Hog1 activation delays mitotic exit via phosphorylation of Net1

Proc Natl Acad Sci U S A. 2020 Apr 21;117(16):8924-8933. doi: 10.1073/pnas.1918308117. Epub 2020 Apr 7.

Abstract

Adaptation to environmental changes is crucial for cell fitness. In Saccharomyces cerevisiae, variations in external osmolarity trigger the activation of the stress-activated protein kinase Hog1 (high-osmolarity glycerol 1), which regulates gene expression, metabolism, and cell-cycle progression. The activation of this kinase leads to the regulation of G1, S, and G2 phases of the cell cycle to prevent genome instability and promote cell survival. Here we show that Hog1 delays mitotic exit when cells are stressed during metaphase. Hog1 phosphorylates the nucleolar protein Net1, altering its affinity for the phosphatase Cdc14, whose activity is essential for mitotic exit and completion of the cell cycle. The untimely release of Cdc14 from the nucleolus upon activation of Hog1 is linked to a defect in ribosomal DNA (rDNA) and telomere segregation, and it ultimately delays cell division. A mutant of Net1 that cannot be phosphorylated by Hog1 displays reduced viability upon osmostress. Thus, Hog1 contributes to maximizing cell survival upon stress by regulating mitotic exit.

Keywords: MAPK; Net1; cell cycle; mitosis; osmostress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromosome Segregation / physiology*
  • DNA, Ribosomal / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mitosis / physiology*
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Osmotic Pressure / physiology
  • Phosphorylation / genetics
  • Protein Tyrosine Phosphatases / metabolism
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Telomere Homeostasis / physiology

Substances

  • CDC14 protein, S cerevisiae
  • Cell Cycle Proteins
  • DNA, Ribosomal
  • Net1 protein, S cerevisiae
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • HOG1 protein, S cerevisiae
  • Mitogen-Activated Protein Kinases
  • Protein Tyrosine Phosphatases