Cellular tumor antigen p53 (TP53) (TP53)

Cellular tumor antigen p53, frequently called the guardian of the genome, is a pivotal transcription factor that orchestrates cellular responses to various stress signals, including DNA damage, hypoxia, and oncogene activation (UniProt P04637; NCBI Gene 7157). By regulating the expression of downstream genes like p21 and BAX, it induces cell cycle arrest, DNA repair, or apoptosis to maintain genomic integrity (Kastenhuber & Lowe, Cell 2017). TP53 is the most frequently mutated gene in human cancer, with alterations found in over 50% of all tumors, often leading to loss of tumor-suppressive capacity and sometimes gaining oncogenic functions (Donehower et al., Nature Reviews Cancer 2019). Therapeutic interventions focus on two main strategies: stabilizing wild-type p53 by inhibiting its negative regulator MDM2, and using small molecules to restore the functional conformation of mutant p53 proteins (ClinicalTrials.gov). While promising, these therapies face challenges such as dose-limiting hematological toxicities and the inherent complexity of targeting a protein that lacks traditional small-molecule binding pockets (Stegh, Expert Opin. Ther. Targets 2012).

Other names

Tumor protein p53p53Antigen NY-CO-13Phosphoprotein p53Transformation-related protein 53

Inhibition of the MDM2-p53 or MDMX-p53 interaction to prevent p53 degradation and restore its tumor-suppressive function; covalent binding to mutant p53 proteins to promote refolding into a functional wild-type-like conformation and restore transcriptional activity.