Zusammenfassung der Ressource
Regulation of the cell cycle
- Cyclin D + CDK 4/6
- G1 phase up to restriction point
- Cyclin E + CDK 2
- Past G1 restriction point to beginning of S phase
- Cyclin A + CDK 2
- First half of S phase
- Cyclin A + CDK 1
- Second half of S phase to end of G2
- Cyclin B + CDK1
- 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
- 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)
- 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)
- 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