A nuclear phosphoinositide kinase complex regulates p53.

ABSTRACT: The tumour suppressor p53 (encoded by TP53) protects the genome against cellular stress and is frequently mutated in cancer. Mutant p53 acquires gain-of-function oncogenic activities that are dependent on its enhanced stability. However, the mechanisms by which nuclear p53 is stabilized are poorly understood. Here, we demonstrate that the stability of stress-induced wild-type and mutant p53 is regulated by the type I phosphatidylinositol phosphate kinase (PIPKI-α (also known as PIP5K1A)) and its product phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P₂). Nuclear PIPKI-α binds to p53 upon stress, resulting in the production and association of PtdIns(4,5)P₂ with p53. PtdIns(4,5)P₂ binding promotes the interaction between p53 and the small heat shock protei

SUBMITTER: Choi S 

PROVIDER: S-EPMC7017954 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature