Cellular tumor antigen p53 (mutant form) (mutp53)

The mutant p53 protein arises from mutations in the TP53 gene, which is the most frequently altered gene in human cancer, occurring in approximately 50% of all cases (Surget et al., 2013, PMID: 24025503). While wild-type p53 functions as a critical tumor suppressor by regulating DNA repair, cell cycle arrest, and apoptosis, mutant forms often lose these protective functions and may exert dominant-negative effects over any remaining wild-type protein (Muller & Vousden, 2013, PMID: 23348450). Furthermore, many missense mutations confer 'gain-of-function' (GOF) properties that actively promote tumor progression, metastasis, and chemoresistance (Yue et al., 2017, PMID: 28819242). Therapeutic strategies targeting mutant p53 focus on small molecules that can refold the misfolded protein into a functional wild-type-like conformation or promote the degradation of the accumulated mutant protein (Bykov et al., 2018, PMID: 29348552). Recent clinical efforts, such as those involving APR-246 and allele-specific inhibitors like PC14586 (targeting the Y220C mutation), represent a shift toward precision oncology by directly addressing the structural defects of specific p53 mutants (Duffy et al., 2022, PMID: 35145234).

Other names

Tumor protein p53TP53Antigen NY-CO-13Phosphoprotein p53Transformation-related protein 53

Pharmacological restoration of wild-type conformation and transcriptional activity; induction of mutant protein degradation; inhibition of gain-of-function protein-protein interactions; induction of ferroptosis.