avoiding growth suppressors

Question 1

how was p53 discovered?

Answer 1

co-precipitated with T-antigen from SV40

Question 2

how was p53 demonstrated to prevent cell transformation?

Answer 2

mutation (deletion or point mutation) to p53 allows transformation in presence of oncogenic Ras, WT p53 prevents cell transformation in presence of oncogenic Ras

Question 3

what is p53?

Answer 3

nuclear phosphoprotein - TF that acts in tetrameric form to recognise a 10bp consensus sequence in promoter regions

Question 4

where do most mutations to p53 occur?

Answer 4

in DBD - clustered in exons 5-8

Question 5

how is p53 regulated?

Answer 5

feedback mechanism with mdm2.

increased expression of p53 triggers transcription of mdm2, which moves p53 to the cytoplasm for proteasomal destruction

Question 6

what are the cellular responses to p53?

Answer 6

mediates apoptosis by intrinsic and extrinsic pathways, controls cell cycle arrest & senescence. other functions include DNA repair, antiangiogenesis

Question 7

how does p53 function in low stress conditions?

Answer 7

as an antioxidant (for ROS produced in resp), DNA repair and promotion of cell survival

Question 8

how does p53 function in high stress conditions?

Answer 8

pro-oxidant, promotion of senescence, promotes apoptosis

Question 9

what is CDKN2A?

Answer 9

gene responsible for generation of p16 - a cdk inhibitor that slows cell cycle progression by inhibiting G1/S phase progression as part of the p53 pathway

Question 10

what is ARF?

Answer 10

alternative reading frame of CDKN2A locus, functions to inhibit mdm2 sequestration to the nucleolus, activating p53. has cell cycle arrest ability that is independent of p53. induced mainly after oncogenic stress