Identification and characterization of a highly conserved calcineurin binding protein, CBP1/calcipressin, in Cryptococcus neoformans.
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.
Görlach
J
J
Departments of Genetics, Medicine, Microbiology, Pharmacology and Cancer Biology, and The Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Fox
D S
DS
Cutler
N S
NS
Cox
G M
GM
Perfect
J R
JR
Heitman
J
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D019703:Calcineurin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D020134:Catalytic Domain; D017124:Conserved Sequence / Q000235:genetics; D003455:Cryptococcus neoformans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020104:Immunophilins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D022021:Tacrolimus Binding Proteins; D020798:Two-Hybrid System Techniques; D014774:Virulence / Q000235:genetics
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C064042:CBF1 protein, S cerevisiae; D065095:Calcineurin Inhibitors; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D019703:Calcineurin; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins