Affinage

E2F5

Transcription factor E2F5 · UniProt Q15329

Length
346 aa
Mass
37.6 kDa
Annotated
2026-06-09
81 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

E2F5 is a DP-heterodimerizing transcription factor of the E2F family that, with E2F4, defines a structurally and functionally distinct subfamily and serves as the principal effector of pocket-protein-mediated transcriptional control (PMID:7892279, PMID:7760804, PMID:7542760, PMID:9464260). It heterodimerizes with DP-1 for high-affinity binding to E2F DNA sites and associates preferentially with the pocket protein p130 rather than pRb or p107 (PMID:7892279, PMID:7760804, PMID:7542760); this p130 association is required for E2F5's repressive activity in vivo, since E2F5 alone cannot oppose activator E2Fs but does so when co-expressed with p130 (PMID:18385796). Genetic ablation shows E2F5 is dispensable for normal cell-cycle progression but, redundantly with E2F4, is necessary for p16INK4a/pocket-protein-driven G1 arrest (PMID:11030352). Beyond proliferative control, E2F5 has prominent roles in terminal differentiation and secretory tissue function: its loss causes choroid plexus secretory dysfunction and hydrocephalus (PMID:9553039), impairs multiciliated cell development in efferent ducts and kidney (PMID:26825228, PMID:30218642), and is required for meiotic recombination during spermatogenesis through direct transactivation of dmc1 (PMID:32196499). In mammary epithelium E2F5 promotes alveolar progenitor differentiation and acts as a tumor suppressor whose loss, after latency, yields metastatic tumors, with chromatin effects manifest as altered H3K27me3 at luminal progenitor genes (PMID:39341991). Although classically a repressor, E2F5 functions context-dependently as a transcriptional activator at the HPV18 E6/E7, MYCN, MMP-2/MMP-9, and dmc1 promoters, in the MYCN case through an E2F5-TFDP1-BRG1 complex that deposits activating histone marks (PMID:20639900, PMID:30765227, PMID:32386317, PMID:34746136). E2F5 subcellular distribution is dynamically regulated: nuclear import depends on its N-terminal 56 residues independent of DP/pRb, CRM1 mediates its nuclear export, and differentiation cues drive its nuclear translocation (PMID:12089160). Its abundance is controlled post-transcriptionally by METTL3-dependent m6A methylation and by the RNA-binding protein IMP3, both stabilizing E2F5 mRNA (PMID:35985439, PMID:38271139).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1995 High

    Establishing that E2F5 is a bona fide E2F-family member required showing it could engage E2F DNA elements and pocket proteins; cloning revealed DP-1 heterodimerization, high-affinity DNA binding, and selective p130 association distinguishing it from pRb-binding activator E2Fs.

    Evidence Yeast two-hybrid, co-immunoprecipitation and DNA-binding assays after cloning

    PMID:7542760 PMID:7760804 PMID:7892279

    Open questions at the time
    • Did not define the in vivo target gene repertoire
    • Functional consequence of p130 selectivity not yet tested
  2. 1995 High

    Whether E2F5 was an activator or repressor was resolved by mapping a C-terminal activation domain that is inactivated upon pocket-protein binding, placing E2F4/E2F5 in a distinct functional subfamily.

    Evidence Reporter assays in yeast and mammalian cells with deletion mutagenesis

    PMID:7542760 PMID:9464260

    Open questions at the time
    • Did not establish which mode dominates at endogenous promoters
    • Co-regulators of activation/repression not identified
  3. 1998 High

    The physiological non-proliferative role was first revealed when E2F5 knockout mice developed hydrocephalus from choroid plexus secretory dysfunction without cell-cycle defects, decoupling E2F5 from canonical proliferation control.

    Evidence Homozygous knockout mice with histology, EM, and in situ hybridization

    PMID:9553039

    Open questions at the time
    • Secretory target genes in choroid plexus not identified
    • Mechanism linking E2F5 to fluid production unknown
  4. 2000 High

    Genetic redundancy with E2F4 was defined by double-knockout neonatal lethality and the failure of double-null fibroblasts to arrest in response to p16INK4a, establishing E2F4/E2F5 as the required effectors of pocket-protein G1 arrest while being dispensable for proliferation per se.

    Evidence E2F4/E2F5 double-knockout mouse genetics and p16INK4a-induced arrest assays

    PMID:11030352

    Open questions at the time
    • Did not resolve E2F4 vs E2F5 individual contributions to arrest
    • Target genes mediating arrest not enumerated
  5. 2000 Medium

    An oncogenic capacity was demonstrated by E2F5 cooperating with DP1 and activated RAS to transform primary kidney cells, hinting at a context where E2F5 drives rather than restrains growth.

    Evidence Focus-formation assay in primary BRK cells with gene mapping

    PMID:10738311

    Open questions at the time
    • Transformation in an artificial overexpression context
    • Did not identify transformation-relevant target genes
  6. 2002 High

    The basis for E2F5's regulated localization was established by mapping an N-terminal import signal independent of DP/pRb and a CRM1-dependent export region, with differentiation driving nuclear entry.

    Evidence In vitro nuclear import in permeabilized cells, leptomycin B inhibition, and deletion mutagenesis with keratinocyte immunofluorescence

    PMID:12089160

    Open questions at the time
    • Import receptor not identified
    • Signal triggering differentiation-induced translocation unknown
  7. 2008 High

    The requirement of p130 for repressive function in vivo was confirmed by showing E2F5 alone cannot block activator-E2F-driven proliferation in lens, but does so when co-expressed with p130.

    Evidence Transgenic mouse crosses with BrdU incorporation and immunohistochemistry

    PMID:18385796

    Open questions at the time
    • Did not test endogenous p130 dependence
    • Repressed target genes not catalogued
  8. 2010 Medium

    The classical repressor view was challenged by identifying E2F5 as a direct activator of HPV18 E6/E7 oncogenes that promotes S-phase entry in HPV18-positive cells, establishing context-dependent activation.

    Evidence Sequential siRNA silencing of E2F members with luciferase reporters and cell-cycle analysis

    PMID:20639900

    Open questions at the time
    • Cofactors converting E2F5 to activator not defined
    • Specificity for HPV18 vs cellular promoters unclear
  9. 2011 Medium

    Post-transcriptional control of E2F5 repressor activity was linked to disease by showing mutant-p53-induced miR-128-2 targets E2F5, relieving its repression of p21 and driving chemoresistance.

    Evidence Reporter assays, miRNA overexpression/knockdown and ChIP in NSCLC cells

    PMID:22193543

    Open questions at the time
    • Direct E2F5 binding at p21 promoter not shown in this study
    • Generality beyond NSCLC unknown
  10. 2015 High

    Direct promoter targets in differentiation were defined by ChIP showing E2F5 represses the differentiation inhibitors ID1 and HMOX1 downstream of miR-98 to control myogenesis.

    Evidence Transcriptomics, miRNA target validation, ChIP, and double-knockdown epistasis in myoblasts

    PMID:25422988

    Open questions at the time
    • Cofactor requirements at these promoters not defined
    • Whether repression requires p130 not tested
  11. 2016 High

    Tissue-specific developmental roles in ciliogenesis were established by conditional E2f4/E2f5 deletion eliminating multiciliated and absorptive cells in efferent ducts, causing male sterility from defective fluid absorption.

    Evidence Conditional knockout mouse genetics with histology and immunohistochemistry

    PMID:26825228

    Open questions at the time
    • Direct ciliogenesis target genes not identified
    • Division of labor between E2F4 and E2F5 unresolved
  12. 2016 Medium

    A proliferative signaling axis was proposed in prostate cancer wherein E2F5 acts with p38 to drive linker-region SMAD3 phosphorylation, with co-knockdown causing G1 arrest.

    Evidence siRNA knockdown with Western blot and cell-cycle analysis in PC3 cells and patient tissue

    PMID:26919443

    Open questions at the time
    • Direct transcriptional targets of the axis not defined
    • Whether E2F5 regulates p38 directly unknown
  13. 2018 High

    Species-specific dominance within the subfamily was revealed in zebrafish where E2f5, not E2f4, is the essential factor for multiciliated cell development in kidney tubules.

    Evidence Zebrafish mutant and double-mutant genetics with whole-mount immunostaining

    PMID:30218642

    Open questions at the time
    • Molecular basis for E2f4/E2f5 functional swap between species unknown
    • Ciliogenesis targets not identified
  14. 2019 Medium

    E2F5 was embedded in oncogenic transcriptional circuits by showing MYCN directly induces E2F5, and E2F5 knockdown reduces CDK2/CDK6 and proliferation in MYCN-amplified neuroblastoma.

    Evidence ChIP, luciferase reporter, siRNA knockdown and Western blot

    PMID:30765227

    Open questions at the time
    • Whether E2F5 directly activates CDK2/CDK6 not shown
    • Feedback onto MYCN not addressed here
  15. 2019 Medium

    E2F5 was shown to act as a transcriptional activator in a feed-forward differentiation circuit by binding the lncPCAT1 promoter to drive BMP2 and osteogenic differentiation in periodontal stem cells.

    Evidence ChIP, luciferase reporter, miRNA sponge validation and differentiation assays

    PMID:30997692

    Open questions at the time
    • Cofactors enabling activation not defined
    • Generality across stem cell types unknown
  16. 2020 High

    Direct activator/repressor duality at metastasis genes was demonstrated by ChIP showing E2F5 represses TFPI2 while activating MMP-2/MMP-9 to promote prostate cancer invasion.

    Evidence ChIP-qPCR with site-directed mutagenesis, reporter assays, zymography and Co-IP in tissue

    PMID:32386317

    Open questions at the time
    • Determinants of activation vs repression at the same factor not defined
    • Partner proteins at these promoters not identified
  17. 2020 High

    The in vivo developmental and meiotic program was defined by zebrafish showing E2F5 directly transactivates dmc1 to enable meiotic recombination during spermatogenesis, with dmc1 overexpression rescuing fertility, plus jagged2b activation regulating multiciliated cell fate.

    Evidence Zebrafish mutant genetics, transcriptomics, ChIP on dmc1, and dmc1 rescue with e2f5;tp53 double mutants

    PMID:32196499

    Open questions at the time
    • Cofactors enabling dmc1 activation not identified
    • Conservation of dmc1 regulation in mammals not tested
  18. 2020 Medium

    An anti-apoptotic role was established by showing E2F5 knockdown induces TP53-target pro-apoptotic genes only in wild-type-TP53 breast cancer cells, defining a TP53-dependent suppression of apoptosis.

    Evidence siRNA knockdown with TP53 co-silencing epistasis and cell-death assays in MCF7

    PMID:33000282

    Open questions at the time
    • Mechanism linking E2F5 to TP53 target repression not defined
    • Direct binding at BAX/NOXA/PUMA promoters not shown
  19. 2021 Medium

    A physical partner and feedback loop driving E2F5 abundance were identified: CDK13 binds E2F5 and a circCDK13/miR-212-5p/449a axis relieves E2F5 repression to amplify proliferation.

    Evidence Co-IP/mass spectrometry, CRISPR endogenous activation and gain/loss-of-function in vitro and in vivo

    PMID:33390186

    Open questions at the time
    • Functional consequence of direct CDK13-E2F5 binding (e.g., phosphorylation) not defined
    • Reciprocal validation of the interaction limited
  20. 2021 Medium

    The mechanism of context-dependent activation was advanced by showing an E2F5-TFDP1-BRG1 complex binds the MYCN promoter and deposits H3 acetylation and H3K4me3 to recruit RNA Pol II during liver regeneration.

    Evidence RNAi, ChIP for BRG1/E2F5/TFDP1, histone modification analysis and MYCN rescue in BRG1-null hepatocytes

    PMID:34746136

    Open questions at the time
    • Whether the same complex operates at other activated promoters not tested
    • Direct E2F5-BRG1 contact not mapped
  21. 2021 Low

    E2F5 was linked to gastric cancer growth by transcriptional upregulation of UBE2T, with UBE2T rescue reversing the phenotype of E2F5 depletion.

    Evidence siRNA knockdown, GSEA, transcription regulation assay and UBE2T rescue

    PMID:34583905

    Open questions at the time
    • No ChIP confirming direct UBE2T promoter binding
    • Single lab without mechanistic characterization
  22. 2022 Medium

    Post-transcriptional stabilization of E2F5 was defined by demonstrating METTL3-dependent m6A methylation increases E2F5 mRNA stability, with E2F5 overexpression rescuing the anti-tumor effect of METTL3 loss in pancreatic cancer.

    Evidence MeRIP assay, RT-qPCR, Western blot and rescue experiments

    PMID:35985439

    Open questions at the time
    • m6A reader mediating stabilization not identified
    • Site-level m6A mapping on E2F5 not shown
  23. 2024 Medium

    A second RNA-based stability mechanism was established by showing IMP3 directly binds E2F5 mRNA and prolongs its half-life, supporting OSCC proliferation.

    Evidence RNA immunoprecipitation, mRNA stability assay, siRNA knockdown and xenograft

    PMID:38271139

    Open questions at the time
    • Relationship between IMP3 and METTL3 m6A regulation not addressed
    • Binding site on E2F5 mRNA not mapped
  24. 2024 High

    The mammary tumor-suppressor and differentiation role was defined by conditional knockout showing E2F5 promotes alveolar progenitor differentiation via H3K27me3 control at luminal progenitor genes, with loss eventually producing metastatic tumors.

    Evidence Mammary-specific conditional knockout with scRNAseq, H3K27me3 chromatin profiling, RNAseq, WGS and transplantation

    PMID:39341991

    Open questions at the time
    • Mechanism connecting E2F5 to H3K27me3 deposition unknown
    • Driver events of late metastatic tumors not fully resolved
  25. 2025 Medium

    A vascular disease role was added by showing E2F5 promotes VSMC phenotypic switching in diabetic atherosclerosis through Wnt/β-catenin activation, with CyclinE rescuing E2F5 silencing.

    Evidence siRNA knockdown, CyclinE rescue, pharmacological Wnt modulation and in vivo DAS mouse model

    PMID:40890020

    Open questions at the time
    • Direct E2F5 targets in the Wnt axis not identified
    • Whether E2F5 acts upstream or parallel to Wnt unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what molecular switch converts E2F5 between p130-dependent repression and BRG1/cofactor-dependent activation at individual promoters, and how its differentiation, tumor-suppressor, and oncogenic roles are selected in a given tissue.
  • No general rule for activation vs repression specificity
  • Tissue-context determinants of tumor-suppressor vs oncogenic output unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 2
Partners
BRG1CDK13RBL2TFDP1
Complex memberships
E2F5-DP1 heterodimerE2F5-TFDP1-BRG1 complexE2F5-p130 repressor complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 E2F-5 protein was cloned and shown to heterodimerize with DP-1, enabling high-affinity binding to E2F DNA recognition sequences. E2F-5 preferentially interacts with p130 (not pRb) in a yeast two-hybrid assay, in contrast to E2F-1, -2, and -3 which bind pRb. Yeast two-hybrid, co-immunoprecipitation, DNA binding assays Proceedings of the National Academy of Sciences of the United States of America High 7542760 7760804 7892279
1995 E2F-5 contains a potent transcriptional activation domain in its C-terminal region that functions in both yeast and mammalian cells and is specifically inactivated upon pocket protein binding. E2F-5 and E2F-4 define a subfamily structurally and functionally distinct from E2F-1, -2, and -3. Reporter gene assays in yeast and mammalian cells, deletion mutagenesis, two-hybrid assays Oncogene High 7542760 9464260
1995 Under physiological conditions, E2F-5 interacts preferentially with p130 (not pRb or p107) as demonstrated by specific antiserum immunoprecipitation from cell extracts. Co-immunoprecipitation with specific E2F-5 antiserum Molecular and cellular biology High 7760804
1998 E2F-5 knockout mice develop nonobstructive hydrocephalus with excessive CSF production from the choroid plexus. E2F-5 CNS expression is largely confined to the choroid plexus, and its loss affects secretory behavior of this differentiated neural tissue without perturbing cell cycle kinetics in knockout fibroblasts. Gene targeting (homozygous knockout mice), histology, electron microscopy, in situ hybridization Genes & development High 9553039
2000 Simultaneous inactivation of E2F4 and E2F5 in mice results in neonatal lethality. Embryonic fibroblasts from E2F4/E2F5 double-knockout mice fail to arrest in G1 in response to p16INK4a, demonstrating that E2F4 and E2F5 are dispensable for cell cycle progression but necessary for pocket protein-mediated G1 arrest. Double-knockout mouse genetics, cell cycle analysis, p16INK4a-induced arrest assay Molecular cell High 11030352
2000 E2F5 gene (mapped to 8q21.1-21.3) can promote morphologically transformed foci in primary baby rat kidney cells when overexpressed with DP1 and activated RAS, demonstrating oncogenic cooperation analogous to MYC-type cooperating oncogenes. Focus formation assay in primary BRK cells, gene mapping, copy number analysis in breast tumors Genes, chromosomes & cancer Medium 10738311
2002 E2F-5 nuclear import requires only the first N-terminal 56 amino acids and is independent of DP or pRB family proteins. E2F-5 is exported from the nucleus via CRM1-mediated (leptomycin B-sensitive) transport through a region corresponding to amino acid residues 130-154, which excludes the DNA- and p130-binding domains. Keratinocyte differentiation drives E2F-5 nuclear translocation. In vitro nuclear import assays in digitonin-permeabilized cells, leptomycin B inhibition, deletion mutant analysis, immunofluorescence in keratinocytes The Journal of biological chemistry High 12089160
2005 E2F5 protein localizes to the nucleus in immature/proliferating choroid plexus epithelial cells and shifts to the cytoplasm as cells mature (change from pseudostratified to cuboidal epithelium), a change that does not correlate with PCNA-positive proliferating cells but parallels morphological maturation. Immunohistochemistry, in situ hybridization, PCNA co-staining in mouse and human developing choroid plexus The International journal of developmental biology Medium 16172982
2007 E2F5 and LEK1 translocate to the nucleus as an early event in Raf/MEK/ERK-driven myoblast quiescence. Disruption of MEK1 activity prevents ERK1/2 phosphorylation and nuclear translocation of E2F5 and LEK1. E2F5 and LEK1 are found in nuclei of non-dividing satellite cells and myonuclei in vivo. Proteomics (2D-gel + MS), immunofluorescence, pharmacological MEK inhibition, in vivo satellite cell staining Journal of cellular biochemistry Medium 17295207
2008 Overexpression of E2F5 alone is not sufficient to inhibit E2F1- or E2F3a-induced cell cycle reentry in lens fiber cells in vivo. However, coexpression of E2F5 together with p130 inhibits activator E2F-mediated cell proliferation, confirming that p130 is required for E2F5's repressive activity. Transgenic mouse crossing experiments, BrdU incorporation, immunohistochemistry, in situ hybridization Molecular vision High 18385796
2010 E2F5 acts as a direct transcriptional activator (not repressor) of HPV18 E6/E7 oncogenes by binding E2F sites specific to HPV18 in HeLa cells. Sequential silencing of E2F family members identified E2F5 as the activator. E2F5 also positively regulates S-phase entry specifically in HPV18-expressing cells. Sequential siRNA silencing of E2F family members, luciferase reporter assays, cell cycle analysis Oncogene Medium 20639900
2011 miR-128-2, induced by mutant p53 (p53R175H), post-transcriptionally targets E2F5 and abrogates its repressive activity on p21(waf1) transcription. Loss of E2F5 repression leads to cytoplasmic p21 accumulation which prevents pro-caspase-3 cleavage, contributing to chemoresistance in non-small-cell lung cancer. Reporter assays, Western blot, miRNA overexpression/knockdown, ChIP for mutant p53 on ARPP21 promoter Cell death and differentiation Medium 22193543
2015 E2F5 is a direct target of miR-98 in human myoblasts, and E2F5 binds to the promoters of the differentiation inhibitors ID1 and HMOX1, repressing their expression. Simultaneous knockdown of E2F5 and miR-98 restores normal skeletal muscle differentiation, placing E2F5 downstream of miR-98 in regulating myogenesis. Transcriptomic analysis, direct miRNA target validation, ChIP on ID1 and HMOX1 promoters, genetic epistasis by double knockdown The Biochemical journal High 25422988
2016 E2F5 overexpression is associated with elevated p38 phosphorylation and SMAD3 phosphorylation at the linker region (Ser-208, pSMAD3L) in prostate cancer. Downregulation of E2F5 and p38 by siRNA in PC3 cells reduces SMAD3 phosphorylation and causes G1 cell cycle arrest, defining an E2F5/p38/SMAD3 axis in prostate cancer proliferation. siRNA knockdown, Western blot, immunostaining, qRT-PCR, cell cycle analysis Journal of cellular physiology Medium 26919443
2016 E2f4 and E2f5 are required for the development of multiciliated cells and absorptive cells in efferent ducts; conditional deletion of E2f4 in Vil-cre;E2f5+/- males eliminates multiciliated cells and reduces aquaporin1 and clusterin expression in efferent ducts, causing male sterility due to defective fluid absorption. Conditional knockout mouse genetics (Vil-cre;E2f4f/f;E2f5+/-), histology, immunohistochemistry Cell cycle (Georgetown, Tex.) High 26825228
2018 In zebrafish, E2f5 is essential for MCC development in kidney tubules, while E2f4 is dispensable. Using double mutant combinations, E2f5 has a more prominent role than E2f4 in zebrafish MCC development, contrasting with the mouse where E2f4 appears dominant. Zebrafish mutant genetics, double mutant analysis, whole mount immunostaining Developmental biology High 30218642
2019 MYCN directly binds an E-Box motif in the E2F5 gene promoter to induce its transcription, as confirmed by ChIP and reporter assays. E2F5 knockdown in MYCN-amplified neuroblastoma cells inhibits proliferation and reduces CDK2 and CDK6 expression. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, siRNA knockdown, Western blot Biochemical and biophysical research communications Medium 30765227
2019 E2F5 can bind to the promoter of lncPCAT1 in periodontal ligament stem cells, forming a feed-forward regulatory network in which E2F5 drives lncPCAT1 expression which in turn sponges miR-106a-5p to upregulate BMP2, promoting osteogenic differentiation. ChIP assay, luciferase reporter assay, miRNA sponge validation, osteogenic differentiation assays in vitro and in vivo Journal of cellular physiology Medium 30997692
2020 E2F5 promotes prostate cancer cell migration and invasion by acting as a transcriptional activator/repressor at TFPI2, MMP-2, and MMP-9 promoters. ChIP with anti-E2F5 IgG confirmed E2F5 recruitment to these promoters; E2F5 represses TFPI2 and activates MMP-2/MMP-9, increasing gelatinolytic activity. RNAi knockdown, pathway-focused gene expression profiling, ChIP-qPCR, site-directed mutagenesis, dual-luciferase assay, Proteome Profiler array, gelatin zymography, co-immunoprecipitation in tissue Carcinogenesis High 32386317
2020 E2F5 knockout in zebrafish causes spermatogenesis arrest at the zygotene stage due to homologous recombination defects and germ cell apoptosis. E2F5 directly binds the promoter of dmc1 (meiotic recombination protein) to promote its transcription; overexpression of dmc1 rescues fertilization in e2f5 mutant males. E2f5 also activates the Notch pathway gene jagged2b to inhibit MCC fate acquisition by neighboring principal cells. Zebrafish mutant genetics, transcriptome analysis, ChIP on dmc1 promoter, dmc1 rescue by overexpression, double mutant analysis (e2f5;tp53) PLoS genetics High 32196499
2020 E2F5 knockdown in wild-type TP53-bearing breast cancer cells (MCF7) induces cell death through upregulation of TP53-target pro-apoptotic genes (BAX, NOXA, PUMA). This effect is abrogated by TP53 silencing and is not observed in mutant TP53 cells, indicating E2F5 suppresses TP53-mediated apoptosis in a TP53-dependent manner. siRNA knockdown, real-time RT-qPCR, TP53 co-silencing epistasis experiment, cell death assays Oncology reports Medium 33000282
2021 CDK13 physically interacts with E2F5 (confirmed by Co-IP coupled to mass spectrometry) and this interaction strengthens the pro-proliferation effect of CDK13. Transcriptional activation of CDK13 promotes E2F5 protein expression by facilitating circCDK13 biogenesis, which sponges miR-212-5p/449a to relieve repression of E2F5, forming a positive feedback loop. Co-immunoprecipitation plus mass spectrometry, CRISPR-Cas9 endogenous activation, loss/gain-of-function assays in vitro and in vivo Journal of experimental & clinical cancer research : CR Medium 33390186
2021 An E2F5-TFDP1-BRG1 complex binds the MYCN promoter in hepatocytes to drive MYCN transcription during liver regeneration. BRG1 is recruited by E2F5/TFDP1 and promotes histone H3 acetylation and H3K4 trimethylation at the MYCN promoter, facilitating RNA polymerase II binding. RNA interference validation of E2F5 and TFDP1, ChIP for BRG1/E2F5/TFDP1 at MYCN promoter, histone modification analysis, MYCN overexpression rescue in BRG1-null hepatocytes Frontiers in cell and developmental biology Medium 34746136
2021 E2F5 directly upregulates UBE2T transcription in gastric cancer cells, as confirmed by correlation analysis and transcriptional regulation assays. E2F5 depletion inhibits proliferation and invasion, and UBE2T overexpression reverses these effects. siRNA knockdown, GSEA, correlation analysis, transcription regulation assay, rescue by UBE2T overexpression Digestive and liver disease Low 34583905
2022 METTL3 promotes E2F5 mRNA stability through m6A methylation of E2F5 transcripts, as demonstrated by MeRIP assay. Silencing METTL3 decreases E2F5 expression and inhibits pancreatic cancer cell viability; overexpression of E2F5 reverses the anti-tumor effects of METTL3 knockdown. MeRIP assay (m6A methylation), RT-qPCR, Western blot, CCK-8, rescue experiments Cellular signalling Medium 35985439
2024 IMP3 (RNA-binding protein) binds E2F5 mRNA directly (confirmed by RNA immunoprecipitation), and silencing IMP3 shortens E2F5 mRNA half-life and reduces E2F5 protein expression, thereby inhibiting OSCC cell proliferation. RNA immunoprecipitation (RIP), mRNA stability assay, siRNA knockdown, in vivo xenograft Aging Medium 38271139
2024 Mammary-specific conditional knockout of E2F5 results in delayed alveolar expansion during early pregnancy with reduced E2F target gene expression. E2F5 deletion leads to enrichment of luminal progenitor populations at the expense of differentiated alveolar cells, with depletion of the repressive H3K27me3 mark at luminal progenitor-associated genes. After prolonged latency, E2F5 conditional knockout mice develop highly metastatic mammary tumors with altered Cyclin D1 levels. scRNAseq, mammary-specific conditional knockout, chromatin profiling (H3K27me3), RNAseq, whole genome sequencing, transplantation assay, Western blot Oncogene High 39341991
2024 E2F5 loss leads to delayed alveolar expansion during early pregnancy with reduced proliferation (decreased canonical E2F target gene expression) and a block in luminal progenitor differentiation into alveolar precursors, associated with depletion of H3K27me3 at luminal progenitor genes. E2F5 chromatin binding increases during early pregnancy. Mammary epithelial-specific conditional knockout, scRNAseq, chromatin profiling, RNAseq bioRxivpreprint Medium
2025 E2F5 promotes VSMC phenotypic switching in diabetic atherosclerosis through activation of the Wnt/β-catenin pathway. E2F5 knockdown inhibits phenotypic transformation of VSMCs, and CyclinE overexpression reverses this inhibition. BML-284 (Wnt activator) attenuates the inhibitory effect of E2F5 silencing. siRNA knockdown, CyclinE overexpression rescue, pharmacological Wnt pathway modulation (BML-284), in vivo DAS mouse model, Western blot Diabetes & metabolism journal Medium 40890020

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle. Proceedings of the National Academy of Sciences of the United States of America 326 7892279
2000 E2F4 and E2F5 play an essential role in pocket protein-mediated G1 control. Molecular cell 237 11030352
1995 E2F-5, a new E2F family member that interacts with p130 in vivo. Molecular and cellular biology 223 7760804
1998 A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting. Genes & development 153 9553039
2017 SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5. Biochemical and biophysical research communications 139 28232182
2011 MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function. Cell death and differentiation 134 22193543
2018 The putative tumour suppressor miR-1-3p modulates prostate cancer cell aggressiveness by repressing E2F5 and PFTK1. Journal of experimental & clinical cancer research : CR 65 30185212
2016 The transcription factor FOXN3 inhibits cell proliferation by downregulating E2F5 expression in hepatocellular carcinoma cells. Oncotarget 52 27259277
1995 Molecular and functional characterisation of E2F-5, a new member of the E2F family. Oncogene 52 7542760
2016 MicroRNA-154 inhibits growth and invasion of breast cancer cells through targeting E2F5. American journal of translational research 51 27398145
2014 Up-regulated MicroRNA-181a induces carcinogenesis in hepatitis B virus-related hepatocellular carcinoma by targeting E2F5. BMC cancer 50 24529171
2021 CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 contributes to prostate carcinogenesis. Journal of experimental & clinical cancer research : CR 48 33390186
2016 E2f4 and E2f5 are essential for the development of the male reproductive system. Cell cycle (Georgetown, Tex.) 48 26825228
2019 Long noncoding RNA SNHG6 functions as a competing endogenous RNA by sponging miR-181a-5p to regulate E2F5 expression in colorectal cancer. Cancer management and research 46 30666158
2011 A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma. World journal of gastroenterology 46 21274376
2009 Overexpression of E2F-5 correlates with a pathological basal phenotype and a worse clinical outcome. British journal of cancer 43 19259095
2016 miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells. American journal of translational research 40 27186275
2015 MicroRNA-34a targets FMNL2 and E2F5 and suppresses the progression of colorectal cancer. Experimental and molecular pathology 40 26103003
2010 E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer. BMC cancer 40 20181230
2000 Human E2F5 gene is oncogenic in primary rodent cells and is amplified in human breast tumors. Genes, chromosomes & cancer 40 10738311
2018 MicroRNA-1179 inhibits the proliferation, migration and invasion of human pancreatic cancer cells by targeting E2F5. Chemico-biological interactions 39 29859832
2017 MiR-613 suppresses retinoblastoma cell proliferation, invasion, and tumor formation by targeting E2F5. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 38 28351331
2018 Induction of apoptosis in ovarian cancer cells by miR-493-3p directly targeting AKT2, STK38L, HMGA2, ETS1 and E2F5. Cellular and molecular life sciences : CMLS 37 30392041
2016 miRNA-154-5p Inhibits Proliferation, Migration and Invasion by Targeting E2F5 in Prostate Cancer Cell Lines. Urologia internationalis 37 27074041
2019 A feed-forward regulatory network lncPCAT1/miR-106a-5p/E2F5 regulates the osteogenic differentiation of periodontal ligament stem cells. Journal of cellular physiology 36 30997692
2002 Active nuclear import and export pathways regulate E2F-5 subcellular localization. The Journal of biological chemistry 36 12089160
2018 MicroRNA-129-3p suppresses tumor growth by targeting E2F5 in glioblastoma. European review for medical and pharmacological sciences 35 29509253
2020 E2f5 is a versatile transcriptional activator required for spermatogenesis and multiciliated cell differentiation in zebrafish. PLoS genetics 34 32196499
2020 E2F5 promotes prostate cancer cell migration and invasion through regulation of TFPI2, MMP-2 and MMP-9. Carcinogenesis 33 32386317
2020 Circular RNA ABCB10 promotes non-small cell lung cancer progression by increasing E2F5 expression through sponging miR-584-5p. Cell cycle (Georgetown, Tex.) 32 32420810
2018 Distinct requirements of E2f4 versus E2f5 activity for multiciliated cell development in the zebrafish embryo. Developmental biology 29 30218642
2017 miRNA-34a enhances the sensitivity of gastric cancer cells to treatment with paclitaxel by targeting E2F5. Oncology letters 29 28599485
2013 Effects of microRNA-106 on proliferation of gastric cancer cell through regulating p21 and E2F5. Asian Pacific journal of cancer prevention : APJCP 29 23803041
2020 LncRNA MALAT1 Regulates the Progression and Cisplatin Resistance of Ovarian Cancer Cells via Modulating miR-1271-5p/E2F5 Axis. Cancer management and research 26 33116856
2016 Deregulated E2F5/p38/SMAD3 Circuitry Reinforces the Pro-Tumorigenic Switch of TGFβ Signaling in Prostate Cancer. Journal of cellular physiology 25 26919443
2022 METTL3 promotes the growth and metastasis of pancreatic cancer by regulating the m6A modification and stability of E2F5. Cellular signalling 23 35985439
2005 Changes in E2F5 intracellular localization in mouse and human choroid plexus epithelium with development. The International journal of developmental biology 23 16172982
2013 Analysis of genetic aberrations on chromosomal region 8q21-24 identifies E2F5 as an oncogene with copy number gain in prostate cancer. Medical oncology (Northwood, London, England) 22 23377984
2021 CircFAM13B promotes the proliferation of hepatocellular carcinoma by sponging miR-212, upregulating E2F5 expression and activating the P53 pathway. Cancer cell international 19 34348712
2019 MYCN-induced E2F5 promotes neuroblastoma cell proliferation through regulating cell cycle progression. Biochemical and biophysical research communications 17 30765227
2019 miR‑132 inhibits high glucose‑induced vascular smooth muscle cell proliferation and migration by targeting E2F5. Molecular medicine reports 16 31257477
2006 Involvement of protein kinase C and E2F-5 in euxanthone-induced neurite differentiation of neuroblastoma. The international journal of biochemistry & cell biology 16 16546434
2021 Downregulation of long non-coding RNA UCA1 represses tumorigenesis and metastasis of osteosarcoma via miR-513b-5p/E2F5 axis. Anti-cancer drugs 15 33595944
2015 miR-98 delays skeletal muscle differentiation by down-regulating E2F5. The Biochemical journal 15 25422988
2021 An E2F5-TFDP1-BRG1 Complex Mediates Transcriptional Activation of MYCN in Hepatocytes. Frontiers in cell and developmental biology 14 34746136
2010 The E2F5 repressor is an activator of E6/E7 transcription and of the S-phase entry in HPV18-associated cells. Oncogene 14 20639900
2021 E2F5 promotes proliferation and invasion of gastric cancer through directly upregulating UBE2T transcription. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 13 34583905
2018 Let-7c Inhibits the Proliferation, Invasion, and Migration of Glioma Cells via Targeting E2F5. Oncology research 13 29362021
2007 E2F5 and LEK1 translocation to the nucleus is an early event demarcating myoblast quiescence. Journal of cellular biochemistry 13 17295207
1998 The molecular and functional characterization of E2F-5 transcription factor. Biochemical and biophysical research communications 13 9464260
2020 MicroRNA-1271-5p inhibits the tumorigenesis of ovarian cancer through targeting E2F5 and negatively regulates the mTOR signaling pathway. Panminerva medica 12 32414231
2008 Thyroid hormone - triiodothyronine - has contrary effect on proliferation of human proximal tubules cell line (HK2) and renal cancer cell lines (Caki-2, Caki-1) - role of E2F4, E2F5 and p107, p130. Thyroid research 12 19014670
2021 Targeting CALM2 Inhibits Hepatocellular Carcinoma Growth and Metastasis by Suppressing E2F5-mediated Cell Cycle Progression. Anticancer research 11 33788723
1995 Structural characterization and specificity of expression of E2F-5: a new member of the E2F family of transcription factors. Cellular & molecular biology research 11 8589754
2023 MAPK Is a Mutual Pathway Targeted by Anxiety-Related miRNAs, and E2F5 Is a Putative Target for Anxiolytic miRNAs. Biomolecules 9 36979479
2023 LINC01980 induced by TGF-beta promotes hepatocellular carcinoma metastasis via miR-376b-5p/E2F5 axis. Cellular signalling 9 37827344
2021 E2F5 Promotes the Malignancy of Ovarian Cancer Via the Regulation of Hippo and Wnt Pathways. Genetic testing and molecular biomarkers 9 33734894
2020 Knockdown of E2F5 induces cell death via the TP53‑dependent pathway in breast cancer cells carrying wild‑type TP53. Oncology reports 9 33000282
2022 CircFOXM1 promotes the proliferation, migration, invasion, and glutaminolysis of glioblastoma by regulating the miR-577/E2F5 axis. Bosnian journal of basic medical sciences 8 34784267
2008 Overexpression of E2F5/p130, but not E2F5 alone, can inhibit E2F-induced cell cycle entry in transgenic mice. Molecular vision 8 18385796
2021 Inhibition of HDACs Suppresses Cell Proliferation and Cell Migration of Gastric Cancer by Regulating E2F5 Targeting BCL2. Life (Basel, Switzerland) 6 34947956
2001 [Differences in human and rat FSH receptors promote activity as a result of the transcriptional factors: E2F1, E2F4 and E2F5 overexpression]. Ginekologia polska 6 11883315
2019 MicroRNA‑34a inhibits esophageal squamous cell carcinoma progression by targeting E2F5. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 5 31983127
2023 E2F5 Targeted by Let-7d-5p Facilitates Cell Proliferation, Metastasis and Immune Escape in Gallbladder Cancer. Digestive diseases and sciences 4 38087129
2022 hsa_circ_0084811 Regulates Cell Proliferation and Apoptosis in Retinoblastoma through miR-18a-5p/miR-18b-5p/E2F5 Axis. BioMed research international 4 35909488
2016 Aberrant Promoter Methylation at CpG Cytosines Induce the Upregulation of the E2F5 Gene in Breast Cancer. Journal of breast cancer 4 27382388
2024 Knockdown of RNA-binding protein IMP3 suppresses oral squamous cell carcinoma proliferation by destabilizing E2F5 transcript. Aging 3 38271139
2024 Insight into mammary gland development and tumor progression in an E2F5 conditional knockout mouse model. Oncogene 3 39341991
2009 Identification and expression analysis of two zebrafish E2F5 genes during oogenesis and development. Molecular biology reports 3 19578977
2025 Investigating the clinical significance of E2F5 expression in circulating extracellular vesicles in prostate carcinoma. Urologia 1 39907045
2025 E2F5 Accelerates Vascular Smooth Muscle Cells Phenotype Switching in Diabetic Atherosclerosis through Activating Wnt/β-Catenin Pathway. Diabetes & metabolism journal 1 40890020
2024 Retracted: hsa_circ_0084811 Regulates Cell Proliferation and Apoptosis in Retinoblastoma through miR-18a-5p/miR-18b-5p/E2F5 Axis. BioMed research international 1 38550126
2023 [Effects of lncRNA SNHG12 on the proliferation, migration and invasiveness of prostate cancer cells by regulating E2F5 expression]. Zhonghua nan ke xue = National journal of andrology 1 37847082
2026 Crosstalk Between FOXN3 and E2F5 Reveals a Novel Tumor Suppressive Pathway in Acute Myeloid Leukemia via MAPK Signaling: Implications for Potential Future Targeted Therapy. Blood and lymphatic cancer : targets and therapy 0 41908971
2026 E2F5 Promotes Vascular Endothelial Cell Proliferation and Angiogenesis in Diabetic Lower Limb Ischemia via an Autophagy-Related Mechanism. Circulation journal : official journal of the Japanese Circulation Society 0 41987367
2026 An Integrated Graphene-MXene Electrochemical Transistor Array Platform for Accurate Prostate Cancer Diagnosis Using Plasma sEV-Derived E2F5 Biomarker. Small (Weinheim an der Bergstrasse, Germany) 0 42057744
2025 circ_0000132 Regulates Chicken Granulosa Cell Proliferation Apoptosis and E2/P4 Synthesis via miR-206 E2F5 Signaling. International journal of molecular sciences 0 41226814
2025 E2F5 Overexpression in Laryngeal Squamous Cell Carcinoma: Associations With Neutrophil Extracellular Traps in the Tumor Microenvironment. World journal of oncology 0 41488283
2025 Fu Zheng Xiao Yu San Jie Decoction affects the proliferation of renal cell carcinoma via regulating E2F5 gene. Translational andrology and urology 0 41522321
2023 Long Noncoding RNA SNHG6 Functions as a Competing Endogenous RNA by Sponging miR-181a-5p to Regulate E2F5 Expression in Colorectal Cancer [Retraction]. Cancer management and research 0 37228644
2022 miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells [Retraction]. American journal of translational research 0 35173889

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