A dual role for PP1 in shaping the Msn2-dependent transcriptional response to glucose starvation

EMBO J. 2005 Dec 7;24(23):4115-23. doi: 10.1038/sj.emboj.7600871. Epub 2005 Nov 10.

Abstract

In yeast, glucose depletion elicits a quick response in the transcription of stress-related genes. The main transcriptional activator that orchestrates this response is Msn2, whose nuclear localization and DNA binding are negatively controlled by the cAMP-dependent protein kinase (PKA). Msn2 activation by sudden glucose depletion correlates with a fast but transient decrease in phosphorylation of several sites in its nuclear localization signal (NLS). Here we show that protein phosphatase 1 (PP1) is the direct antagonist of PKA-dependent phosphorylation at the Msn2 nuclear import domain and therefore a potential mediator of glucose starvation signals that target this transcription factor. Apart from PKA, the protein kinase Snf1 can also directly modify one of the Msn2 phosphorylation sites (S582) and thereby repress Msn2 function. Consequently, in snf1 mutants, rephosphorylation of the NLS happens to be much slower during prolonged starvation. Thus, a second, Reg1-dependent form of PP1 indirectly influences Msn2 functionality by modulating Snf1 kinase activation and repression. Different activities of PP1 are therefore involved in shaping induction and adaptation of the transcriptional stress response during acute glucose starvation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / physiology*
  • Glucose / deficiency*
  • Nuclear Localization Signals / chemistry
  • Nuclear Localization Signals / metabolism
  • Oxidative Stress / physiology
  • Phosphoprotein Phosphatases / physiology*
  • Phosphorylation
  • Protein Phosphatase 1
  • Protein Serine-Threonine Kinases / chemistry
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / physiology*
  • Serine / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / physiology*

Substances

  • DNA-Binding Proteins
  • MSN2 protein, S cerevisiae
  • Nuclear Localization Signals
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Serine
  • SNF1-related protein kinases
  • Protein Serine-Threonine Kinases
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1
  • Glucose