Awakening the "guardian of genome": reactivation of mutant p53.

Abstract

The role of tumor suppressor protein p53 is undeniable in the suppression of cancer upon oncogenic stress. It induces diverse conditions such as cell-cycle arrest, cell death, and senescence to protect the cell from carcinogenesis. The rate of mutations in p53 gene nearly accounts for 50% of the human cancers. Upon mutations, the conformation gets altered and becomes non-native. Mutant p53 displays long half-life and accumulates in the nucleus and interacts with oncoproteins to promote carcinogenesis and these interactions present a formidable challenge for clinicians in therapy of the disease. Variety of approaches have been developed, through which native-like function of p53 can be restored, such as restoration of the native-like structure of p53, activating the p53 family members, etc. Modern scientific techniques have led to the discovery of a variety of molecules to reactivate mutant p53 and restore its transcriptional activity. These compounds include small molecules, various peptides, and phytochemicals. In this review article, we comprehensively discuss these molecules to reactivate mutant p53 to restore the normal function with a particular focus on molecular mechanisms.