Saccharomyces cerevisiae Ccr4-not complex contributes to the control of Msn2p-dependent transcription by the Ras/cAMP pathway

Mol Microbiol. 2002 Feb;43(4):1023-37. doi: 10.1046/j.1365-2958.2002.02799.x.


The Ccr4-Not complex is a global regulator of transcription that affects genes positively and negatively and is thought to modulate the activity of TFIID. In the present work, we provide evidence that the Ccr4-Not complex may contribute to transcriptional regulation by the Ras/cAMP pathway. Several observations support this model. First, Msn2/4p-dependent transcription, which is known to be under negative control of cAMP-dependent protein kinase (PKA), is derepressed in all ccr4-not mutants. This phenotype is paralleled by specific post-translational modification defects of Msn2p in ccr4-not mutants relative to wild-type cells. Secondly, mutations in various NOT genes result in a synthetic temperature-sensitive growth defect when combined with mutations that compromise cells for PKA activity and at least partially suppress the effects of both a dominant-active RAS2Val-19 allele and loss of Rim15p. Thirdly, Not3p and Not5p, which are modified and subsequently degraded by stress signals that also lead to increased Msn2/4p-dependent activity, show a specific two-hybrid interaction with Tpk2p. Together, our results suggest that the Ccr4-Not complex may function as an effector of the Ras/cAMP pathway that contributes to repress basal, stress- and starvation-induced transcription by Msn2/4p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Culture Media
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression Regulation, Fungal*
  • Glucose / pharmacology
  • HSP70 Heat-Shock Proteins / genetics
  • Mutagenesis
  • Protein Processing, Post-Translational
  • Ribonucleases / genetics
  • Ribonucleases / metabolism*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • ras Proteins / metabolism*


  • Culture Media
  • DNA-Binding Proteins
  • Fungal Proteins
  • HSP70 Heat-Shock Proteins
  • MSN2 protein, S cerevisiae
  • MSN4 protein, S cerevisiae
  • NOT5 protein, S cerevisiae
  • SSA3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • CCR4 protein, S cerevisiae
  • Ribonucleases
  • ras Proteins
  • Glucose