Tumor protein p53 R248Q mutant (TP53 R248Q)

TP53 R248Q mutation is a hotspot missense mutation in the DNA-binding domain of the tumor protein p53, replacing arginine at codon 248 with glutamine. This mutation impairs the ability of p53 to bind its canonical DNA consensus sequence, disabling its normal tumor suppressive activities (cell cycle arrest, apoptosis, senescence). In many cancers, the R248Q mutant protein acquires gain-of-function properties (promoting invasion, altering cell adhesion, supporting tumor progression). R248Q is classified as a DNA-contact mutation, distinctly impairing DNA recognition but often preserving overall protein conformation, and is one of the most frequently observed p53 mutant alleles in human tumors. Therapeutic strategies are under active development to target tumors that depend on mutant p53, including agents that restore wild-type activity or specifically degrade the mutant protein.

Other names

p53 R248Qmutant p53 R248QTP53 hotspot mutation R248Qp53 DNA contact mutant

Restoration of wild-type p53 function; Targeted degradation of mutant p53; Synthetic lethality with mutant p53; Inhibition of mutant p53 gain-of-function activities; Re-sensitization of cancer cells to apoptosis