SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast
SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast
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DOI：
10.1016/j.cell.2005.01.012
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发表时间：
2005-03-25
期刊：
影响因子：
64.5
通讯作者：
Espenshade, PJ
中科院分区：
文献类型：
--
作者：
Hughes, AL;Todd, BL;Espenshade, PJ
哺乳动物中胆固醇和脂肪酸的合成受膜结合转录因子家族SREBP控制。我们的研究在粟酒裂殖酵母中鉴定了SREBP、其结合伴侣SCAP和ER滞留蛋白Insig的同源物，命名为sre 1（+）、scp 1（+）和ins 1（+）。与SREBP一样，Sre 1以Scp 1依赖性方式响应甾醇耗竭而被裂解和激活。微阵列分析表明，Sre 1激活甾醇生物合成酶在哺乳动物中，令人惊讶的是，Sre 1还刺激转录所需的基因适应缺氧。此外，Sre 1在低氧条件下迅速激活这些靶基因，并且本身也是厌氧生长所必需的。基于这些研究结果，我们提出并测试了一个模型，其中Sre 1和Scp 1监测氧依赖性甾醇合成作为一种间接措施的氧气供应和介导的缺氧反应在裂变酵母。
Cholesterol and fatty acid synthesis in mammals are controlled by SREBPs, a family of membrane bound transcription factors. Our studies identified homologs of SREBP, its binding partner SCAP, and the ER retention protein Insig in Schizosaccharomyces pombe, named sre1(+), scp1(+), and ins1(+). Like SREBP, Sre1 is cleaved and activated in response to sterol depletion in a Scp1-dependent manner. Microarray analysis revealed that Sre1 activates sterol biosynthetic enzymes as in mammals, and, surprisingly, Sre1 also stimulates transcription of genes required for adaptation to hypoxia. Furthermore, Sre1 rapidly activates these target genes in response to low oxygen and is itself required for anaerobic growth. Based on these findings, we propose and test a model in which Sre1 and Scp1 monitor oxygen-dependent sterol synthesis as an indirect measure of oxygen supply and mediate a hypoxic response in fission yeast.