Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains.

Breuder, T; Hemenway, C S; Movva, N R; Cardenas, M E; Heitman, J

doi:10.1073/pnas.91.12.5372

Cited by 135Signaling Pathways in DiseaseFungal and yeast genetics researchBacterial Genetics and Biotechnology

Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains.

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Breuder, T, Hemenway, C S, Movva, N R, Cardenas, M E, Heitman, J·1994·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.91.12.5372PMC PMC43997

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Abstract

The immunophilin-immunosuppressant complexes cyclophilin-cyclosporin A (CsA) and FKBP12-FK506 inhibit the phosphatase calcineurin to block T-cell activation. Although cyclophilin A, FKBP12, and calcineurin are highly conserved from yeast to man, none had previously been shown to be essential for viability. We find that CsA-sensitive yeast strains are FK506 hypersensitive and demonstrate that calcineurin is required for viability in these strains. Mutants lacking cyclophilin A or FKBP12 are resistant to CsA or FK506, respectively. Thus, both the immunosuppressive and the antifungal actions of CsA and FK506 result from calcineurin inhibition by immunophilin-drug complexes. In yeast strains in which calcineurin is not essential, calcineurin inhibition or mutation of calcineurin confers hypersensitivity to LiCl or NaCl, suggesting that calcineurin regulates cation transport.

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Authors: Breuder, T., Hemenway, C. S., Movva, N. R., Cardenas, M. E., & Heitman, J.
Affiliations: Howard Hughes Medical Institute (US)
ORCID: Hemenway, C S
Heitman, J
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1994-06-07
Volume: 91
Issue: 12
Pages: 5372-5376
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.91.12.5372
PMC: PMC43997
OpenAlex: W1967407965
Cited by: 135
References: 45
Citations by year: 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 9 · 2016: 3 · 2015: 1 · 2014: 3 · 2012: 1
FWCI: 3.80
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
National Institute of Environmental Health Sciences (ES 07031, T32ES007031)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords: calcineurin, cyclosporine, FK506, immunophilins, cyclophilin A, FKBP12, yeast viability, cation transport, antifungal activity, T cell activation
MeSH terms: Amino Acid Isomerases, Base Sequence, Calmodulin-Binding Proteins, Carrier Proteins, Drug Resistance, Microbial, Lithium, Molecular Sequence Data, Neomycin, Phosphoprotein Phosphatases, Saccharomyces cerevisiae, Sodium, Tacrolimus, Cyclosporine, DNA Primers, Peptidylprolyl Isomerase, Calcineurin

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Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains.

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