p53 Flashcards
What are the 4 main functions of p53?
Tumour suppressor
Guardian of the genome
Mutant p53 can act as oncogene
Transcription factor
Around what year was p53 discovered?
1979
p53 was originally identified by interaction with what?
Viral proteins:
Large T antigen of SV40
E1B of adenovirus
E6 of papillomavirus
What was p53 first thought to be?
An oncogene
What does p53 suppress?
Cell transformation
What is mutated in a high proportion of human cancers?
p53
What is Li-Fraumeni syndrome?
A rare, dominant-inherited cancer syndrome where patients have a germline mutation in the TP53 gene
p53 protects against cancer, true or false?
True
What type of protein is p53?
A nuclear phosphoprotein
It is a transcription factor
What form does p53 act in?
Its tetrameric form
What does p53 recognise in promoters?
A 10bp consensus sequence:
5’- Pu.Pu.Pu.C.A/T.A/T.G.Py.Py.Py -3’
What exons in p53 are mutations clustered?
In exons 5-8 (10 exons)
What amino acids in p53 are hotspots for mutations?
Amino acids 175, 248 and 273
What do mutant versions of the p53 protein interfere with?
Normal p53 function
When is p53 expressed at very low levels?
In the absence of damage
What is the half life of p53?
20 minutes
What is the main role of p53?
To define the cellular responses to different kinds of damage, but it has many other functions, both in response to stress and normal conditions
Some p53 functions can even be what?
Antagonistic (and simultaneous)
Do functions of p53 require the transcription of genes (transactivation)?
Some do and some do not
Where are the functions of p53 performed?
Some in the nucleus, some in the cytosol
How is p53 activated?
Through post-translational modifications
In terms of the p53 pro-survival function, what are basal levels of p53 regarded as?
Antioxidant
Describe the metabolism of normal cells
Oxidative phosphorylation of pyruvate in mitochondria
Describe the Warburg effect
Cancer cells mostly use aerobic glycolysis to obtain energy, instead of oxphos
What tumour suppressor gene is probably the most studied and most important?
p53
Why was p53 first thought to be an oncogene?
Because the protein detected was a mutant form
Is a mutation in p53 sufficient enough to cause cancer?
No, need some sort of inactivation of downstream pathway to become cancerous
What region of p53 is where a lot of viral proteins can bind?
SV40 T antigen binding
Which exons of p53 bind to DNA
Exons 5-8
Where do most of the phosphorylations of p53 occur?
At the start
Most activators of p53 are kinases, true or false?
True
What happens if p53 is activated outside the nucleus?
It can move to the mitochondria and help release things from the mitochondria for apoptosis for example
Can pro-survival work during apoptosis?
Yes
