Cell Growth and Differentiation Flashcards
What important protein regulates the progression of cells through the G1 checkpoint?
How does it do this?
Retinoblastoma Protein
Binds to E2F -> stimulates S-phase protein expression.
What happens when Rb after it is phosphorylated by ___ and ___?
When Rb is phosphorylated by cyclin D-CDK4 and Cyclin E-CDK2, it can no longer bind to E2F and the cell is consequently allowed to progress to the S phase. DNA replication will consequently start.
What proteins do the target genes of E2F include?
Cyclin E and S phase proteins including DNA polymerase, thymidine kinase and PCNA (protein involved in DNA replication).
What are G1 CDKs activated in response to?
• G1 CDKs are activated in response to environmental signals, late CDKs by preceding kinase activities.
What is RB hyperphosphorylated dephosphorylated by?
Protein phosphatase 1
G1 CDKs ___ and late CDKs ___.
G1 CDKs hypophosphorylate, and late CDKs hyperphosphorylate.
Unphosphorlyated RB binds to __ transcription factor and what does this prevent?
Its stimulation of S-phase protein expression.
What does released E2F stimulate?
Expression of more cyclin E and S-phase proteins e.g. DNA polymerase, thymidine kinase, PCNA etc. DNA replication starts.
Overview:
What does Rb control and when?
What can cyclin-CDK phosphorylate and what effect does this have?
- Rb controls cell cycle in all cells, when hypophophorylated/unphosphorylated it binds to E2F transcription factor
- Cyclin-CDK can phosphorylate RB, releasing E2F leading to expression of Cyclin E and other S phase proteins
Growth factor signalling activates?
Early gene expression (transcription factors – FOS, JUN, MYC)
What do early gene products stimulate?
Early gene products stimulate delayed gene expression (includes Cyclin D, CDK2/4 and E2F transcription factors)
What is E2F sequestered by?
• E2F sequestered by binding to unphosphorylated retinoblastoma protein (RB)
What do G1. cyclin-CDK complexes do to RB?
What does G1/S cyclin-CDK complexes do to RB?
G1 cyclin-CDK complexes hypophosphorylate RB and then G1/S cyclin-CDK complexes hyperphosphorylate RB releasing E2F
What does E2F stimulate the expression of?
E2F stimulates expression of more Cyclin E and S-phase proteins (e.g. DNA polymerase, thymidine kinase, Proliferating Cell Nuclear Antigen etc.)
What do S phase cyclin-CDK and G2/M cyclin-CDK complexes do?
What are these switches activated by?
• S-phase cyclin-CDK and G2/M cyclin-CDK complexes build up in inactive forms.
These switches are activated by post-translational modification or removal of inhibitors, driving the cell through S-phase and mitosis.