Reduced levels of Dusp3/Vhr phosphatase impair normal spindle bipolarity in an Erk1/2 activity-dependent manner

FEBS Lett. 2016 Aug;590(16):2757-67. doi: 10.1002/1873-3468.12310. Epub 2016 Jul 30.

Abstract

Dual specificity phosphatase-3 (Dusp3/Vhr) regulates cell cycle progression by counteracting the effects of mitogen-activated protein kinases (Mapk) Erk1/2 and Jnk. Despite the known upregulation of Dusp3 at M phase in mammalian cells, its mitotic functions are poorly characterized. Here, we report that loss of Dusp3 by RNAi leads to the formation of multipolar spindles in human mitotic cancer cells in an Erk1/2-dependent manner. In the phosphatase-silenced cells, the normal bipolar spindle structure was restored by chemical inhibition of Erk1/2 and ectopic overexpression of Dusp3. We propose that at M phase Dusp3 keeps Erk1/2 activity in check to facilitate normal mitosis.

Keywords: Dusp3; Erk1/2; mitosis; multipolarity; spindle.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • Cell Polarity / genetics*
  • Dual Specificity Phosphatase 3 / biosynthesis
  • Dual Specificity Phosphatase 3 / genetics*
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Signaling System / genetics
  • Mitosis / genetics*
  • Phosphorylation
  • RNA Interference
  • Spindle Apparatus / genetics*
  • Transfection

Substances

  • MAP Kinase Kinase 4
  • DUSP3 protein, human
  • Dual Specificity Phosphatase 3