4yo2

Structural highlights

Function

[E2F8_HUMAN] Atypical E2F transcription factor that participates in various processes such as angiogenesis and polyploidization of specialized cells. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1: component of a feedback loop in S phase by repressing the expression of E2F1, thereby preventing p53/TP53-dependent apoptosis. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene.^{[1] [2] [3] [4]}

References

1. ↑ Logan N, Graham A, Zhao X, Fisher R, Maiti B, Leone G, La Thangue NB. E2F-8: an E2F family member with a similar organization of DNA-binding domains to E2F-7. Oncogene. 2005 Jul 21;24(31):5000-4. PMID:15897886 doi:http://dx.doi.org/10.1038/sj.onc.1208703
2. ↑ Christensen J, Cloos P, Toftegaard U, Klinkenberg D, Bracken AP, Trinh E, Heeran M, Di Stefano L, Helin K. Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription. Nucleic Acids Res. 2005 Sep 22;33(17):5458-70. Print 2005. PMID:16179649 doi:http://dx.doi.org/10.1093/nar/gki855
3. ↑ Zalmas LP, Zhao X, Graham AL, Fisher R, Reilly C, Coutts AS, La Thangue NB. DNA-damage response control of E2F7 and E2F8. EMBO Rep. 2008 Mar;9(3):252-9. doi: 10.1038/sj.embor.7401158. Epub 2008 Jan 18. PMID:18202719 doi:http://dx.doi.org/10.1038/sj.embor.7401158
4. ↑ Weijts BG, Bakker WJ, Cornelissen PW, Liang KH, Schaftenaar FH, Westendorp B, de Wolf CA, Paciejewska M, Scheele CL, Kent L, Leone G, Schulte-Merker S, de Bruin A. E2F7 and E2F8 promote angiogenesis through transcriptional activation of VEGFA in cooperation with HIF1. EMBO J. 2012 Oct 3;31(19):3871-84. doi: 10.1038/emboj.2012.231. Epub 2012 Aug 17. PMID:22903062 doi:http://dx.doi.org/10.1038/emboj.2012.231