Transcriptional Control of Cell Growth: The E2F Gene Family

It is of critical importance to maintain an appropriate balance between proliferation and quiescence or differentiation through­ out the lifespan of all animals. An important control point in this balance occurs in the G, phase of the cell cycle. On the basis of environmental cues a cell in G, must decide whether to continue through the proliferative cycle and enter S phase (where DNA replication occurs) or to exit from the proliferative cycle into a nonreplicating state. Alterations in the mechanisms that nor­ mally control this decision can lead to cancer, cell death, or loss of differentiated cellular phenotypes. The identification of the E2F gene family of transcription factors has allowed a more complete understanding of how the cell maintains an appropri­ ate proliferative state. This volume provides an up-to-date ac­ count of present reports concerning E2F as well as a framework for future investigations. E2F activity requires heterodimerization of two partners. Either partner can be one of several different transcription factors; E2Fl, E2F2, E2F3, E2F4, or E2F5 can heterodimerize with either DPl or DP2. Cellular promoters whose E2F sites mediate a link between transcription and proliferation drive genes whose products are required for DNA synthesis and genes that encode regulators of cell growth. A detailed analY$is of the role that E2F family members play in transcription from these promoters is presented in the chapter by J. E. SLANSKY and P. J. FARNHAM.