Comparative computational and experimental analyses of some natural small molecules to restore transcriptional activation function of p53 in cancer cells harbouring wild type and p53^Ser46 mutant.

ABSTRACT: Genetic mutations in p53 are frequently associated with many types of cancers that affect its stability and activity through multiple ways. The Ser46 residue present in the transactivation domain2 (TAD2) domain of p53 undergoes phosphorylation that blocks its degradation by MDM2 and leads to cell cycle arrest/apoptosis/necrosis upon intrinsic or extrinsic stresses. On the other hand, unphosphorylated p53 mutants escape cell arrest or death triggered by these molecular signaling axes and lead to carcinogenesis. Phosphorylation of Ser in the TAD2 domain of p53 mediates its interactions with transcription factor p62, yielding transcriptional activation of downstream pro-apoptotic genes. The p53 phosphorylation causes string-like elongated conformation that increases its binding affinity with

SUBMITTER: Shefrin S 

PROVIDER: S-EPMC9507986 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature