Alternative splicing produces a constitutively active form of human SREBP-1
Alternative splicing produces a constitutively active form of human SREBP-1
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DOI：
10.1016/j.bbrc.2008.02.004
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发表时间：
2008-04-11
影响因子：
3.1
通讯作者：
Nakaya, Yutaka
中科院分区：
文献类型：
--
作者：
Harada, Nagakatsu;Yonemoto, Haruka;Nakaya, Yutaka
我们鉴定了一种新的选择性剪接事件，它结构性地产生截短的活性形式的人固醇调节元件结合蛋白1(SREBP-1)。这种剪接变异体的一个cDNA(命名为SREBP-1 Delta)包含一个位于外显子7和8之间的翻译终止密码子编码的外显子序列。它产生SREBP-1a Delta(470 A.A.)和SREBP-1c Delta(446A.A.)缺少将SREBP-1定位到内质网所必需的跨膜和C末端调控序列的蛋白质。荧光素酶报告基因分析表明，SREBP-1a Delta和SREBP-1c Delta的反式激活程度分别与SREBP-1a和SREBP-1c的N端活性片段相同。SREBP-1 Delta mRNA在人类细胞系以及脂肪和肝组织中表达。SREBP-1的表达水平从5%到16%不等。胰岛素或高糖处理均不影响HepG2细胞SREBP-1 Delta表达与总SREBP-1表达的比值。(C)2008 Elsevier Inc.保留所有权利。
We identified a novel alternative splicing event that constitutively produces a truncated active form of human sterol regulatory element-binding protein 1 (SREBP-1). A cDNA of this splicing variant (named SREBP-1 Delta) contains a translational stop codon-encoding exon sequence between exons 7 and 8. It produces SREBP-1a Delta (470 a.a.) and SREBP-1c Delta (446 a.a.) proteins that lack transmembrane and C-terminal regulatory sequences necessary for localization of SREBP-1 to the endoplasmic reticulum. A luciferase reporter assay showed that SREBP-1a Delta and SREBP-1c Delta transactivated lipogenic gene promoters to the same extent as that induced by N-terminal active fragments of SREBP-1a and SREBP-1c, respectively. SREBP-1 Delta mRNA is expressed in human cell lines as well as adipose and liver tissues. Expression levels ranged from 5% to 16% of total SREBP-1 expression. The ratio of SREBP-1 Delta expression to total SREBP-1 expression in HepG2 cells was not affected by either insulin or high glucose treatment. (c) 2008 Elsevier Inc. All rights reserved.