COMPLEX GENE NETWORK IN CELL-CYCLE REGULATION - CENTRAL ROLE OF THE E2F FAMILY OF TRANSCRIPTION FACTORS

Numerous studies indicate that transcription factors of the E2F family play the key role in cell cycle regulation. These factors determine c oordinated expression of genes that encode proteins required for cell cycle progression, e.g., cyclins, cyclin-dependent kinases, transcript ion factor E2F-1, the retinoblastoma protein pRB, DNA replication and repair enzymes, and some histones. These genes are predominantly expre ssed during the G1/S transition and early in the S phase, Tumor suppre ssor proteins p53 and pRB are involved in negative control of the cell cycle and regulate E2F functions through direct protein-protein inter actions or a complex gene network of cell cycle control, The regulator y regions of 35 genes involved in cell cycle control are described in derail in the CYCLE-TRRDatabase. Functions of E2F-binding sites, struc ture of the regulatory regions of E2F-dependent genes, and gene interr elationships in cell cycle control are discussed.