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

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.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Breuder T,Hemenway CS,Movva NR,Cardenas ME,Heitman J

doi

10.1073/pnas.91.12.5372

subject

Has Abstract

pub_date

1994-06-07 00:00:00

pages

5372-6

issue

12

eissn

0027-8424

issn

1091-6490

journal_volume

91

pub_type

杂志文章

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