Chi attiva P53?
Nelle cellule normali P53 è solitamente inattiva, legata alla proteina MDM2 che inibisce la proteina e ne promuove la degradazione funzionando come una ligasi dell’ubiquitina. Anche gli oncogeni stimolano l’attivazione di P53 mediante la proteina p14ARF.
Come agisce p53?
La p53 attiva la trascrizione del gene codificante p21, un inibitore delle chinasi dipendenti dalla ciclina (Cdk), che si lega a molteplici complessi Cdk-ciclina e blocca la fosforilazione delle proteine necessarie alle diverse fasi del ciclo cellulare.
What is the pathophysiology of p53-mediated protein degradation?
The degradation of the p53 protein is associated with binding of MDM2. In a negative feedback loop, MDM2 itself is induced by the p53 protein. Mutant p53 proteins often fail to induce MDM2, causing p53 to accumulate at very high levels. Moreover, the mutant p53 protein itself can inhibit normal p53 protein levels.
What is the function of p53?
Wild-type p53 is a labile protein, comprising folded and unstructured regions that function in a synergistic manner. Function DNA damage and repair . p53 plays a role in regulation or progression through the cell cycle, apoptosis, and genomic stability by means of several mechanisms:
What happens when p53 is deleted?
More than 50 percent of human tumors contain a mutation or deletion of the TP53 gene. Loss of p53 creates genomic instability that most often results in an aneuploidy phenotype. Increasing the amount of p53 may seem a solution for treatment of tumors or prevention of their spreading.
What is the role of p53 gene mutations in colorectal carcinoma?
“Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas”. Science. 244 (4901): 217–21. Bibcode: 1989Sci…244..217B. doi: 10.1126/science.2649981. PMID 2649981. ^ Finlay CA, Hinds PW, Levine AJ (June 1989). “The p53 proto-oncogene can act as a suppressor of transformation”.