Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein
Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein
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DOI：
10.1016/s0092-8674(00)81362-8
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发表时间：
1996-11-01
期刊：
影响因子：
64.5
通讯作者：
Brown, MS
中科院分区：
文献类型：
--
作者：
Hua, XX;Nohturfft, A;Brown, MS
通过表达克隆，我们已经分离出一种cDNA编码的SREBP裂解激活蛋白（SCAP），它通过刺激转录因子SREBP-1和-2的裂解来调节胆固醇代谢，从而将它们从膜上释放出来。从中国仓鼠卵巢细胞中分离出cDNA，该细胞具有显性突变，使其对固醇介导的胆固醇合成和摄取抑制具有抗性。甾醇抗性可追溯到SCAP密码子443处的G->A转换，将天冬氨酸变为天冬酰胺。D443 N突变增强了SCAP的裂解刺激能力，并使其对固醇的抑制具有抗性。SCAP具有多个跨膜区域，其中五个类似于HMG CoA还原酶的甾醇敏感结构域，HMG CoA还原酶是一种内质网酶，其降解被甾醇加速。SCAP似乎是动物细胞中胆固醇代谢的中心调节剂。
Through expression cloning we have isolated a cDNA-encoding SREBP cleavage-activating protein (SCAP), which regulates cholesterol metabolism by stimulating cleavage of transcription factors SREBP-1 and -2, thereby releasing them from membranes. The cDNA was isolated from Chinese hamster ovary cells with a dominant mutation that renders them resistant to sterol-mediated suppression of cholesterol synthesis and uptake. Sterol resistance was traced to a G-->A transition at codon 443 of SCAP, changing aspartic acid to asparagine. The D443N mutation enhances the cleavage-stimulating ability of SCAP and renders it resistant to inhibition by sterols. SCAP has multiple membrane-spanning regions, five of which resemble the sterol-sensing domain of HMG CoA reductase, an endoplasmic reticulum enzyme whose degradation is accelerated by sterols. SCAP appears to be a central regulator of cholesterol metabolism in animal cells.