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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Independent regulation of sterol regulatory element-binding proteins 1 and 2 in hamster liver.
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Independent regulation of sterol regulatory element-binding proteins 1 and 2 in hamster liver.

机译：仓鼠肝脏中固醇调节元素结合蛋白1和2的独立调节。

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摘要

Two sterol regulatory element-binding proteins (SREBPs, designated SREBP-1 and SREBP-2), each approximately 1150 amino acids in length, are attached to membranes of the endoplasmic reticulum and nuclear envelope in human and hamster tissue culture cells. In the absence of sterols, soluble fragments of approximately 470 amino acids are released from both proteins by proteolytic cleavage. The soluble fragments enter the nucleus, where they bind to sterol regulatory elements in the promoters of genes encoding the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl CoA synthase, thereby activating transcription. Proteolytic processing of both SREBPs is blocked coordinately by sterol overloading and enhanced coordinately when sterols are depleted by treatment with an inhibitor of cholesterol synthesis. In contrast to these findings in cultured cells, the current data show that SREBP-1 and -2 are not coordinately regulated in hamster liver. In untreated animals the soluble fragment of SREBP-1, but not of SREBP-2, was detected by immunoblotting of a liver nuclear extract. Depletion of sterols by treatment with a bile acid-binding resin (colestipol) and a cholesterol synthesis inhibitor (mevinolin) led to a marked increase in the nuclear form of SREBP-2 and a reciprocal decline in the nuclear form of SREBP-1. These findings suggest that SREBP-1 is responsible for basal transcription of the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl CoA synthase genes in hamster liver and that SREBP-2 is responsible for the increased transcription that follows sterol depletion with a bile acid-binding resin and a cholesterol synthesis inhibitor.
机译：两个固醇调节元件结合蛋白（SREBP，分别命名为SREBP-1和SREBP-2）长约1150个氨基酸，它们附着在人和仓鼠组织培养细胞的内质网和核膜上。在没有固醇的情况下，通过蛋白水解切割从两种蛋白质中释放出约470个氨基酸的可溶性片段。可溶性片段进入细胞核，并与编码低密度脂蛋白受体和3-羟基-3-甲基戊二酰辅酶A合酶的基因启动子中的固醇调节元件结合，从而激活转录。两种SREBP的蛋白水解过程均通过固醇过载而被阻断，并且当通过用胆固醇合成抑制剂处理而耗尽固醇时，其协同地被增强。与在培养细胞中发现的结果相反，当前数据表明，SREBP-1和-2在仓鼠肝脏中不受协调调节。在未经处理的动物中，通过免疫印迹检测肝核提取物可检测到SREBP-1的可溶性片段，但未检测到SREBP-2的可溶性片段。通过用胆汁酸结合树脂（colestipol）和胆固醇合成抑制剂（mevinolin）处理来减少固醇会导致SREBP-2的核形式显着增加，而SREBP-1的核形式则相应地减少。这些发现表明，SREBP-1负责仓鼠肝脏中低密度脂蛋白受体和3-hydroxy-3-methylglutaryl CoA合酶基因的基础转录，而SREBP-2负责在胆固醇被胆汁耗尽后增加转录。酸结合树脂和胆固醇合成抑制剂。

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