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  • The EMBO Journal (2000) 19, 3618 - 3629
  • doi:10.1093/emboj/19.14.3618

Identification and characterization of a highly conserved calcineurin binding protein, CBP1/calcipressin, in Cryptococcus neoformans

Jenifer Görlach1,2, Deborah S. Fox1, N. Shane Cutler1, Gary M. Cox2,3, John R. Perfect2,3 and Joseph Heitman1,2,3,4,5,6

  1. Department of Genetics, Duke University Medical Center, Durham, NC 27710, USA
  2. Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
  3. Department of Microbiology, Duke University Medical Center, Durham, NC 27710, USA
  4. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
  5. The Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
  6. Department of Genetics, 322 CARL Building, Box 3546 Duke University Medical Center, Research Drive, Durham, NC 27710, USA

Correspondence to:

Joseph Heitman, E-mail: heitm001@duke.edu

Received 4 February 2000; Accepted 25 May 2000; Revised 24 May 2000

Calcineurin is the conserved target of the immunosuppressants cyclosporin A and FK506. Using the yeast two-hybrid system, we identified a novel calcineurin binding protein, CBP1, from the pathogenic fungus Cryptococcus neoformans. We show that CBP1 binds to calcineurin in vitro and in vivo, and FKBP12–FK506 inhibits CBP1 binding to calcineurin. Cryptococcus neoformans cbp1 mutant strains exhibit modest defects in growth under stress conditions and virulence, similar to but less severe than the phenotypes of calcineurin mutants. Saccharomyces cerevisiae mutants lacking the CBP1 homolog RCN1 are, like calcineurin mutants, sensitive to lithium cation stress. CBP1 shares a central peptide sequence motif, SPPxSPP, with related proteins in S.cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster, Caenorhabditis elegans and humans, and peptides containing this motif altered calcineurin activity in vitro. Interestingly, the human CBP1 homolog DSCR1 is encoded by the Down's syndrome candidate region interval on chromosome 21, is highly expressed in the heart and central nervous system, and may play a role in calcineurin functions in heart development, neurite extension and memory.

  • Keywords:

    • calcineurin,
    • Cryptococcus neoformans,
    • Down's syndrome,
    • pathogenic fungi,
    • protein phosphatase