Tumor protein p53 R175H mutant (TP53 R175H)

The TP53 R175H mutation is a missense mutation within the tumor protein p53 (TP53) gene, resulting in the substitution of arginine with histidine at position 175. This residue sits in the DNA-binding domain, specifically at a critical zinc-binding site, and mutations here destabilize p53’s conformation, leading to loss of DNA-binding and canonical tumor suppressor function[1][2][7]. Unlike wild-type p53, which acts as a transcription factor regulating cell cycle arrest, apoptosis, DNA repair, and senescence, the R175H mutant is classified as a structural or conformational mutant: it not only loses its suppressive functions but can also exert dominant-negative and gain-of-function (GOF) oncogenic effects, promoting drug resistance, tumor progression, and aggregation that interferes with wild-type p53, p63, and p73[1][4]. The R175H mutation is among the most common "hotspot" p53 mutations in human cancer[1][4]. Current therapeutic strategies include small molecules or peptides that stabilize the correct conformation of mutant p53 or restore its wild-type DNA binding and transcriptional activity[6]. The TP53 R175H mutation is frequently used as a biomarker for patient stratification in cancer research and clinical trials.

Other names

p53 R175Hmutant p53 R175HTP53 Arg175HisR175H mutant of p53

Allosteric reactivation of mutant p53 (conformational stabilization); Promoting refolding to wild-type-like conformation; Induction of apoptosis by restoring transcriptional activation of target genes (e.g., p21, PUMA, NOXA); Inhibition of protein aggregation; Degradation targeting (proteolysis-inducing agents in development)