FINAL-- p53: guardian of the genome #15 Flashcards
1
Q
p53 overview
A
- TF encoded by the TP53 gene (tumor suppressor)
- encodes 15 isoforms
- most frequently mutated
- maintains genome integrity
- activates when DNA is damaged
2
Q
p53 is activated in a variety of stress conditions, including:
A
- DNA damage
- Activated oncogenes
- Telomere shortening
- Spindle damage
- Hypoxia
- Metabolic stress
3
Q
p53 activation can lead to:
A
- Cell cycle arrest
- DNA repair
- Cellular senescence
-Apoptosis - inhibition of angiogenesis
4
Q
p53 Functional domains and mutational hotspots
A
- Binds as a tetramer (functioning as a TF) to a p53 response element
- binds to 300 different gene promoter regions
- regulates protein-coding genes and miRNA genes
- patterns of posttranslational modifications and interactions with binding partners correlate with distinct transcription programs
5
Q
p53 posttranslational modifications
A
enhances the ability to transcribe target gene and increase the half-life of the protein
6
Q
Consensus sequence
A
determined from 1546 p
7
Q
MDM2
A
- ubiquitin ligase to tag p53 with ubiquitin for degradation
- binds to and inhibits the TA domain
- Transports p53 into cytoplasm
8
Q
HAUSP
A
- a stabilizing factor that removes ubiquitin from p53
9
Q
Upstream activator of p53
A
- DNA damage
- Activated oncogenes
10
Q
A
