The BST1 Gene of Saccharomyces cerevisiaeIs the Sphingosine-1-phosphate Lyase*
The BST1 Gene of Saccharomyces cerevisiaeIs the Sphingosine-1-phosphate Lyase*
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DOI：
10.1074/jbc.272.42.26087
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发表时间：
1997-10
期刊：
影响因子：
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通讯作者：
J. Saba;F. Nara;Alicia Bielawska;S. Garrett;Y. Hannun
中科院分区：
文献类型：
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作者：
J. Saba;F. Nara;Alicia Bielawska;S. Garrett;Y. Hannun
鞘脂引起多种真核细胞反应，大多数涉及细胞生长、分化和凋亡的调节。1-磷酸鞘氨醇是一种鞘脂的分解代谢产物，在成纤维细胞中具有促有丝分裂作用，并抑制人类肿瘤细胞的趋化运动性和侵袭性。1-磷酸鞘氨醇降解需要通过磷酸鞘氨醇裂解酶在C2-3碳键处裂解。利用酵母遗传学方法克隆了第一个磷酸鞘氨醇裂解酶基因BST 1。BST 1过表达可使酵母对鞘氨醇产生抗性，BST 1缺失可使酵母对外源性β-鞘氨醇和植物鞘氨醇产生敏感性，并使1-磷酸鞘氨醇在酵母细胞内积累。这项研究证实，鞘氨醇碱代谢在所有真核生物中是相似的，并表明酵母遗传学可能是有用的，在鞘脂信号转导和代谢参与的其他基因的分离和鉴定。
Sphingolipids elicit a wide variety of eukaryotic cellular responses, most involving regulation of cell growth, differentiation, and apoptosis. Sphingosine 1-phosphate, a sphingolipid catabolite, is mitogenic in fibroblasts and inhibits the chemotactic mobility and invasiveness of human tumor cells. Sphingosine 1-phosphate degradation requires cleavage at the C2–3 carbon bond by sphingosine phosphate lyase. A yeast genetic approach was used to clone the first sphingosine phosphate lyase gene, BST1. BST1 overexpression conferred resistance to sphingosine in yeast.BST1 deletion produced sensitivity to exogenousd-erythro-sphingosine and phytosphingosine and intracellular accumulation of sphingosine 1-phosphate upon exposure to exogenous sphingosine. This study confirms that sphingoid base metabolism is similar in all eukaryotes and suggests that yeast genetics may be useful in the isolation and identification of other genes involved in sphingolipid signaling and metabolism.