What happens when p53 is phosphorylated?
What happens when p53 is phosphorylated?
Following stress, p53 is phosphorylated at multiple residues, thereby modifying its biochemical functions required for increased activity as a transcription factor. The biochemical functions include sequence-specific DNA binding and protein-protein interactions.
How does p53 bind the DNA?
p53 activates or inhibits transcription by binding to specific DNA target sequences. The p53 binding site consists of two half-sites 5´-PuPuPuC(A/T)(T/A)GPyPyPy-3´, linked by a 0-13 nucleotide spacer.
What happens when p53 binds to damaged DNA?
Activation of p53 in response to DNA damage is associated with a rapid increase in its levels and with an increased ability of p53 to bind DNA and mediate transcriptional activation. This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair.
Does p53 need to be phosphorylated?
Although phosphorylation of p53 does not appear to be essential for p53 function, several studies have suggested that phosphorylation of p53 plays an important role in regulating p53 activities such as stability and DNA binding.
How is p53 inactivated?
The p53 protein is such a powerful tumor suppressor that it is inactivated in almost every tumor, through either mutations in the TP53 gene or deregulation of its associated pathways.
Does p53 bind to DNA polymerase?
Furthermore, it binds to DNA polymerase α-primase (pol-prim) and to the eukaryotic single-stranded DNA-binding protein, replication protein A (RPA) (28,29). In addition, it was shown that p53 contains an intrinsic 3′–5′-exonuclease activity, which might play a role in DNA replication or repair (30–32).
What is a p53 mutation?
Mutations (changes) in the p53 gene may cause cancer cells to grow and spread in the body. These changes have been found in a genetic condition called Li-Fraumeni syndrome and in many types of cancer. The p53 gene is a type of tumor suppressor gene. Also called TP53 gene and tumor protein p53 gene.
What activates p53 gene?
The tumour suppressor protein p53 is stabilised and activated in response to ionising radiation. This is known to depend on the kinase ATM; recent results suggest ATM acts via the downstream kinase Chk2/hCds1, which stabilises p53 at least in part by direct phosphorylation of residue serine 20.
