Cyclophilin A is localized to the nucleus and controls meiosis in Saccharomyces cerevisiae

Eukaryot Cell. 2005 Jan;4(1):17-29. doi: 10.1128/EC.4.1.17-29.2005.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Northern
  • Blotting, Western
  • Cell Nucleus / metabolism*
  • Cyclophilin A / biosynthesis*
  • Cytoplasm / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / metabolism
  • Histone Deacetylases / metabolism
  • Immunoprecipitation
  • Meiosis*
  • Models, Biological
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Oligonucleotides / chemistry
  • Peptidylprolyl Isomerase / metabolism
  • Peptidylprolyl Isomerase / physiology
  • Plasmids / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction
  • Temperature
  • Time Factors
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • NIMA-Interacting Peptidylprolyl Isomerase
  • Oligonucleotides
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • SIN3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Green Fluorescent Proteins
  • RPD3 protein, S cerevisiae
  • Histone Deacetylases
  • Cyclophilin A
  • ESS1 protein, S cerevisiae
  • PIN1 protein, human
  • Peptidylprolyl Isomerase