SREBP-2, A 2ND BASIC-HELIX-LOOP-HELIX-LEUCINE ZIPPER PROTEIN THAT STIMULATES TRANSCRIPTION BY BINDING TO A STEROL REGULATORY ELEMENT
SREBP-2, A 2ND BASIC-HELIX-LOOP-HELIX-LEUCINE ZIPPER PROTEIN THAT STIMULATES TRANSCRIPTION BY BINDING TO A STEROL REGULATORY ELEMENT
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DOI：
10.1073/pnas.90.24.11603
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发表时间：
1993-12-15
影响因子：
11.1
通讯作者：
WANG, XD
中科院分区：
文献类型：
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作者：
HUA, XX;YOKOYAMA, C;WANG, XD
我们报道了识别甾醇调控元件1 （SRE-1）的碱性-螺旋-环-螺旋-亮氨酸拉链（bHLH-Zip）转录因子家族的第二个成员SREBP-2的cDNA克隆。SRE-1是低密度脂蛋白受体和3-羟基-3-甲基戊二酰辅酶a合成酶基因启动子中的条件增强子，在缺乏甾醇时增加转录，当甾醇积累时失活。人类SREBP-2含有1141个氨基酸，与人类SREBP-la（该家族的第一个成员）相同47%。相似之处包括一个酸性的NH2末端，一个高度保守的bHLH-Zip基模（71%相同），以及bHLH-Zip区域cooh末端异常长的740个氨基酸。SREBP-2具有srebp -1a所缺乏的一个特征，即富含谷氨酰胺的区域（121个残基中有27%的谷氨酰胺）。在体外，SREBP-2结合SRE-1具有与SREBP-1a相同的特异性。在体内，它模仿SREBP-1a激活含有SRE-1的报告基因的转录。与SREBP-1a一样，SREBP-2的激活发生在缺乏和存在固醇的情况下，从而取消了调控。将少量pSREBP-1a和pSREBP-2共转染到人胚胎肾293细胞中，以加性方式刺激了含有SRE-1的启动子的转录。在高水平上，转录达到最大值，并且影响不再是加性的。两种srebp存在的原因以及它们受甾醇调节的机制仍有待确定。
We report the cDNA cloning of SREBP-2, the second member of a family of basic-helix-loop-helix-leucine zipper (bHLH-Zip) transcription factors that recognize sterol regulatory element 1 (SRE-1). SRE-1, a conditional enhancer in the promoters for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A synthase genes, increases transcription in the absence of sterols and is inactivated when sterols accumulate. Human SREBP-2 contains 1141 amino acids and is 47% identical to human SREBP-la, the first recognized member of this family. The resemblance includes an acidic NH2 terminus, a highly conserved bHLH-Zip motif (71% identical), and an unusually long extension of 740 amino acids on the COOH-terminal side of the bHLH-Zip region. SREBP-2 possesses one feature lacking in SREBP-1a-namely, a glutamine-rich region (27% glutamine over 121 residues). In vitro SREBP-2 bound SRE-1 with the same specificity as SREBP-1a. In vivo it mimicked SREBP-1a in activating transcription of reporter genes containing SRE-1. As with SREBP-1a, activation by SREBP-2 occurred in the absence and presence of sterols, abolishing regulation. Cotransfection of low amounts of pSREBP-1a and pSREBP-2 into human embryonic kidney 293 cells stimulated transcription of promoters containing SRE-1 in an additive fashion. At high levels transcription reached a maximum, and the effects were no longer additive. The reason for the existence of two SREBPs and the mechanism by which they are regulated by sterols remain to be determined.