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

FEBS Lett. 2014 Jun 27;588(14):2198-205. doi: 10.1016/j.febslet.2014.05.014. Epub 2014 May 21.

Abstract

The functional association of NPM1 with Aurora kinases 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 cytokinesis 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.

Keywords: Aurora kinases; Cytokinesis; Mitosis; Nucleophosmin; Phosphorylation; Serine threonine protein kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase A / chemistry
  • Aurora Kinase B / chemistry
  • Aurora Kinase B / physiology*
  • Carcinoma, Squamous Cell / enzymology
  • Cell Transformation, Neoplastic / metabolism
  • Centrosome / metabolism
  • HEK293 Cells
  • Humans
  • Mice
  • Mouth Neoplasms / enzymology
  • NIH 3T3 Cells
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Nucleophosmin
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Protein Transport
  • Telophase

Substances

  • NPM1 protein, human
  • Npm1 protein, mouse
  • Nuclear Proteins
  • Nucleophosmin
  • AURKA protein, human
  • AURKB protein, human
  • Aurora Kinase A
  • Aurora Kinase B