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Sensitivity to cyclosporin A is mediated by cyclophilin in Neurospora crassa and Saccharomyces cerevisiae

Nature volume 342, pages 953–955 (1989)Cite this article

Abstract

CYCLOSPORIN A, a cyclic fungal undecapeptide produced by Tolypocladium inflatum, is a potent immunosuppressive drug originally isolated as an antifungal antibiotic1,2. Cyclosporin A (CsA) is widely used in humans to prevent rejection of transplanted organs such as kidney, heart, bone marrow and liver3. The biochemical basis of CsA action is not known: its primary cellular target has been suggested to be calmodulin4,5, the prolactin receptor6,7 or cyclophilin, a CsA-binding protein originally isolated from the cytosol of bovine thymocytes8–10. Cyclophilin has been shown to be a highly conserved protein present in all eukaryotic cells tested11–15 and to be identical16,17 to peptidyl-prolyl ds-trans isomerase18,19, a novel type of enzyme20 that accelerates the slow refolding phase of certain proteins in vitro21,22. We demonstrate that in the lower eukaryotes N. crassa and S. cerevisiae, cyclophilin mediates the cytotoxic CsA effect. In CsA-resistant mutants of both organisms, the cyclophilin protein is either lost completely or, if present, has lost its ability to bind CsA.

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Author information

Authors and Affiliations

  1. Institut für Physiologische Chemie der Universität München, Goethestrasse 33, D–8000, München, 2, FRG

    Maximilian Tropschug & Walter Neupert

  2. Institut für Angewandte Genetik der Universität Hannover, Herrenhäuserstrasse 2, D-3000, Hannover, 21, FRG

    Ilse B. Bartheimess

Authors
  1. Maximilian Tropschug
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  2. Ilse B. Bartheimess
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  3. Walter Neupert
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Tropschug, M., Bartheimess, I. & Neupert, W. Sensitivity to cyclosporin A is mediated by cyclophilin in Neurospora crassa and Saccharomyces cerevisiae. Nature 342, 953–955 (1989). https://doi.org/10.1038/342953a0

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