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Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F4 binds with high affinity to RBL1 and RBL2. In some instances can also bind RB1. Specifically required for multiciliate cell differentiation: together with MCIDAS and E2F5, binds and activate genes required for centriole biogenesis.
Gene References into Functions
E2f4 forms apical cytoplasmic organizing centres for assembly and nucleation of deuterosomes. Using genetically altered mice and E2F4 mutant proteins we demonstrate that centriole amplification is crucially dependent on these organizing centres and that, without cytoplasmic E2f4, deuterosomes are not assembled, halting multiciliogenesis PMID: 28675157
Studied expression of E2F4 in breast cancer patients undergoing neoadjuvant chemotherapy; found target gene-based signature of E2F4 can be used to predict neoadjuvant response. PMID: 28464832
The authors found that phosphorylation of residues S650 and S975 in p107 weakens the E2F4 transactivation domain binding. PMID: 27567532
This study found evidence that the number of triplet AGC repeats in the E2F4 gene may play a role in the susceptibility to early-onset colorectal cancer. PMID: 26343152
PHF8 reduces the H3K9me2 level at the E2F4 transcriptional start site, demonstrating a direct function of PHF8 in endothelial E2F4 gene regulation PMID: 26751588
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. PMID: 25650659
E2F4 promoter occupancy is globally associated with p53-repression targets, but not with p53 activation targets. PMID: 24096481
cancer-associated E2F4 mutations enhance the capacity of colorectal cancer cells to grow without anchorage, thereby contributing to tumor progression. PMID: 24100580
Short alleles (<13 repeats) of (AGC)n in E2F4 were less frequent in women with breast cancer than in the control sample. PMID: 23015403
the loss of CDH1/E2F4 may be associated with worse clinical and pathological findings in mammary ductal carcinoma. PMID: 23007606
In terminally differentiated cells, common KDM5A and E2F4 gene targets were bound by the pRB-related protein p130, a DREAM complex component. PMID: 23093672
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. PMID: 22357515
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 PMID: 22475873
Our data indicate that E2F4 is required for cardiomyocyte proliferation and suggest a function for E2F4 in mitosis PMID: 19955219
E2F4, PHACTR3, PRAME family member and CDH12 most probably play important role in non-small-cell lung cancer geneses PMID: 19473719
regulation of expression of p130, p107 and E2F-4 in human cells PMID: 12006580
data point to Tat as an adaptor protein that recruits cellular factors such as E2F-4 to exert its multiple biological activities PMID: 12055184
Mutations in E2F-4 gene is associated with hereditary non-polyposis colorectal cancer PMID: 12148576
EBV LMP1 blocks p16INK4 pathway by promoting nuclear export of E2F-4. PMID: 12860972
E2F-a and E2F-c binding sites are involved in the TCR-induced down-regulation of ICBP90 gene transcription PMID: 15964557
E2F4 is a transcriptional regulator of the cell cycle genes. PMID: 16135806
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. PMID: 17001309
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 PMID: 17043659
Evolutionarily conserved multisubunit protein complex that contains p130 and E2F4 mediates the repression of cell cycle-dependent genes in quiescence. PMID: 17531812
deregulated nuclear E2F4 expression induces apoptosis via multiple pathways in normal intestinal epithelial cells but not in colon cancer cells. PMID: 17656449
E2F4, binding sites are located within 2 kb of a transcription start site, in both normal and tumor cells PMID: 17908821
Cell cycle genes are the evolutionarily conserved targets of the E2F4 transcription factor PMID: 17957245
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. PMID: 18368381
E2F4 may be determinant in the promotion of proliferation of human intestinal epithelial crypt cells and colorectal cancer cells. PMID: 19562678
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. PMID: 17507799
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. PMID: 15231644
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Subcellular Location
Nucleus.
Protein Families
E2F/DP family
Tissue Specificity
Found in all tissue examined including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.