Nek10 mediates G2/M cell cycle arrest and MEK autoactivation in response to UV irradiation

Mol Cell Biol. 2011 Jan;31(1):30-42. doi: 10.1128/MCB.00648-10. Epub 2010 Oct 18.

Abstract

Appropriate cell cycle checkpoint control is essential for the maintenance of cell and organismal homeostasis. Members of the Nek (NIMA-related kinase) family of serine/threonine protein kinases have been implicated in the regulation of various aspects of the cell cycle. We explored the cellular functions of Nek10, a novel member of the Nek family, and demonstrate a role for Nek10 in the cellular UV response. Nek10 was required for the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling upon UV irradiation but not in response to mitogens, such as epidermal growth factor stimulation. Nek10 physically associated with Raf-1 and MEK1 in a Raf-1-dependent manner, and the formation of this complex was necessary for Nek10-mediated MEK1 activation. Nek10 did not affect the kinase activity of Raf-1 but instead promoted the autophosphorylation-dependent activation of MEK1. The appropriate maintenance of the G(2)/M checkpoint following UV irradiation required Nek10 expression and ERK1/2 activation. Taken together, our results uncover a role for Nek10 in the cellular response to UV irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Cell Cycle / physiology*
  • Cell Cycle / radiation effects*
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Division / physiology
  • Cell Division / radiation effects
  • Cell Line
  • Cell Line, Tumor
  • Cloning, Molecular
  • DNA Primers / genetics
  • Enzyme Activation / radiation effects
  • Female
  • G2 Phase / physiology
  • G2 Phase / radiation effects
  • Gene Knockdown Techniques
  • Genetic Predisposition to Disease
  • Humans
  • MAP Kinase Kinase 1 / metabolism*
  • MAP Kinase Signaling System
  • Multienzyme Complexes / metabolism
  • NIMA-Related Kinase 1
  • NIMA-Related Kinases
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-raf / metabolism
  • Ultraviolet Rays / adverse effects*

Substances

  • Cell Cycle Proteins
  • DNA Primers
  • Multienzyme Complexes
  • NEK1 protein, human
  • NIMA-Related Kinase 1
  • NIMA-Related Kinases
  • Nek10 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human