L13- Control of proliferation and differentiation Flashcards
What are the different cyclin/cdk complexes?
M-phase cyclin/cdk
G1-phase cyclin/cdk
G1/s-phase cyclin/cdk
S-phase cyclin/cdk
What are all the cyclin/cdk complexes regulated by?
Cyclin synthesis/degradation
Phosphorylation of the cdk subunit
If there is no signal to enter cell cycle what does the cell do?
Enters phase G0
Which cells spend most of their life in G0?
Neurones and muscle cells
What determines cell division rate? (eg liver cells divide once a year, gut stem cells twice a day)
Variation in time spent in G1 or G0
What needs to be present after division to enter G1?
Stimulus- growth factor, enough nutrients/atp
What’s checked at the G1 checkpoint?
Enough nutrients? Growth factor present? Is cell big enough? Is DNA undamaged?
If these are all yes- ENTER S PHASE, replicate DNA
If there isnt enough growth facot, nutrients, if the cell isnt big enough or DNA damaged what does the cell do?
It remains in G1 until it’s fixed. Doesn’t enter S phase
What’s checked at G2 checkpoint?
Is Dna replicated?
Is cell big enough?
Is DNA undamaged
If all are yes- couples S phase to M phase— mitotic spindle assembles.
How is the cell cycle stopped?
Inhibitor proteins stopping cyclin/cdk complexes
How does p53 stop the cell cycle entering S phase?
In the absence of DNA damage p53 is degraded.
If DNA is damaged it activates p21 (activated transcription of p21) which is a cdk inhibitor protein. This binds onto the cyclin/cdk complex and makes it inactive.
Can’t enter S phase.
How does DNA damage affect M-Cdk?
It inhibits activating phosphatase (cdc25) so M-Cdk isn’t activated. It can’t enter the cell cycle.
What are the mechanisms at the checkpoints?
G1-S- Cdk inhibitors block entry to S phase
G2-M- INhibition of activating phosphatases (cdc25) blocks entry to mitosis
M-G1- Inhibition of APC activation delays exit from mitosis
What’s the difference between growth and proliferation?
Growth- cell gets bigger
Proliferation- cells divide, needs growth or cells would get smaller.
What are the 3 functions of growth factors?
- Growth factors to stimulate cell growth
- Mitogens to stimulate cell division
- survival factors to promote cell survival, by suppressing apoptosis.
Most growth factors stimulate many cell types. Which one doesn’t?
Erythropoeitin- only has receptors on red blood cells
How do mitogenic growth factors stimulate cell proliferation?
Growth factors bind to receptor-> causes intracellular signalling pathway–> increases protein synthesis and decreases protein degradation.
So there’s no Rb. Cell cycle enters S phase
What is Rb?
Retinoblastoma protein. Rb suppresses transcription. proteins needed for S-phase are not made. Cells cannot enter S phase.
Growth factors phosphorylate Rb. Rb present when there’s no mitogenic growth factor,
What is myostatin an example of?
A growth inhibitor protein. Inhibits Cdk in muscle growth and proliferation. Mutation in myostatin causes super muscly cows etc.
Some growth factors inhibit proliferation by activating cdk inhibitor proteins..
In summary what are S phase and G1 phase cyclin/cdk complexes regulated by?
- Phosphorylation
- Cyclin synthesis/degradation
- Inhibitor proteins
What does p53 do in summary?
Arrests the cell in G1 upon DNA damage
What are growth factors needed for?
Mammalian cell growth (can be division, growth or survival)
What do growth factors lead to?
Activation of G phase cyclin/cdks, which phosphorylate Rb, leading to transcription of genes needed for S phase
What do mitogenic growth factors do?
Increase cell number
