Saccharomyces cerevisiae Ccr4-not complex contributes to the control of Msn2p-dependent transcription by the Ras/cAMP pathway.
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.
Lenssen
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Department Biochimie Médicale, CMU, 1 rue Michel Servet, 1211 Genève 4, Switzerland. CEA Saclay, France.
Oberholzer
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Labarre
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De Virgilio
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Collart
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D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D016296:Mutagenesis; D011499:Protein Processing, Post-Translational; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
D003470:Culture Media; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; C081935:MSN2 protein, S cerevisiae; C081937:MSN4 protein, S cerevisiae; C111175:NOT5 protein, S cerevisiae; C090869:SSA3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C078657:CCR4 protein, S cerevisiae; D012260:Ribonucleases; D018631:ras Proteins; D005947:Glucose