Identification and characterization of a highly conserved calcineurin binding protein, CBP1/calcipressin, in Cryptococcus neoformans
Identification and characterization of a highly conserved calcineurin binding protein, CBP1/calcipressin, in Cryptococcus neoformans
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DOI：
10.1093/emboj/19.14.3618
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发表时间：
2000-07-17
期刊：
影响因子：
11.4
通讯作者：
Heitman, J
中科院分区：
文献类型：
--
作者：
Görlach, J;Fox, DS;Heitman, J
钙调神经磷酸酶是免疫抑制剂环孢素A（cyclosporin A）和FK 506的保守作用靶点。我们利用酵母双杂交系统从新生隐球菌（Cryptococcus neoformans）中鉴定了一种新的钙调神经磷酸酶结合蛋白CBP 1。我们发现CBP 1在体外和体内都能与钙调神经磷酸酶结合，而FKBP 12-FK 506抑制CBP 1与钙调神经磷酸酶的结合。新型隐球菌cbp 1突变株在应激条件下的生长和毒力方面表现出适度的缺陷，与钙调磷酸酶突变体的表型相似，但不如钙调磷酸酶突变体严重，缺乏cbp 1同源物RCN 1的酿酒酵母突变体与钙调磷酸酶突变体一样，对锂阳离子应激敏感，CBP 1与酿酒酵母、粟酒裂殖酵母、黑腹果蝇、秀丽隐杆线虫和人类中的相关蛋白共享中心肽序列基序SPPxSPP，并且含有该基序的肽在体外改变钙调磷酸酶活性。有趣的是，人类CBP 1同源物DSCR 1由21号染色体上的唐氏综合征候选区域间隔编码，在心脏和中枢神经系统中高度表达，并且可能在心脏发育、神经突延伸和记忆中的钙调神经磷酸酶功能中发挥作用。
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.