Figure 1.

The G1/S transition in mammalian cells. CycD is a sensor of mitogenic stimuli linking the cell cycle with the external environment. Growth factor‐induced cycD accumulation results in the formation of active cycD/cdk4, which overcomes inhibition by p16 and phosphorylates Rb. This crucial event marks the transition through the restriction point (R) and induces the release of E2F transcriptional repression mediated by the HDAC protein, with the consequent transactivation of genes necessary for S phase initiation and progression. The targets of mutations found in human cancer are hatched in the Figure; alterations include Rb mutations or deletions, HDAC mutations, cycD overexpression, p16 mutations, cdk4 mutations, increased degradation of p27.