This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Arévalo-Rodríguez, M.
Right arrow Articles by Heitman, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arévalo-Rodríguez, M.
Right arrow Articles by Heitman, J.

Next Article 

Eukaryotic Cell, January 2005, p. 17-29, Vol. 4, No. 1
1535-9778/05/$08.00+0     doi:10.1128/EC.4.1.17-29.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cyclophilin A Is Localized to the Nucleus and Controls Meiosis in Saccharomyces cerevisiae{dagger}

Miguel Arévalo-Rodríguez{ddagger} and Joseph Heitman*

Departments of Molecular Genetics and Microbiology, Pharmacology and Cancer Biology, and Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina

Received 17 June 2004/ Accepted 15 October 2004

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.


* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, Box 3546, 322 CARL Bldg., Research Dr., Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-2824. Fax: (919) 684-5458. E-mail: heitm001{at}duke.edu.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

{ddagger} Present address: BIOMEDAL Centro Andaluz de Biologiía del Desarrollo, Universidad Pablo de Olavide, 41013 Seville, Spain.


Eukaryotic Cell, January 2005, p. 17-29, Vol. 4, No. 1
1535-9778/05/$08.00+0     doi:10.1128/EC.4.1.17-29.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Stie, J., Fox, D. (2008). Calcineurin Regulation in Fungi and Beyond. Eukaryot Cell 7: 177-186 [Full Text]  
  • Torgan, C. E., Daniels, M. P. (2006). Calcineurin Localization in Skeletal Muscle Offers Insights into Potential New Targets. J. Histochem. Cytochem. 54: 119-128 [Abstract] [Full Text]  
  • Harashima, T., Heitman, J. (2005). G{alpha} Subunit Gpa2 Recruits Kelch Repeat Subunits That Inhibit Receptor-G Protein Coupling during cAMP-induced Dimorphic Transitions in Saccharomyces cerevisiae. Mol. Biol. Cell 16: 4557-4571 [Abstract] [Full Text]  
  • Colgan, J., Asmal, M., Yu, B., Luban, J. (2005). Cyclophilin A-Deficient Mice Are Resistant to Immunosuppression by Cyclosporine. J. Immunol. 174: 6030-6038 [Abstract] [Full Text]  
  • Coaker, G., Falick, A., Staskawicz, B. (2005). Activation of a Phytopathogenic Bacterial Effector Protein by a Eukaryotic Cyclophilin. Science 308: 548-550 [Abstract] [Full Text]