ABSTRACT
The prototype of retinoblastoma (Rb) proteins, providing their name, is the retinoblastoma protein pRb, originally discovered in an eye tumor. The master regulators of cell cycle progression are the cyclin-dependent protein kinases. Aurora kinases are key regulators of cell division that cooperate but differ in substrate specificity and cellular localization. Strict regulation of cyclin-dependent kinase (CDK) activity, as required for precise cell cycle progression, depends not only on inhibitory phosphorylation but also on proteins that specifically antagonize the stimulatory effects of cyclins. Like cyclins, CDK inhibitors are short-lived proteins that are rapidly ubiquitylated and degraded in proteasomes. The G0 blockade can be overcome only by a synergistic effect of several mitogenic signals (such as hormones and growth factors) acting on the cell for several hours until the cell cycle begins to progress independently of exogenous signals. This occurs at the so-called restriction point in the late G1 phase.
