What is the criteria for passing the G1 checkpoint?
- cell size is adequate
- nutrients are sufficient
- social signals are present
- DNA is undamaged
Why is the G1 checkpoint most important?
determines whether or not the cell will undergo another round of cell division
What is the criteria for passing the G2 checkpoint?
- chromosomes successfully replicated
- DNA is undamaged
What are the criteria for passing the M phase checkpoint?
- chromosomes have attached to spindle apparatus (end of prometaphase)
-chromosomes properly segregated (end of anaphase)
What two proteins work together to regulate cell cycle checkpoints?
cyclins and cdks
What are cyclins?
- amounts change throughout the cell cycle
- different types for different phases (ex: G1,G2, S, M)
- only present in large amounts when they are needed
What are CDKs?
- cyclin dependent kinases
- when they are activated by cyclins, they activate or inactivate other proteins to progress the cell cycle
- think phosphorylation (pushes cell cycle forward)
What is M Phase promoting factor (MPF)?
- cyclin B + CDK1
How is MPF regulated in interphase?
- cyclin B builds up and binds to the cdk
- the cdk is then phosphorylated at two sites (inhibitory and active sites)
How is MPF regulated at the G2 checkpoint?
phosphatase enzyme removes the inhibitory phosphate
How is MPF regulated at the M phase checkpoint?
the cyclin is degraded, inactivating the cdk1
What is the G1 checkpoint controlled by?
growth factors and tumor suppressors
What are growth factors?
-hormones that stimulate cell division
- polypeptides or small proteins
- “gas” of the cell cycle (tells it to proceed)
What are tumor suppressors?
- proteins that restrict cell division
- “brakes” of cell division
What are two G1 tumor suppressors?
- p53: DNA repair
- Rb (pRB): blocks S-phase
What is E2F?
activator of S phase (sequestered until cell is ready)
Describe how E2F is released.
-cyclin E and CDK2 causes the release of E2F from Rb
-cell cycle goes from G1 to S
What are ways that the G1 to S pathway can lead to cancer?
- Rb broken (doesn’t bind to E2F)
- overproduction of cyclin
- overactive phosphatase
-overactive cdk - too much growth factor
- too much/overactive E2F
What is the normal function of a proto-oncogene?
cause normal cells to become cancerous
What do proto-oncogenes do?
- stimulate cell growth and division
- mutations convert to oncogenes, which are mutant alleles that promote cancer development
- too much proto-oncogene–> cancerrrr
What is the function of a tumor suppressor?
- restrict cell growth and division
- removal of tumor suppressors–> cancerrrr
How does a mutation of growth factor/RAS lead to cancer?
- the RAS protein is active with or without the growth factor, so their is an overexpression of the protein at the end instead of the normal amount of protein that will stimulate the cell cycle
How does p53 mutation work in a cancer cell?
- normally used for dna repair
- when there is DNA damage in a genome, p53 can help with repair normally to produce a protein that inhibits the cell cycle
- in the mutation, there is a mutation of the p53 that is missing transcription factor, so the protein that inhibits cell division is absent
How does the environment impact cancer?
there are various carcinogens
