Gene ID: 1874 E2F transcription factor 4, "The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein binds to all three of the tumor suppressor proteins pRB, p107 and p130, but with higher affinity to the last two. It plays an important role in the suppression of proliferation-associated genes, and its gene mutation and increased expression may be associated with human cancer."[3]
Structure
The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids (Asp + Glu), and a tumor suppressor protein association domain which is embedded within the transactivation domain.
"The AGC triplet repeat in the coding region of the E2F-4 gene, a member of the family, has been reported to be mutated in colorectal cancers with a microsatellite instability (MSI) phenotype. We found a wider range variation of the repeat number in DNAs from tumors, the corresponding normal mucosa, and healthy individuals. A total of 5 repeat variants, ranging from 8 to 17 AGC repeats, was detected in 6 (9.7%) of the 62 healthy individuals and 8 (8.9%) of the 90 normal DNAs of the patients. The wild-type 13 repeat was present in all of these individuals. The variation of the AGC repeat number may be a polymorphism. Further, loss of heterozygosity (LOH) at the E2F-4 locus in the tumor tissues of 2 (25%) of the 8 informative cases was detected."[5]
↑RefSeqJuly2008 (25 December 2016). "E2F4 E2F transcription factor 4 [ Homo sapiens (human) ]". U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information. Retrieved 2017-01-08.
↑Chen CR, Kang Y, Siegel PM, Massagué J (July 2002). "E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression". Cell. 110 (1): 19–32. doi:10.1016/S0092-8674(02)00801-2. PMID12150994.
Bandyopadhyay D, Timchenko N, Suwa T, et al. (2001). "The human melanocyte: a model system to study the complexity of cellular aging and transformation in non-fibroblastic cells". Exp. Gerontol. 36 (8): 1265–75. doi:10.1016/S0531-5565(01)00098-5. PMID11602203.
Beijersbergen RL, Kerkhoven RM, Zhu L, et al. (1994). "E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo". Genes Dev. 8 (22): 2680–90. doi:10.1101/gad.8.22.2680. PMID7958925.
Williams CD, Linch DC, Sørensen TS, et al. (1997). "The predominant E2F complex in human primary haemopoietic cells and in AML blasts contains E2F-4, DP-1 and p130". Br. J. Haematol. 96 (4): 688–96. doi:10.1046/j.1365-2141.1997.d01-2086.x. PMID9074408.
Wang H, Shao N, Ding QM, et al. (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". Oncogene. 15 (2): 143–57. doi:10.1038/sj.onc.1201252. PMID9244350.
Furukawa Y, Iwase S, Kikuchi J, et al. (1999). "Transcriptional repression of the E2F-1 gene by interferon-alpha is mediated through induction of E2F-4/pRB and E2F-4/p130 complexes". Oncogene. 18 (11): 2003–14. doi:10.1038/sj.onc.1202500. PMID10208422.
