Targeting PSAT1 to mitigate metastasis in tumors with p53-72Pro variant.

ABSTRACT: The single-nucleotide polymorphism (SNP) of p53, in particular the codon 72 variants, has recently been implicated as a critical regulator in tumor progression. However, the underlying mechanism remains elusive. Here we found that cancer cells carrying codon 72-Pro variant of p53 showed impaired metastatic potential upon serine supplementation. Proteome-wide mapping of p53-interacting proteins uncovered a specific interaction of the codon 72 proline variant (but not p53^72R) with phosphoserine aminotransferase 1 (PSAT1). Interestingly, p53^72P-PSAT1 interaction resulted in dissociation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) that otherwise bound to p53^72P, leading to subsequent nuclear translocation of PGC-1α and activation of

SUBMITTER: Jiang J 

PROVIDER: S-EPMC9929071 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature