; subcellular fractionation and immunofluorescence for mitochondrial localization; LC3 interaction assay; mitophagy assays; ROS measurement; overexpression and knockdown Communications biology High 30740539
2019 E2F3 binds the CREB promoter (validated by ChIP and transient transfection) and activates CREB expression; HIV-1 Tat protein suppresses E2F3 via upregulation of miR-34a, causing neuronal dysfunction including neurite retraction. E2F3 overexpression or miR-34a inhibition neutralizes Tat's effects and restores synaptophysin distribution. ChIP for E2F3 binding to CREB promoter; luciferase reporter assay; miR-34a overexpression/inhibition; E2F3 overexpression; synaptophysin imaging in murine neurons The Journal of biological chemistry Medium 30591585
2019 HELLS (chromatin remodeler) interacts with E2F3 and MYC in glioblastoma stem cells (GSCs) to regulate gene expression critical to GSC proliferation and maintenance; HELLS depletion disrupts GSC proliferation, survival, and self-renewal with replication stress and DNA damage induction. Co-immunoprecipitation of HELLS with E2F3 and MYC; HELLS knockdown with proliferation/survival/self-renewal phenotype assays; gene expression correlation analysis; in vivo mouse tumor models JCI insight Medium 30779712
2019 E2F3 transcriptionally activates miR-125a by binding to its promoter (established by ChIP assay), creating an E2F3/miR-125a/DKK3 regulatory axis in gastric cancer where E2F3 promotes metastasis by inducing miR-125a which suppresses DKK3. ChIP assay for E2F3 binding to miR-125a promoter; dual luciferase reporter assay for miR-125a/DKK3 interaction; overexpression and knockdown functional assays; wound healing and Transwell assays Cancer cell international Medium 31423109
2019 The atherosclerosis risk variant rs2107595 disrupts an E2F3 consensus binding site; the E2F3/TFDP1/Rb1 complex preferentially binds the common allele. E2F3 binding to this enhancer region loops to the HDAC9 promoter and represses HDAC9 expression; the risk allele abolishes E2F3 binding, increasing HDAC9 transcriptional activity. Proteome-wide allele-specific nuclear binding (mass spec); ChIP for E2F3 and Rb1 at rs2107595; circularized chromosome conformation capture (4C); CRISPR genome editing; luciferase reporter assay; gain/loss-of-function in cell lines Stroke High 31500558
2020 RBAT1 lncRNA recruits HNRNPL protein to the E2F3 promoter, thereby activating E2F3 transcription in cis (cis-activation mechanism established by ChIRP identifying RBAT1-interacting proteins and promoter occupancy assays). Chromatin isolation by RNA purification (ChIRP) to identify RBAT1-interacting proteins; RBAT1 knockdown with E2F3 expression readout; functional tumor assays in vitro and in vivo Molecular cancer Medium 32669100
2021 E2F3 controls a CD36-AKT-E2F3 mechanosignaling cascade in hepatic stellate cells (HSCs) activated by matrix stiffness. ChIP-qPCR confirmed that E2F3 directly binds the FGF2 promoter; stiffness promotes FGF2 expression downstream of E2F3, and conditional E2F3 knockout in mice reduces HSC activation and HCC progression. ChIP-qPCR for E2F3 binding to FGF2 promoter; shRNA-mediated E2F3 knockdown; AKT inhibitors; CD36 shRNA; conditional E2F3 knockout mice; in vivo HCC models Cell death & disease Medium 34873170
2021 E2F3 silencing in breast cancer cells reduces cell invasion, migration, and tumor metastasis in vivo, and modulates expression of EMT-associated genes (Snail, E-cadherin, MMPs), and regulates Shugoshin-1 expression, placing E2F3 upstream of EMT transcriptional programs. E2F3 siRNA knockdown in TNBC cell lines; invasion/migration assays; in vivo tumor growth and metastasis in NSG mice; gene expression analysis of EMT markers Experimental biology and medicine Medium 34365840
2022 IGF2BP3 stabilizes E2F3 mRNA by interacting with LINC00958 lncRNA in the cytoplasm of endometrial carcinoma cells; LINC00958 knockdown reduces IGF2BP3-mediated E2F3 mRNA stability; RIP-seq and RNA pulldown confirmed the LINC00958-IGF2BP3 interaction, and RNA stability assays confirmed the downstream effect on E2F3. RIP-seq; RNA pulldown; RNA stability assays; immunofluorescence-FISH; RNA-seq for downstream targets; loss-of-function rescue experiments Cell death discovery Medium 35676262
2022 Smad3 binds to the E2F3 promoter and inhibits E2F3 transcription; Smad3 deficiency upregulates E2F3, promoting β cell proliferation via G1/S entry; silencing E2F3 abrogates the proliferative effect of Smad3 knockout, establishing a Smad3-E2F3 axis in β cell cycle control. ChIP for Smad3 binding to E2F3 promoter; RNA-seq in Smad3KO vs WT islets; E2F3 siRNA in Smad3KO β cells; Smad3 knockout mice; islet transplantation models Theranostics Medium 34987651
2013 E2F3 (endothelial-specific) promotes endothelial cell proliferation and ischemic angiogenesis: endothelial-specific E2F3 knockout mice show significantly reduced capillary density, endothelial proliferation, and G1/S gene expression after hind-limb ischemia, with necrosis development. Endothelial-specific conditional E2F3 knockout mice; hind-limb ischemia model; Laser-Doppler perfusion; capillary density measurement; BrdU incorporation in isolated ECs Journal of molecular and cellular cardiology High 23603666
2015 E2F3 silencing in Her2+ breast cancer cells reduces tumor growth in vivo by reducing the percentage of mitotic cells without affecting S phase entry, demonstrating a specific role for E2F3 in mitotic progression. Nek2 overexpression rescued centrosome amplification caused by E2F3 silencing. shRNA knockdown of E2F3 in HCC1954 cells; in vivo mammary fat pad tumor growth; mitotic index measurement; S phase measurement; Nek2 overexpression rescue Oncotarget Medium 26512919

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 326 9679057
2016 Long non-coding RNA NEAT1 promotes non-small cell lung cancer progression through regulation of miR-377-3p-E2F3 pathway. Oncotarget 282 27351135
2000 E2f3 is critical for normal cellular proliferation. Genes & development 262 10733529
2011 MicroRNA-125b suppresses the development of bladder cancer by targeting E2F3. International journal of cancer 165 20549700
2004 Amplification and overexpression of E2F3 in human bladder cancer. Oncogene 137 14716298
2004 Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome. Oncogene 136 15184867
2004 E2F3 amplification and overexpression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer. Oncogene 129 15122326
2012 Pumilio facilitates miRNA regulation of the E2F3 oncogene. Genes & development 128 22345517
2000 Complex transcriptional regulatory mechanisms control expression of the E2F3 locus. Molecular and cellular biology 123 10779353
2018 Circular RNA hsa_circ_0008039 promotes breast cancer cell proliferation and migration by regulating miR-432-5p/E2F3 axis. Biochemical and biophysical research communications 112 29807010
2008 The E2F3-Oncomir-1 axis is activated in Wilms' tumor. Cancer research 103 18519660
2014 miR-200c inhibits invasion, migration and proliferation of bladder cancer cells through down-regulation of BMI-1 and E2F3. Journal of translational medicine 102 25367080
2006 Role of E2F3 expression in modulating cellular proliferation rate in human bladder and prostate cancer cells. Oncogene 100 16909110
2018 Long non-coding RNA H19 promotes glucose metabolism and cell growth in malignant melanoma via miR-106a-5p/E2F3 axis. Journal of cancer research and clinical oncology 96 29350287
2013 Oncogenic ETS fusions deregulate E2F3 target genes in Ewing sarcoma and prostate cancer. Genome research 95 23940108
2005 Gains and overexpression identify DEK and E2F3 as targets of chromosome 6p gains in retinoblastoma. Oncogene 94 16007192
2017 Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma. The Journal of clinical investigation 89 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
2007 E2f1, E2f2, and E2f3 control E2F target expression and cellular proliferation via a p53-dependent negative feedback loop. Molecular and cellular biology 85 17167174
2019 Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma. Cancer cell international 84 31582908
2012 A unilateral negative feedback loop between miR-200 microRNAs and Sox2/E2F3 controls neural progenitor cell-cycle exit and differentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience 83 22993445
2015 miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in gastric cancer cells. Oncotarget 77 25762621
2006 Nuclear overexpression of the E2F3 transcription factor in human lung cancer. Lung cancer (Amsterdam, Netherlands) 77 16938365
2019 lncRNA NEAT1 facilitates melanoma cell proliferation, migration, and invasion via regulating miR-495-3p and E2F3. Journal of cellular physiology 76 31173352
2007 Unique requirement for Rb/E2F3 in neuronal migration: evidence for cell cycle-independent functions. Molecular and cellular biology 74 17452454
2005 Divergent siblings: E2F2 and E2F4 but not E2F1 and E2F3 induce DNA synthesis in cardiomyocytes without activation of apoptosis. Circulation research 73 15718499
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
2000 Identification of E2F-3B, an alternative form of E2F-3 lacking a conserved N-terminal region. Oncogene 69 10918599
2015 MiR-377 targets E2F3 and alters the NF-kB signaling pathway through MAP3K7 in malignant melanoma. Molecular cancer 68 25889255
2015 MiR-141 Inhibits Gastric Cancer Proliferation by Interacting with Long Noncoding RNA MEG3 and Down-Regulating E2F3 Expression. Digestive diseases and sciences 67 26233544
2020 A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3. Molecular cancer 66 32669100
2009 E2F3 is a mediator of DNA damage-induced apoptosis. Molecular and cellular biology 65 19917728
2015 MicroRNA-424 inhibits Akt3/E2F3 axis and tumor growth in hepatocellular carcinoma. Oncotarget 62 26315541
2020 Circ-RNF111 contributes to paclitaxel resistance in breast cancer by elevating E2F3 expression via miR-140-5p. Thoracic cancer 59 32445273
2018 Long non-coding RNA TTN-AS1 promotes cell growth and metastasis in cervical cancer via miR-573/E2F3. Biochemical and biophysical research communications 59 30135013
2021 Matrix stiffness modulates hepatic stellate cell activation into tumor-promoting myofibroblasts via E2F3-dependent signaling and regulates malignant progression. Cell death & disease 57 34873170
2018 HOXB9 promotes endometrial cancer progression by targeting E2F3. Cell death & disease 57 29724991
2017 Long non-coding RNA NEAT1 regulates E2F3 expression by competitively binding to miR-377 in non-small cell lung cancer. Oncology letters 55 29085511
2016 miR128-1 inhibits the growth of glioblastoma multiforme and glioma stem-like cells via targeting BMI1 and E2F3. Oncotarget 54 27705931
2017 MiRNAs and E2F3: a complex network of reciprocal regulations in human cancers. Oncotarget 49 28947999
2015 E2f3 in tumor macrophages promotes lung metastasis. Oncogene 49 26549026
2016 MicroRNA-432 functions as a tumor suppressor gene through targeting E2F3 and AXL in lung adenocarcinoma. Oncotarget 47 26942465
2008 E2f3a and E2f3b make overlapping but different contributions to total E2f3 activity. Oncogene 46 18663357
2017 LF-MF inhibits iron metabolism and suppresses lung cancer through activation of P53-miR-34a-E2F1/E2F3 pathway. Scientific reports 44 28389657
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
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
2018 MiR-210 knockdown promotes the development of pancreatic cancer via upregulating E2F3 expression. European review for medical and pharmacological sciences 36 30575904
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
2019 miR‑145 suppresses ovarian cancer progression via modulation of cell growth and invasion by targeting CCND2 and E2F3. Molecular medicine reports 34 30864742
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
2020 Circular RNA CircPRMT5 Accelerates Proliferation and Invasion of Papillary Thyroid Cancer Through Regulation of miR-30c/E2F3 Axis. Cancer management and research 32 32494192
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
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
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 28 35266112
2014 Autoregulatory feedback loop of EZH2/miR-200c/E2F3 as a driving force for prostate cancer development. Biochimica et biophysica acta 28 25017995
2022 Identifying the E2F3-MEX3A-KLF4 signaling axis that sustains cancer cells in undifferentiated and proliferative state. Theranostics 27 36276637
2020 MicroRNA‑34a expression affects breast cancer invasion in vitro and patient survival via downregulation of E2F1 and E2F3 expression. Oncology reports 27 32186770
2019 QKI-6 inhibits bladder cancer malignant behaviours through down-regulating E2F3 and NF-κB signalling. Journal of cellular and molecular medicine 27 31449345
2009 KIF14 and E2F3 mRNA expression in human retinoblastoma and its phenotype association. Molecular vision 27 19190782
2021 E2F3 drives the epithelial-to-mesenchymal transition, cell invasion, and metastasis in breast cancer. Experimental biology and medicine (Maywood, N.J.) 26 34365840
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 26 34418232
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
2008 E2F3 plays an essential role in cardiac development and function. Cell cycle (Georgetown, Tex.) 26 19029823
2022 Smad3 deficiency improves islet-based therapy for diabetes and diabetic kidney injury by promoting β cell proliferation via the E2F3-dependent mechanism. Theranostics 25 34987651
2021 lncRNA SNHG22 sponges miR‑128‑3p to promote the progression of colorectal cancer by upregulating E2F3. International journal of oncology 25 34368861
2019 Knockdown of lncRNA HOXA-AS2 Inhibits Viability, Migration and Invasion of Osteosarcoma Cells by miR-124-3p/E2F3. OncoTargets and therapy 25 31853184
2018 HIV-1 Tat protein promotes neuronal dysregulation by inhibiting E2F transcription factor 3 (E2F3). The Journal of biological chemistry 25 30591585
2004 E2F3-a novel repressor of the ARF/p53 pathway. Developmental cell 25 15177020
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
2019 The E2F3/miR-125a/DKK3 regulatory axis promotes the development and progression of gastric cancer. Cancer cell international 24 31423109
2018 E2F3 promotes cancer growth and is overexpressed through copy number variation in human melanoma. OncoTargets and therapy 24 30214236
2017 The role of miR-210, E2F3 and ephrin A3 in angiosarcoma cell proliferation. European journal of dermatology : EJD 24 28739548
2016 miR‑34a suppresses proliferation and induces apoptosis of human lens epithelial cells by targeting E2F3. Molecular medicine reports 24 27840975
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
2020 Downregulation of LINC00665 confers decreased cell proliferation and invasion via the miR-138-5p/E2F3 signaling pathway in NSCLC. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 32403047
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
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
2021 Knockdown of circRNA circ_0087378 Represses the Tumorigenesis and Progression of Esophageal Squamous Cell Carcinoma Through Modulating the miR-140-3p/E2F3 Axis. Frontiers in oncology 21 33680929
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
2015 Over-expression of miR-125a-5p inhibits proliferation in C2C12 myoblasts by targeting E2F3. Acta biochimica et biophysica Sinica 21 25733534
2021 Silencing circRNA protein kinase C iota (circ-PRKCI) suppresses cell progression and glycolysis of human papillary thyroid cancer through circ-PRKCI/miR-335/E2F3 ceRNA axis. Endocrine journal 20 33716239
2021 E2F3 promotes liver cancer progression under the regulation of circ-PRKAR1B. Molecular therapy. Nucleic acids 20 34513297
2019 Mitochondrial protein E2F3d, a distinctive E2F3 product, mediates hypoxia-induced mitophagy in cancer cells. Communications biology 20 30740539
2013 Contrasting roles of E2F2 and E2F3 in endothelial cell growth and ischemic angiogenesis. Journal of molecular and cellular cardiology 20 23603666

Missed literature

Know a paper Affinage missed for E2F3? Flag it for the maintainers and the community.

No submissions yet.