Abstract
Three families of prolyl isomerases have been identified: cyclophilins, FK506-binding proteins (FKBPs) and parvulins. All 12 cyclophilins and FKBPs are dispensable for growth in yeast, whereas the one parvulin homolog, Ess1, is essential. We report here that cyclophilin A becomes essential when Ess1 function is compromised. We also show that overexpression of cyclophilin A suppresses ess1 conditional and null mutations, and that cyclophilin A enzymatic activity is required for suppression. These results indicate that cyclophilin A and Ess1 function in parallel pathways and act on common targets by a mechanism that requires prolyl isomerization. Using genetic and biochemical approaches, we found that one of these targets is the Sin3-Rpd3 histone deacetylase complex, and that cyclophilin A increases and Ess1 decreases disruption of gene silencing by this complex. We show that conditions that favor acetylation over deacetylation suppress ess1 mutations. Our findings support a model in which Ess1 and cyclophilin A modulate the activity of the Sin3-Rpd3 complex, and excess histone deacetylation causes mitotic arrest in ess1 mutants.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylation
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DNA, Ribosomal / genetics
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DNA-Binding Proteins / metabolism
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Enzyme Stability
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Gene Expression Regulation, Enzymologic
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Gene Expression Regulation, Fungal
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Gene Silencing*
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Genes, Fungal / genetics
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Genes, Lethal / genetics
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Histone Deacetylase Inhibitors
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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Immunophilins / genetics
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Immunophilins / physiology
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Mitosis
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Models, Biological
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NIMA-Interacting Peptidylprolyl Isomerase
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Peptidylprolyl Isomerase / genetics
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Peptidylprolyl Isomerase / metabolism*
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RNA Polymerase II / metabolism
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Repressor Proteins*
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Saccharomyces cerevisiae / enzymology*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae Proteins*
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Suppression, Genetic
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Tacrolimus Binding Proteins
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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CTH1 protein, S cerevisiae
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DNA, Ribosomal
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DNA-Binding Proteins
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Histone Deacetylase Inhibitors
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NIMA-Interacting Peptidylprolyl Isomerase
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Repressor Proteins
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SIN3 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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RNA Polymerase II
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RPD3 protein, S cerevisiae
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Histone Deacetylases
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SAP30 protein, S cerevisiae
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Tacrolimus Binding Proteins
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ESS1 protein, S cerevisiae
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Immunophilins
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Peptidylprolyl Isomerase