The retinoblastoma protein pathway and the restriction point

Abstract

The emerging role of the retinoblastoma protein (pRb) as a major controller of the restriction point has been supported by recent discoveries, including pRb's ability to repress gene transcription by all three RNA polymerases, which suggests a link between DNA replication and cell growth. Convergent genetic and biochemical data provide new insights into the molecular events that are upstream of, at, and downstream of pRb phosphorylation, which is regulated by G1-phase cyclins and cyclin-dependent kinases (Cdks) and their inhibitors (CKIs). Major advances have also been made in our understanding of a key role of the pathway involving cyclin D, Cdks, CKIs, pRb and E2F both in commitment to traversing the cell cycle and in restraining oncogenesis.