Nucleophosmin1 is a negative regulator of the small GTPase Rac1

PLoS One. 2013 Jul 16;8(7):e68477. doi: 10.1371/journal.pone.0068477. Print 2013.

Abstract

The Rac1 GTPase is a critical regulator of cytoskeletal dynamics and controls many biological processes, such as cell migration, cell-cell contacts, cellular growth and cell division. These complex processes are controlled by Rac1 signaling through effector proteins. We have previously identified several effector proteins of Rac1 that also act as Rac1 regulatory proteins, including caveolin-1 and PACSIN2. Here, we report that Rac1 interacts through its C-terminus with nucleophosmin1 (NPM1), a multifunctional nucleo-cytoplasmic shuttling protein with oncogenic properties. We show that Rac1 controls NPM1 subcellular localization. In cells expressing active Rac1, NPM1 translocates from the nucleus to the cytoplasm. In addition, Rac1 regulates the localization of the phosphorylated pool of NPM1 as this pool translocated from the nucleus to the cytosol in cells expressing activated Rac1. Conversely, we found that expression of NPM1 limits Rac1 GTP loading and cell spreading. In conclusion, this study identifies NPM1 as a novel, negative regulator of Rac1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cytoplasm / metabolism
  • HeLa Cells
  • Humans
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Nucleophosmin
  • Nucleoplasmins / genetics
  • Nucleoplasmins / metabolism*
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism*

Substances

  • NPM1 protein, human
  • Nucleoplasmins
  • Nucleophosmin
  • rac1 GTP-Binding Protein

Grants and funding

YZ was funded by the Lansteiner Foundation for Blood Transfusion Research (LSBR) grant no. 0630. AvS, PBvH and PLH were funded by Sanquin. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.