Cellular tumor antigen p53 (p53) (p53)

Cellular tumor antigen p53, commonly known as p53, is a pivotal transcription factor and tumor suppressor often referred to as the 'guardian of the genome' [Wikipedia, NIH]. It plays a central role in maintaining genomic integrity by orchestrating cellular responses to various stresses, including DNA damage, hypoxia, and oncogene activation [NIH, PubMed]. Upon activation, p53 induces downstream target genes that mediate cell cycle arrest, DNA repair, senescence, or apoptosis, thereby preventing the proliferation of damaged or transformed cells [NIH, UniProt]. Mutations in the TP53 gene are the most frequent genetic alterations in human cancer, occurring in more than 50% of all cases and leading to the loss of its protective functions or the acquisition of oncogenic properties [NIH, MDPI]. Therapeutic efforts are largely focused on two strategies: small molecules that reactivate mutant p53 by restoring its native conformation and inhibitors of the MDM2-p53 interaction that stabilize wild-type p53 in tumors where the gene remains intact [NIH, PubMed]. Despite its high prevalence in disease, p53 has historically been considered 'undruggable' due to its lack of traditional small-molecule binding pockets, though several candidates are currently in clinical development [NIH, MDPI].

Other names

Tumor protein p53TP53Transformation-related protein 53TRP53Tumor suppressor p53BCC7LFS1BMFS5

Drugs targeting p53 primarily work by either restoring the wild-type conformation and transcriptional activity of mutant p53 proteins or by inhibiting the interaction between wild-type p53 and its negative regulator MDM2, thereby preventing p53 degradation and increasing its cellular levels to induce tumor suppression [NIH, MDPI].