Activation of CDK4/6 in G1 Phase

  • 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.

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