- Cyclin-dependent kinases CDK4 and CDK6 (CDK4/6) play important roles in controlling the G1 phase progression, particularly passing the cells through mitogens/growth factors-dependent restriction point.
- CDK4/6 kinases phosphorylate not only Retinoblastoma proteins (pRb, p107, and p130) but also other proteins that are required for promoting the G1 phase progression and suppressing the cellular senescence and apoptosis.
- CDK4/6 requires their regulatory subunit D-type cyclins to form holoenzyme.
- The regulatory subunit, D-type cyclins (Cyclin D1, D2, and D3), are synthesized in response to mitogenic signalings.
- In addition, CIP/KIP family proteins have been reported to be required for Cyclin D-CDK4/6 assembly.
- The assembled complex is transported to the nucleus where the T-loop of the catalytic CDK subunit is phosphorylated by CAK making the holoenzyme active.
