Cell cycle control Flashcards
What happens in G0?
Quiescence - no DNA replication
How is DNA cycle regulated?
Phosphorylation (kinases) and dephospho rylation (phosphates) and protein degradation (ubiquitinase)
What is ubiquitination?
Addition of ubiquitin to mark proteins for degradation
Process of ubiquitination
Addition of ubiquitin tag to protein
Degradation of tag protein in proteosome
Ubiquitin activated by E1 - ATP needed
Activated U transferred to protein by E2 and E3
Are E1 and E2 enzymes specific?
yes, determined by E3
How do kinases regulate DNA cycle?
Add phosphate groups to proteins
Changes conformation
What are cyclins?
regulatory proteins
When is there the highest quantity of cyclin?
Interphase, disappears on cytokinesis
how do cyclins change over cell cycle?
G1S cyclins in G phase, decreases as S phase
M cyclins gradually increase from G2 and peak in M
How are CDKs inhibited?
Phosphorylation
CDK1 regulation
CDKs phosphorylated to inhibit activity
inactive complex
Phosphatase activated cyclin-cdk complex
CDK2 regulation
Degrading cyclin = reduction in cyclin:dk activity
Enzymes add ubiquitin groups
This highlights proteins for degradation
CDK3 regulation
Other proteins bind to cyclin:cdk complex and inactivate it
In late G1 CDKis degradant by ubiquitination
What do mitogens do?
Stimulate production of cyclins involved in early stage of cell cycle
Rb and E2F
- On RHS, mitogen binding to receptor on outside of cell
- Activates signalling pathway, increasing transcription of G1 and G1s cyclins
- Stimulate cell cycle
- On left absence of mitogen binding where transcription factors inactivated in nucleus by binding of Rb
- Rb binds E2F transcription factors
- Phosphorylation of Rb releases E2F transcription factors allowing rge interaction with transcription-activating proteins on promoters of genes required for cell cycle e.g. DNA replication
- Expression of genes required for cell cycle