Control of Cell Proliferation Flashcards
Stages of cell cycle
- G1 (growth) phase
- S (synthesis) phase
- G2 phase
- M (mitosis) phase
What is the G1 restriction point?
The point at which the cell commits to the cell cycle and no longer requires signals to complete it
What happens at the G1 restriction point?
Cell either enters cycle or becomes quiescent
What checkpoints are there?
- G1/S
- G2/M
- M
What happens at the G1/S checkpoint?
Checks for DNA damage
What happens at the G2/M checkpoint?
Checks if DNA hasn’t been replicated properly or is damaged
What happens at the M checkpoint?
Checks if there is spindle attachment failure
What enzymes regulate the cell cycle?
Cyclin dependent kinases (Cdks)
What are the 3 major Cdks and what are their functions?
- G1 Cdk = gets cell past restriction point
- G1/S Cdk = gets cell into S phase
- M Cdk = gets cell into M phase
What activate Cdks?
Cyclins
What are cyclins?
Proteins that cyclically fluctuate in concentration throughout the cycle
What are the 4 cyclins?
- Cyclin A
- Cyclin B
- Cyclin E
- Nuclear D1
How do cyclins allow mitosis to initiate?
- Cyclins accumulate in the G1, S and G2 phases
- By end of G2 enough is available to form M-Cdk complexes which initiate mitosis
What type of gene is retinoblastoma protein (pRB)?
Tumour suppressor gene
Function of pRB
Inhibits a transcription factor which promotes entry into cell cycle
What causes an increase in protein p53?
DNA damage
What does p53 do?
Activate protein p21
What does p21 do?
Inhibits Cdk
Why is the function of p21 crucial?
It prevents entry into S phase, allowing time for DNA repair
What happens when DNA damage is severe?
p53 induces apoptosis
What type of enzyme is Ras?
GTPase
What is the normal function of Ras?
- Extracellular signal molecule binds receptor
- RTK, adaptor protein then Ras-activating protein active
- Ras activated and switches GDP for GTP
- Transcription factors made
What is a key example of transcription factor made through Ras, and what is its function?
- myc
- Drives cell cycle
How can Ras cause cancer?
- Ras proto-oncogene mutates to oncogene
- Ras always ‘on’
- Lots of myc made
- Uncontrollable cell division
