Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
The transcription factor E2F plays crucial roles in induction of S phase in mammalian cells by regulating the expression of genes that encode molecules involved in cell cycle progression. E2F exerts a repressive effect on E2F-responsive genes in G0/G1 phase by associating with the retinoblastoma tumor suppressor gene product pRb and the related protein p130. This repression is relieved by phosphorylation of the pRb family proteins by G1 cyclin (cyclin D and cyclin E) -dependent kinases, resulting in expression of E2F-responsive genes in late G1 with a peak at the G1/S boundary. One group of genes influenced by E2F encode cell cycle regulatory molecules, including members of the E2F family and cyclin E, demonstrating a loop-type regulation of activities of E2F and cyclin E-dependent kinase at this stage in the cell cycle. Another group is involved in DNA replication, including genes for molecules regulating initiation of DNA replication. Overexpression of E2F is sufficient to induce DNA synthesis in serum starved fibroblasts. In addition, overexpression of cyclin E, which is essential for entry into S phase, overcomes G1 arrest caused by inhibition of E2F activity without resuming E2F mediated transcription, suggesting the mergence of the two pathways. Thus, E2F target-gene products and cyclin E-dependent kinase activity apparently co-operate to initiate replication of DNA.