The p53 protein is a crucial tumor suppressor encoded by the TP53 gene, named for its molecular weight of approximately 53 kilodaltons. Known as the "guardian of the genome," p53 is activated in response to cellular stress (such as DNA damage, hypoxia, or oncogene activation) and regulates the transcription of downstream target genes. This leads to cell cycle arrest, DNA repair, apoptosis, or senescence, thereby maintaining genomic stability and preventing tumorigenesis. Loss of p53 function (e.g., mutation or degradation) is associated with over 50% of human cancers, and mutant p53 may also acquire oncogenic properties. Its activity is primarily negatively regulated by E3 ubiquitin ligases like MDM2, which maintain low p53 levels via ubiquitin-mediated degradation. Beyond tumor suppression, p53 is involved in metabolic regulation, immune responses, and other processes, making it a key therapeutic target in cancer. Current p53-targeted strategies include restoring mutant p53 function, inhibiting MDM2, and exploiting p53-dependent pathways.
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