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Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription
The E2F family of transcription factors are downstream effectors of the retinoblastoma protein, pRB, pathway and are essential for the timely regulation of genes necessary for cell-cycle progression. Here we describe the characterization of human and murine E2F8, a new member of the E2F family. Sequence analysis of E2F8 predicts the presence of two distinct E2F-related DNA binding domains suggesting that E2F8 and, the recently, identified E2F7 form a subgroup within the E2F family. We show that E2F transcription factors bind the E2F8 promoter in vivo and that expression of E2F8 is being induced at the G1/S transition. Purified recombinant E2F8 binds specifically to a consensus E2F-DNA-binding site indicating that E2F8, like E2F7, binds DNA without the requirement of co-factors such as DP1. E2F8 inhibits E2F-driven promoters suggesting that E2F8 is transcriptional repressor like E2F7. Ectopic expression of E2F8in diploidhumanfibroblasts reduces expression of E2F-target genes and inhibits cell growth consistent with a role for repressing E2F transcriptional activity. Taken together, these data suggest that E2F8has an important role in turning of the expression of E2F-target genes in the S-phase of the cell cycle.
Keyword(s): E2F-target; transcription factor; pRB; retinoblastoma protein; Cancer; Genes & Society
Publication Date:
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Institution: Trinity College Dublin
Citation(s): 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 Research, 44, 17, 2005, 5458-5470
First Indexed: 2014-05-13 05:49:29 Last Updated: 2018-07-27 06:33:00