Published online 22 September 2005
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Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription
1Biotech Research & Innovation Centre (BRIC) Fruebjergvej 3, 2100 Copenhagen Ø, Denmark 2European Institute of Oncology Via Ripamonti 435, 20141 Milan, Italy 3Faculty of Health Sciences, University of Copenhagen Blegdamsvej 3, 2200 Copenhagen N, Denmark
*To whom correspondence should be addressed. Tel: +45 3917 9666; Fax: +45 3917 9669; Email: kristian.helin{at}bric.dk
Received July 13, 2005. Revised September 6, 2005. Accepted September 6, 2005.
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 E2F8 in diploid human fibroblasts 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 E2F8 has an important role in turning of the expression of E2F-target genes in the S-phase of the cell cycle.
Present address: Luisa Di Stefano, Laboratory of Molecular Oncology, Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
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