Regulation of the cell cycle

Cyclin D + CDK 4/6
1. G1 phase up to restriction point
Cyclin E + CDK 2
1. Past G1 restriction point to beginning of S phase
Cyclin A + CDK 2
1. First half of S phase
Cyclin A + CDK 1
1. Second half of S phase to end of G2
Cyclin B + CDK1
1. M phase
Cyclin/CDK complexes are activated by the addition of 1 phosphate group by CAK
Cyclin/CDK complexes are inhibited by the addition of a second phosphate group by Wee1 kinase
1. Phosphorylation can be activating or inhibitory
The inhibitory second phosphate group can be removed by Cdc25 phosphatase
CDK inhibitors (CKI's) are proteins that bind to and inhibit Cyclin/CDK complexes (inhibit cell cycle)
1. E.g. P27 = suppresses G1/S CDK activity. P21 = suppresses CDK activity after DNA damage. P16 = stops Cyclin D/CDK 4/6 activity
Cyclins A + B contain a destruction box. Cyclins D + E contain a PEST sequnce (P - proline, E = glutamic acid, S - serine, T - threonine)
1. These are protein sequences that allow the cyclins to undergo ubiquitination and be marked for destruction by ubiquitin ligase complexes
Rb is usually bound to the transcriptional factor E2F. Cyclin D/CDK 4 complex phosphorylates Rb causing it to release the E2F protein which go on to activate genes required for cell replication and thus push the cell past the G1 restriction point
p53 is usually bound to Mdm2 that marks it for ubiquitination. DNA damage causes activating phosphorylation of p53 which then binds to the regulatory region of the p21 gene and causes its transcription. p21 then inhibits the cell cycle

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Regulation of the cell cycle

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	Created by Holly Rogers about 7 years ago