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A more recent version of this article appeared on May 6, 2005
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M501410200v1
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Papers In Press, published online ahead of print February 18, 2005
J. Biol. Chem, 10.1074/jbc.M501410200
Submitted on February 7, 2005
Revised on February 18, 2005
Accepted on February 15, 2005

Cloning and characterization of mouse E2F8, a novel mammalian E2F family member capable of blocking cellular proliferation

Baidehi Maiti, Jing Li, Alain de Bruin, Faye Gordon, Cynthia Timmers, Rene Opavsky, Kaustubha Patil, John Tuttle, Whitney Cleghorn, and Gustavo Leone

Ohio State University, Columbus, Ohio 43210

Corresponding Author: leone-1{at}medctr.osu.edu

The E2F transcription factor family plays a crucial and well-established role in cell cycle progression. Deregulation of E2F activities in vivo leads to developmental defects and cancer. Based on current evidence in the field, mammalian E2Fs can be functionally categorized into either transcriptional activators (E2F1, E2F2 and E2F3a) or repressors (E2F3b, E2F4, E2F5, E2F6 and E2F7). We have identified a novel E2F family member, E2F8, which is conserved in mice and humans and has its counterpart in Arabidopsis thaliana (E2Ls). Interestingly, E2F7 and E2F8 share unique structural features that distinguish them from other mammalian E2F repressor members, including the presence of two distinct DNA-binding domains and the absence of DP-dimerization, Retinoblastoma-binding, and transcriptional activation domains. Like E2F7, over-expression of E2F8 significantly slows down the proliferation of primary mouse embryonic fibroblasts. These observations, together with the fact that E2F7 and E2F8 can homodimerize and are expressed in the same adult tissues, suggest that they may have overlapping and perhaps synergistic roles in the control of cellular proliferation.


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