T95 nucleophosmin phosphorylation as a novel mediator and marker of regulated cell death in acute kidney injury.

ABSTRACT: The function of site-specific phosphorylation of nucleophosmin (NPM), an essential Bax chaperone, in stress-induced cell death is unknown. We hypothesized that NPM threonine 95 (T95) phosphorylation both signals and promotes cell death. In resting cells, NPM exclusively resides in the nucleus and T95 is nonphosphorylated. In contrast, phosphorylated T95 NPM (pNPM T95) accumulates in the cytosol after metabolic stress, in multiple human cancer cell lines following γ-radiation, and in postischemic human kidney tissue. Based on the T95 phosphorylation consensus sequence, we hypothesized that glycogen synthase kinase-3β (GSK-3β) regulates cytosolic NPM translocation by phosphorylating T95 NPM. In a cell-free system, GSK-3β phosphorylated a synthetic NPM peptide containing T95. In vitro, bidire

SUBMITTER: Wang Z 

PROVIDER: S-EPMC7509286 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature