Phosphorylation of multifunctional nucleolar protein nucleophosmin (NPM1) by aurora kinase B is critical for mitotic progression

Abstract

The functional association of NPM1 with Aurora ldnases is well documented. Surprisingly, although NPM1 is a well characterized phosphoprotein, it is unknown whether it is a substrate of Aurora kinases. We have found that Aurora kinases A and B can phosphorylate NPM1 at a single serine residue, Ser125, in vitro and in vivo. Phosphorylated-S125-NPM1 (pS125-NPM1) localizes to the midbody region during late cytoldnesis where it colocalizes with Aurora B. The overexpression of mutant (S125A) NPM1 resulted in the deregulation of centrosome duplication and mitotic defects possibly due to cytokinesis failure. These data suggest that Aurora kinase B-mediated phosphorylation of NPM1 plays a critical role during mitosis, which could have wider implications in oncogenesis. Structured summary of protein interactions: Aurora A phosphorylates NPM by protein kinase assay (1,2) Aurora B phosphorylates NPM by protein kinase assay (View interaction) NPM and Aurora A colocalize by fluorescence microscopy (View interaction) NPM and Aurora B colocalize by fluorescence microscopy (View interaction) NPM binds to Aurora B by pull down (View interaction) NPM physically interacts with Aurora B by anti tag coimmunoprecipitation (1,2) (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.