Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell survival at high osmolarity

EMBO J. 2006 Jun 7;25(11):2338-46. doi: 10.1038/sj.emboj.7601095. Epub 2006 May 11.

Abstract

Control of cell cycle progression by stress-activated protein kinases (SAPKs) is essential for cell adaptation to extracellular stimuli. Exposure of yeast to osmostress leads to activation of the Hog1 SAPK, which controls cell cycle at G1 by the targeting of Sic1. Here, we show that survival to osmostress also requires regulation of G2 progression. Activated Hog1 interacts and directly phosphorylates a residue within the Hsl7-docking site of the Hsl1 checkpoint kinase, which results in delocalization of Hsl7 from the septin ring and leads to Swe1 accumulation. Upon Hog1 activation, cells containing a nonphosphorylatable Hsl1 by Hog1 are unable to promote Hsl7 delocalization, fail to arrest at G2 and become sensitive to osmostress. Together, we present a novel mechanism that regulates the Hsl1-Hsl7 complex to integrate stress signals to mediate cell cycle arrest and, demonstrate that a single MAPK coordinately modulates different cell cycle checkpoints to improve cell survival upon stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Survival*
  • Enzyme Activation
  • Enzyme Stability
  • G2 Phase / physiology*
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Osmolar Concentration
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein-Arginine N-Methyltransferases
  • Protein-Serine-Threonine Kinases
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Two-Hybrid System Techniques

Substances

  • Cell Cycle Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein-Arginine N-Methyltransferases
  • HSL7 protein, S cerevisiae
  • Protein Kinases
  • SWE1 protein, S cerevisiae
  • Protein-Tyrosine Kinases
  • HSL1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • HOG1 protein, S cerevisiae
  • Mitogen-Activated Protein Kinases