In: Biology
What role does p53 play in mediating cell cycle arrest for cells with DNA damage? How is p53 activated?
When DNA is damaged, various protein kinases are recruited to the site of damage and initiates a signalling pathway that causes cell cycle arrest. The protein kinases cause phosphorylation of the protein p53 . Mdm2 normally binds to p53 and promotes it's ubiquitination and destruction by proteosomes. Phosphorylation of p53 blocks it's binding to mdm2 ; as a result , p53 accumulates to high levels and stimulates transcription of the genes that encodes the CKI ( CDK inhibitor Protein) p21. The p21 binds and inactivates G1/S-CDK and S-CDK complexes , arresting the cell in G1.
p53 is inactivated when it is associated with mdm2, upon DNA damage or other stresses , various pathways lead to the dissociation of the p53 and mdm2 complex, p53 becomes activated. And induced cell cycle arrest to allow either repair and survival of the cell, or apoptosis to discard the damaged cell.