Figure 2.

Pocket proteins connect outside signals with the cell cycle control system regulating cell proliferation. А. Direct sequence of the cell cycle phases. B. Basic components of the cell cycle control system. Mitogens induce synthesis of cyclin D which forms active kinase complexes with Cdk4-6. Cyclin D is under negative control of p15^Ink4b/p16^Ink4a inhibitors. Cyclin D/Cdk4-6 phosphorylate pRb and liberate E2fs which promote synthesis of cyclins E/A/B required for initiation and progression of DNA replication and mitosis. Cyclins eventually phosphorylate pRb until end of mitosis. p21^Cip1, p27^Kip1 and p57^Kip2 are CdkI inhibiting Cyclin E/A; SCF and APC are ubiquitin ligases promoting periodical inactivation and degradation of the cell cycle regulatory proteins.