Property Summary

NCBI Gene PubMed Count 83
PubMed Score 183.73
PubTator Score 128.95

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (3)

Disease Target Count P-value
ovarian cancer 8491 7.8e-10
malignant mesothelioma 3163 2.6e-06
osteosarcoma 7933 2.4e-05
Disease Target Count Z-score Confidence
Cardiovascular system disease 194 0.0 2.0
Disease Target Count Z-score Confidence
Cancer 2346 4.456 2.2

Expression

  Differential Expression (3)

Disease log2 FC p
malignant mesothelioma 1.400 2.6e-06
osteosarcoma -1.561 2.4e-05
ovarian cancer 1.500 7.8e-10

Gene RIF (41)

PMID Text
26751588 PHF8 reduces the H3K9me2 level at the E2F4 transcriptional start site, demonstrating a direct function of PHF8 in endothelial E2F4 gene regulation
26369285 cell cycle-dependent transcription of the TRAIP gene by E2F1, E2F2, and E2F4 and rapid protein degradation leads to cell cycle-dependent expression with a maximum in G2/M
25712098 Data suggest that aberrant cell cycle activation in Ewing sarcoma is due to the de-repression of transcription factor E2F targets of transcriptional induction and physical recruitment of E2F3 by fusion protein EWS-FLI1 replacing E2F4 on their promoters.
25650659 Authors show that BRCA1 and RAD17 genes, whose derived proteins play a pivotal role in DNA damage repair, are transcriptional targets of gain-of-function mutant p53 proteins.
24109597 Analysis data from a panel of cell cycle transcription factors (E2F1, E2F4, E2F6, and GABPA) finds that a set of core cell cycle genes regulated in both U2OS and HeLa cells are bound by multiple cell cycle transcription factors.
24100580 cancer-associated E2F4 mutations enhance the capacity of colorectal cancer cells to grow without anchorage, thereby contributing to tumor progression.
24096481 E2F4 promoter occupancy is globally associated with p53-repression targets, but not with p53 activation targets.
23093672 In terminally differentiated cells, common KDM5A and E2F4 gene targets were bound by the pRB-related protein p130, a DREAM complex component.
23060449 Trim28 regulates cell proliferation by bridging HDAC1 and E2F3 and E2F4 interactions.
23015403 Short alleles (<13 repeats) of (AGC)n in E2F4 were less frequent in women with breast cancer than in the control sample.
23007606 the loss of CDH1/E2F4 may be associated with worse clinical and pathological findings in mammary ductal carcinoma.
22688350 The inverse immunohistochemical relationship between E2F1 and E2F4 indicates a possible mechanistic interlink in colorectal cancer.
22475873 data demonstrate that enforced E2F4 expression in Burkitt lymphoma (BL) cells not only diminishes E2F1 levels, but also reduces selectively the tumorigenic properties and proliferation of BL cells
22357515 Silica could induce the high expression of cyclin D1 and CDK4 and the low expression of E2F-4, resulting in the cell cycle changes by AP-1/cyclin D1 pathway in human embryonic lung fibroblasts.
21789246 Tamoxifen resistant tumors displayed enriched expression of genes related to cell cycle and proliferation, as well as elevated activity of E2F transcription factors.
21048031 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19955219 Our data indicate that E2F4 is required for cardiomyocyte proliferation and suggest a function for E2F4 in mitosis
19738611 Observational study of gene-disease association. (HuGE Navigator)
19562678 E2F4 may be determinant in the promotion of proliferation of human intestinal epithelial crypt cells and colorectal cancer cells.
19473719 E2F4, PHACTR3, PRAME family member and CDH12 most probably play important role in non-small-cell lung cancer geneses
18660489 Observational study of gene-disease association. (HuGE Navigator)
18368381 FBI-1 is the first transcriptional repressor shown to act as a dual regulator in adipogenesis exerting repressor activities on target genes by both, direct and indirect mechanisms.
17957245 Cell cycle genes are the evolutionarily conserved targets of the E2F4 transcription factor
17908821 E2F4, binding sites are located within 2 kb of a transcription start site, in both normal and tumor cells
17656449 deregulated nuclear E2F4 expression induces apoptosis via multiple pathways in normal intestinal epithelial cells but not in colon cancer cells.
17531812 Evolutionarily conserved multisubunit protein complex that contains p130 and E2F4 mediates the repression of cell cycle-dependent genes in quiescence.
17507799 By interacting with p130, E2F4 plays a key role in the maintenance of a stable G2 arrest. Increased E2F4 levels and its translocation to the nucleus following genotoxic stress result in downregulation of mitotic genes.
17121828 Wnt/beta-catenin signaling may contribute to colorectal carcinogenesis by reducing the level of the E2F4 cell cycle repressor via an antisense mechanism
17043659 in response to radiation, E2F4 becomes active in the nucleus, enforces a stable G(2) arrest by target gene repression, and thus provides increased cell survival ability by minimizing propagation of cells that have irreparable DNA damage
17001309 Hypoxia induces substantial p130 dephosphorylation and nuclear accumulation, leading to the formation of E2F4/p130 complexes and increased occupancy of E2F4 and p130 at the RAD51 and BRCA1 promoters.
16758952 There were no significant changes of CDK4 and E2F-1/4 expression in benzo(a)pyrene treated embryo lung fibroblasts.
16135806 E2F4 is a transcriptional regulator of the cell cycle genes.
15964557 E2F-a and E2F-c binding sites are involved in the TCR-induced down-regulation of ICBP90 gene transcription
15231644 Increased E2F4/p130 complex formation seen after irradiation depended on increased nuclear E2F4, dissociation of p130 from Cdk2, and p130 dephosphorylation. E2F4 siRNA prevented p130/E2F4 formation and sensitized cells to radiation-induced apoptosis.
12860972 EBV LMP1 blocks p16INK4 pathway by promoting nuclear export of E2F-4.
12789259 We investigated occupancy of ER-alpha promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a link between pRb2/p130 and chromatin-modifying enzymes in the regulation of ER-alpha transcription
12148576 Mutations in E2F-4 gene is associated with hereditary non-polyposis colorectal cancer
12055184 data point to Tat as an adaptor protein that recruits cellular factors such as E2F-4 to exert its multiple biological activities
12055184 Binding of HIV-1 Tat to E2F4 is mediated through amino acids 1-49 of Tat and 1-184 of E2F4, allowing Tat to recruit E2F4 to promoter elements to exert its multiple biological activities
12006580 regulation of expression of p130, p107 and E2F-4 in human cells
11759817 expression reduced in primary and metastatic breast carcinoma

AA Sequence

MAEAGPQAPPPPGTPSRHEKSLGLLTTKFVSLLQEAKDGVLDLKLAADTLAVRQKRRIYDITNVLEGIGL      1 - 70
IEKKSKNSIQWKGVGPGCNTREIADKLIELKAEIEELQQREQELDQHKVWVQQSIRNVTEDVQNSCLAYV     71 - 140
THEDICRCFAGDTLLAIRAPSGTSLEVPIPEGLNGQKKYQIHLKSVSGPIEVLLVNKEAWSSPPVAVPVP    141 - 210
PPEDLLQSPSAVSTPPPLPKPALAQSQEASRPNSPQLTPTAVPGSAEVQGMAGPAAEITVSGGPGTDSKD    211 - 280
SGELSSLPLGPTTLDTRPLQSSALLDSSSSSSSSSSSSSNSNSSSSSGPNPSTSFEPIKADPTGVLELPK    281 - 350
ELSEIFDPTRECMSSELLEELMSSEVFAPLLRLSPPPGDHDYIYNLDESEGVCDLFDVPVLNL           351 - 413
//

Text Mined References (90)

PMID Year Title
26751588 2016 The Histone Demethylase PHF8 Is Essential for Endothelial Cell Migration.
26369285 2015 The TRAF-interacting protein (TRAIP) is a novel E2F target with peak expression in mitosis.
25712098 2015 EWS-FLI1 employs an E2F switch to drive target gene expression.
25650659 2015 Gain of function mutant p53 proteins cooperate with E2F4 to transcriptionally downregulate RAD17 and BRCA1 gene expression.
25100735 2014 Post-transcriptional gene expression control by NANOS is up-regulated and functionally important in pRb-deficient cells.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24109597 2013 Identification of cell cycle-regulated genes periodically expressed in U2OS cells and their regulation by FOXM1 and E2F transcription factors.
24100580 2013 Functional impact of colorectal cancer-associated mutations in the transcription factor E2F4.
24096481 2014 p53-dependent gene repression through p21 is mediated by recruitment of E2F4 repression complexes.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23093672 2012 Coordinated repression of cell cycle genes by KDM5A and E2F4 during differentiation.
23060449 2012 Tripartite motif containing 28 (Trim28) can regulate cell proliferation by bridging HDAC1/E2F interactions.
23015403 2012 Microsatellite polymorphisms in the EGFR, NOTCH4 and E2F4 genes and their association with breast cancer risk.
23007606 2012 Covariation of copy number located at 16q22.1: new evidence in mammary ductal carcinoma.
22810586 2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.
22688350 2014 The relationship between E2F family members and tumor growth in colorectal adenocarcinomas: A comparative immunohistochemical study of 100 cases.
22475873 2012 E2F4 plays a key role in Burkitt lymphoma tumorigenesis.
22357515 2011 [The roles of activated protein-1 and cell cycle protein in silica-induced cell cycle changes].
22002537 2012 Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence.
21789246 2011 An integrated bioinformatics approach identifies elevated cyclin E2 expression and E2F activity as distinct features of tamoxifen resistant breast tumors.
21454377 2011 MiR-15 and miR-16 are direct transcriptional targets of E2F1 that limit E2F-induced proliferation by targeting cyclin E.
21347282 2011 Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.
21048031 2011 Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph.
19955219 2010 E2F4 is required for cardiomyocyte proliferation.
19738611 2009 Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis.
19562678 2009 E2F4 expression is required for cell cycle progression of normal intestinal crypt cells and colorectal cancer cells.
19473719 2010 Identification of genes associated with non-small-cell lung cancer promotion and progression.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19054851 2008 Human protein factory for converting the transcriptome into an in vitro-expressed proteome,.
18660489 2008 Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations.
18368381 2008 Transcription factor FBI-1 acts as a dual regulator in adipogenesis by coordinated regulation of cyclin-A and E2F-4.
17957245 2007 Cell cycle genes are the evolutionarily conserved targets of the E2F4 transcription factor.
17908821 2007 A comprehensive ChIP-chip analysis of E2F1, E2F4, and E2F6 in normal and tumor cells reveals interchangeable roles of E2F family members.
17671431 2007 LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes.
17656449 2007 Nuclear expression of E2F4 induces cell death via multiple pathways in normal human intestinal epithelial crypt cells but not in colon cancer cells.
17531812 2007 Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence.
17507799 2007 E2F4 function in G2: maintaining G2-arrest to prevent mitotic entry with damaged DNA.
17159899 2007 The human synMuv-like protein LIN-9 is required for transcription of G2/M genes and for entry into mitosis.
17121828 2007 An antisense transcript induced by Wnt/beta-catenin signaling decreases E2F4.
17043659 2007 E2F4 regulates a stable G2 arrest response to genotoxic stress in prostate carcinoma.
17001309 2007 Repression of RAD51 gene expression by E2F4/p130 complexes in hypoxia.
16758952 2006 [Benzo(a)pyrene induced changes of cyclin D1, CDK4 and E2F-1/4 expression in human embryo lung fibroblasts].
16360038 2005 Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release.
16135806 2005 Pocket protein complexes are recruited to distinct targets in quiescent and proliferating cells.
16061792 2005 Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600.
15964557 2005 TCR pathway involves ICBP90 gene down-regulation via E2F binding sites.
15616553 2004 The sequence and analysis of duplication-rich human chromosome 16.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15231644 2004 Genotoxic stress induces expression of E2F4, leading to its association with p130 in prostate carcinoma cells.
15107404 2004 Liver tumors escape negative control of proliferation via PI3K/Akt-mediated block of C/EBP alpha growth inhibitory activity.
14532282 2003 HCF-1 functions as a coactivator for the zinc finger protein Krox20.
12860972 2003 Epstein-Barr virus LMP1 blocks p16INK4a-RB pathway by promoting nuclear export of E2F4/5.
12789259 2003 pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-alpha in breast cancer.
12757710 2003 Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12198120 2002 Ectopic expression of necdin induces differentiation of mouse neuroblastoma cells.
12150994 2002 E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression.
12148576 2002 E2F-4 mutation in hereditary non-polyposis colorectal cancer.
12110166 2002 E2Fs regulate adipocyte differentiation.
12096339 2002 Ectopic expression of cyclin E in estrogen responsive cells abrogates antiestrogen mediated growth arrest.
12055184 2002 Physical and functional interaction of HIV-1 Tat with E2F-4, a transcriptional regulator of mammalian cell cycle.
12006580 2002 Distinct phosphorylation events regulate p130- and p107-mediated repression of E2F-4.
11759817 2001 Expression of E2F-1 and E2F-4 is reduced in primary and metastatic breast carcinomas.
11602203 2001 The human melanocyte: a model system to study the complexity of cellular aging and transformation in non-fibroblastic cells.
11573202 2001 pRb2/p130 and p107 control cell growth by multiple strategies and in association with different compartments within the nucleus.
11418595 2001 E2F transcriptional activation requires TRRAP and GCN5 cofactors.
11158323 2001 E2F4 is exported from the nucleus in a CRM1-dependent manner.
11025371 2000 Multiple tumors and a novel E2F-4 mutation. A case report.
11012981 2000 Microsatellite instability and alteration of E2F-4 gene in adenosquamous and squamous cell carcinomas of the stomach.
11005809 2000 Opposite functions for E2F1 and E2F4 in human epidermal keratinocyte differentiation.
10867026 2000 Glucocorticoids inhibit developmental stage-specific osteoblast cell cycle. Dissociation of cyclin A-cyclin-dependent kinase 2 from E2F4-p130 complexes.
10797289 2000 Genomic structure and mutation screening of the E2F4 gene in human tumors.
10679953 2000 Various AGC repeat numbers in the coding region of the human transcription factor gene E2F-4.
10540350 1999 Modulation of E2F activity in primary mouse B cells following stimulation via surface IgM and CD40 receptors.
10488129 1999 In vivo structure of two divergent promoters at the human PCNA locus. Synthesis of antisense RNA and S phase-dependent binding of E2F complexes in intron 1.
10208422 1999 Transcriptional repression of the E2F-1 gene by interferon-alpha is mediated through induction of E2F-4/pRB and E2F-4/p130 complexes.
10090723 1999 Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F-DP.
10082561 1999 C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers of newborn mice.
9724731 1998 The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase.
9688145 1998 Differential activities of E2F family members: unique functions in regulating transcription.
9271426 1997 Induction of S-phase entry by E2F transcription factors depends on their nuclear localization.
9244350 1997 BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases.
9190208 1997 Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation.
9144196 1997 The subcellular localization of E2F-4 is cell-cycle dependent.
9074408 1997 The predominant E2F complex in human primary haemopoietic cells and in AML blasts contains E2F-4, DP-1 and p130.
8657117 1996 E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry.
8643455 1996 Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases.
7958925 1994 E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo.
7958924 1994 E2F-4, a new member of the E2F transcription factor family, interacts with p107.
7892279 1995 E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle.