Lecture 5 - Cellular Aspects of Development – Control of the Cell Cycle Flashcards
how is the cell cycle controlled?
Process so important to get right
1) Lots of levels of control
2) Checkpoints
“Belt and braces” approach
Redundancy
what are the 3 levels of control?
1) Transcription - gene expression
2) Protein levels and stability
3) Protein activity - post-translational modifications e.g. phosphorylation
what is a model organism?
Allows us to study mechanisms in a simple system
Cost, Ethics, Ease of experiments, Conservation
Apply to more complex systems, such as humans
Very successful
Eukaryotic organisms conserved function
eg fission yeast
what is fission yeast in mitosis?
Different genes expressed at different cell cycle times
Focus on genes expressed at the start of S phase
what is the S phase genes?
Cell is making proteins at the start of S-phase exactly when they are required.
Cell economy, regulation etc.
Same for other groups of genes expressed at other cell cycle times.
Same regulation in human cells
MBF = E2F, E2F interacts with p53 and Rb
Some of these proteins mutated in cancers
Drug targets
What is protein levels and stability?
Ubiquitination and proteasome
cause specific protein degradation during cell cycle
At simplest level gene expression controls protein levels so mRNA = protein
but many proteins are stable
Must have mechanism to remove proteins
what are the 2 important cell cycle proteins?
1) CDK1 (cyclin dependent kinase) = stable
and Cyclin B = unstable
CDK1 is master controller of cell cycle
CDK1 activity is regulated by CyclinB
what do these proteins do?
Binding of Cyclin B to CDK 1 crucial for cell cycle progression from G2-M phase so unbound they are inactive but bound they are active
Removal of cyclin crucial for cell cycle progression after M-phase by Ubiquitination
or Proteasome
what happens when proteasome and ub binds?
they become inactive
what does phosphorylation do for the cell cycle?
De-phosphorylation of CDK1 crucial for cell cycle progression from G2-M phase
