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. 1994 Jun 7;91(12):5372-6.
doi: 10.1073/pnas.91.12.5372.

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

T Breuder  1 , C S Hemenway, N R Movva, M E Cardenas, J Heitman
Affiliations

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

T Breuder et al. Proc Natl Acad Sci U S A. .

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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References

    1. Mol Gen Genet. 1984;193(3):557-60 - PubMed
    1. Nature. 1992 Dec 17;360(6405):682-4 - PubMed
    1. Mol Gen Genet. 1984;197(2):345-6 - PubMed
    1. Cell. 1985 Sep;42(2):479-88 - PubMed
    1. Chem Pharm Bull (Tokyo). 1985 Apr;33(4):1576-82 - PubMed

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