Tumour Supressor Genes Flashcards
What happens when Ras is mutated?
It’s permanently active stimulating signalling cascade
Is the mutation of ras dominant or recessive?
Dominant
Are tumour suppressor mutations dominant or recessive?
Recessive
What is a diploid cell?
Two copies of each chromosome so having one mutate is enough to maintain humour suppressor gene
What do tumour suppressor genes do?
Inhibit cell division
What was the first tumour suppressor gene identified?
Retinoblastoma protein
What are the two forms of retinoblastoma?
Familial (children)
Sporadic (adults))
Is the condition of retinoblastoma recessive or dominant?
Recessive
What is retinoblastoma caused by?
Inherited and somatic mutation
Mitotic recombination
Why does retinoblastoma inhibit?
G1-S transition
There’s a loss of G1 checkpoint
What is the role of p53?
Protect the cell against damaged DNA
Why is it called p53?
Size of protein is 53KDa
What is the role of P53?
Recognised genetic damage, metabolic stress
It’s a transcription factor
When is P53 stabilised?
Presence of genetic damage or cellular stress
If DNA is too severe what happens?
Senescence or death (apoptosis)
Explain the process of activating p53
DNA is damaged
Signal is passed to p53 via a cascade of protein kinases each phosphorylating and activating each other
Activated p53 is a transcription factor which triggers expression of protein which inhibit cell cycle
How does p53 alter gene expression using p21?
Expression regulated by p53
P22 is inhibitor of Cyclin E-Cdk2
Prevents G1 exit causing call to arrest
How does p53 alter gene expression by DNA repair proteins?
Expression regulated by p53
Allows cell to repair DNA during cell cycle arrest
If DNA is damage isnt repaired cells enter senescence or apoptosis
Define apoptosis
A form of cell death in which programmed sequence oh events leads to the elimination of cells without releasing harmful substances
How does apoptosis work?
Normal cell deluded that DNA is beyond repair and so p53 activates apoptosis
Cell shrinks and invagination form at cell surface
What factors induce apoptosis?
Signal within cell (Intrinsic apoptosis)
Activation of FAS death receptor (extrinsic apoptosis)
(Both regulated by p53)
How is intrinsic apoptosis regulated by p53?
DNA is damaged p53 induces Bid expression
Activated Bid induces Bax to form a pore in the mitochondrial membrane
Release of cytochrome c activates caspases presenting cytoplasm og cell leading to apoptosis
How is extrinsic apoptosis regulated by p53?
Activation of p53 induces expression of death receptors
Death receptors are activated by cells expressing Fas ligand eg lymphocytes
Fas ligand activates Fas death receptor and recruits FADD
Formation of the DISC activates caspases that regulate cellular disintegration (apoptosis)
