FIG. 2.

Cell cycle machinery regulating progression from G₁ to S to G₂ and M phases. Cyclins and CDKs are the positive regulators of the cell cycle. CKIs (p16, p21, and p27) are the negative regulators of the cell cycle. Hypo-phosphorylated Rb sequesters E2F, which, in turn, restricts entry into S phase. Cyclin D/CDK 4,6 phosphorylates Rb, and this phosphorylation of Rb releases E2F. E2F is a transcription factor that is required for the transcription of multiple S-phase specific genes. Restriction point refers to duration in the G₁ phase, beyond which cells will continue to S phase and cell division independent of the external environment. CDK, cyclin-dependent kinases; CKIs, cyclin-dependent kinase inhibitors; Rb, retinoblastoma.