Premium
Identification and characterization of a highly conserved calcineurin binding protein, CBP1/calcipressin, in Cryptococcus neoformans
Author(s) -
Görlach Jenifer,
Fox Deborah S.,
Cutler N. Shane,
Cox Gary M.,
Perfect John R.,
Heitman Joseph
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.14.3618
Subject(s) - biology , cryptococcus neoformans , calcineurin , identification (biology) , cryptococcus , computational biology , fungal protein , conserved sequence , genetics , microbiology and biotechnology , peptide sequence , gene , ecology , medicine , surgery , transplantation
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.