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.
Mesh Terms:
Culture Media, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, DNA-Binding Proteins, Fungal Proteins, Gene Expression Regulation, Fungal, Glucose, HSP70 Heat-Shock Proteins, Mutagenesis, Protein Processing, Post-Translational, Ribonucleases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Transcription Factors, ras Proteins
Mol. Microbiol.
Date: Feb. 01, 2002
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