Lecture 26 Flashcards
What drives cell cycle progression?
CDKs (Cyclin dependent kinases).
What is the cell cycle “restriction point” and what is necessary to push the cell past this point? What happens in the absence of these necessary things?
The restriction point is the point in G1 where the cell must receive signals from growth factors (mitogens) to continue through the cell cycle. In the absence of mitogens, the cell enters G0.
What do growth factors/mitogens bind to and what happens when they do?
They bind RTKs (receptor tyrosine kinases) which dimerize upon binding the growth factor. Essentially, RTKs binding growth factors is what initiates the phosphorylation cascade that pushes the cell past G1. Keep in mind the tyrosine dimers phosphorylate one another to initiate the cascade.
How does the cascade progress once a growth factor binds its RTK?
The dimerized RTK phosphorylates G-proteins or non-receptor tyrosine kinases (Cytoplasmic protein kinase cascade) which activate transcription factors.
Cell cycle progression is controlled by expression of CDKs, so what’s necessary for a CDK to be active?
- The Cdk subunit
- The proper Cyclin (theres a different one for each
phase. ) - Activating phosphorylation
- Removal of inactivating phosphorylation
- Can’t be bound by a CDKI (i.e. p21)
What is the principal mechanism for degrading cyclins?
Proteolysis
How does the G1 CDK help to upregulate G1/S CDK and E2F?
G1 CDK phosporylates RB, which then unbinds/releases E2F (a transcription factor.) E2F increases the transcription of itself and of G1/S CDK.
How does Helicase come into play during the cell cycle?
Helicase is present throughout the cell cycle. It binds DNA in G1, it is activated in S by G1/S CDK-mediated phosphorylation, and it dissociates from DNA in G2.
The cell cycle has checkpoints in all of the cell cycle stages (G1, G2, S, or M). What enforces these checkpoints, and what is the key characteristic of each checkpoint?
The checkpoints are enforced by inactivation of Cyclin/CDK complex. G1 is the major checkpoint for DNA damage. S is the checkpoint for proper DNA duplication. G2 is another checkpoint for DNA damage. M is the checkpoint for improper spindle formation.
What are the three things necessary for Cell Cycle Checkpoints to work?
- Sensors - ATM detects dsDNA breaks and ATR
detects ssDNA breaks. - Signal transducers - ATM and ATR are kinases that
activate CHK1/2, which activate effectors - Effectors - p53, when activated by CHK2, activates
p21 (a CDKI) which inhibits CDK2 (G1 CDK) –> RB not
phosphorylated –> E2F not released
