Cyclophilin A is localized to the nucleus and controls meiosis in Saccharomyces cerevisiae.
Cyclophilin A is conserved from yeast to humans and mediates the ability of cyclosporine to perturb signal transduction cascades via inhibition of calcineurin. Cyclophilin A also catalyzes cis-trans peptidyl-prolyl isomerization during protein folding or conformational changes; however, cyclophilin A is not essential in yeast or human cells, and the true ... biological functions of this highly conserved enzyme have remained enigmatic. In Saccharomyces cerevisiae, cyclophilin A becomes essential in cells compromised for the nuclear prolyl-isomerase Ess1, and cyclophilin A physically interacts with two nuclear histone deacetylase complexes, Sin3-Rpd3 and Set3C, which both control meiosis. Here we show that cyclophilin A is localized to the nucleus in yeast cells and governs the meiotic gene program to promote efficient sporulation. The prolyl-isomerase activity of cyclophilin A is required for this meiotic function. We document that cyclophilin A physically associates with the Set3C histone deacetylase and analyze in detail the structure of this protein-protein complex. Genetic studies support a model in which cyclophilin A controls meiosis via Set3C and an additional target. Our findings reveal a novel nuclear role for cyclophilin A in governing the transcriptional program required for the vegetative to meiotic developmental switch in budding yeast.
Mesh Terms:
Blotting, Northern, Blotting, Western, Cell Nucleus, Cyclophilin A, Cytoplasm, Electrophoresis, Polyacrylamide Gel, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Histone Deacetylases, Immunoprecipitation, Meiosis, Models, Biological, Oligonucleotides, Peptidylprolyl Isomerase, Plasmids, Recombinant Fusion Proteins, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Temperature, Time Factors, Transcription Factors, Transcription, Genetic
Blotting, Northern, Blotting, Western, Cell Nucleus, Cyclophilin A, Cytoplasm, Electrophoresis, Polyacrylamide Gel, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Histone Deacetylases, Immunoprecipitation, Meiosis, Models, Biological, Oligonucleotides, Peptidylprolyl Isomerase, Plasmids, Recombinant Fusion Proteins, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Temperature, Time Factors, Transcription Factors, Transcription, Genetic
Eukaryotic Cell
Date: Jan. 01, 2005
PubMed ID: 15643056
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