Advanced cell signalling Flashcards
describe the p53 tumour suppressor protein
53kDA protein that co-immunoprecipitated with SV40 large T-antigen
SV40= simian virus 40
where is p53 localised
on the short arm of chromosome 17
what is Li-Fraumeni syndrome
germline mutation in p53
results in attenuated tumour suppressor function
high predisposition to cancers
50% incident of cancer by age 30
describe a p53 mutation
is mutated in 50% of all cancers
most commonly mutate tumour suppressor in acer
typically a missense mutation in one allele
results in high levels of a non-functional protein
linked to poor response to therapy
how does p53 function as a tumour suppressor
p53 level are kept low under basal/normal cell growth condition
p53 activated following DNA damage via post translational modifications
p53 levels increase and it functions as a transcription factor
p53 targets genes involved in DNA repair, cell cycle arrest and apoptosis
stabilisation of p53
stress acts on all
ATM phosphorylated
p300 acetylation
SET9 methylation
PIAS sumoylation
degradation of p53
basal
ubiquitination of MDM2
post translation modification vs increase in transcription of the p53 gene
rapid
reversible
requires less energy
stress dependent
sensitive to the magnitude of stress
where are 95% of all mutations in p53 located
in the central DNA binding domain
define apoptosis
controlled and regulated mode of cell death
two types of apoptosis
extrinsic
intrinsic
what is extrinsic apoptosis
cell surface death receptor mediated
cytokine/ligand dependent
inflammation
paracrine (cell A activating cell B)
what is intrinsic apoptosis
mitochondria mediated
DNA damage
UV, chemicals, ROS
primary autocirne
what does deregulated apoptosis lead to
normal development
regulation of p53 during normal cell proliferation
tumour suppressor genes
prevent cell replication
acts as brakes so p53 produced
proto-oncogenes
allow cell replication
acts as accelerator so MDM2 produced
