p53 Flashcards
Li-Fraumeni syndrome
One mutated copy of the TP53gene
Where is the TP53 gene located?
chromosome 17p13.1
What does overactivity of TP53 cause?
Immune hyperactivation and premature ageing
What controls gene production in TP53?
2 transactivation domains (TAD1 and TAD 2)
What do genes activated by p53 do?
Growth arrest
Repair
Apoptosis
Angiogenesis block
What are transposable elements?
New elements added to a genome (from ancient viruses)
What gives p53 such a wide range of functions and binding abilities?
Internal promoter
Alternative splicing
Alternative initiation of the translation
How many protein domains does p53 contain?
6
How many exomes does p53 have?
11
How many proteins can p53 make?
12
What do p53 proteins do when they accumulate?
Bind to selected gene promoters, recruiting RNA
polymerase transcriptional machinery
What causes p53 conformational changes?
Post-translational modifications
Examples of post translational modifications
Modifications of serines and threonines (e.g. phosphorylation)
Modifications of lysines and arganines (e.g. methylation, ubiquitylation)
What do post translational modifications regulate?
Promoter transcriptional activity
What transfers ubiquitin to p53 to inactivate it?
E2
What are some hotspot p53 mutation targets?
amino acids in contact with DNA
conformation of p53
specificity and affinity of p53 for its DNA-response element and the RNA-polymerase II transcriptional machinery
Mutated p53
Can keep some functions
How can viruses inactivate p53
Inactivating interaction
Ubiquitination-induced protein
degradation
Dysregulated splicing and translation of p53
mRNA (p53 isoforms)
BCL2
Apoptosis
PD1
Immune cell death
acetylation
binding to p53RE
