ACYL-COA-BINDING PROTEIN DIAZEPAM-BINDING INHIBITOR GENE AND PSEUDOGENES - A TYPICAL HOUSEKEEPING GENE FAMILY

ACYL-COA-BINDING PROTEIN DIAZEPAM-BINDING INHIBITOR GENE AND PSEUDOGENES - A TYPICAL HOUSEKEEPING GENE FAMILY
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DOI:
10.1016/0022-2836(92)90888-q
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发表时间:
1992-12-05
影响因子:
5.6
通讯作者:
KRISTIANSEN, K
KRISTIANSEN, K
中科院分区:
生物学2区
文献类型:
--
作者:
MANDRUP, S;HUMMEL, R;KRISTIANSEN, K

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酰基辅酶A结合蛋白(ACBP)是从牛肝脏中分离的一种10 kDa的蛋白质,具有结合和诱导中链酰基辅酶A酯合成的能力。令人惊讶的是,它原来是相同的蛋白质命名为安定结合抑制剂(DBI)声称是一种内源性调节剂的GABA受体在大脑膜。ACBP/DBI或ACBP/DBI的蛋白水解衍生的多肽也涉及线粒体中类固醇生成和葡萄糖刺激的胰岛素分泌的控制。因此,ACBP/DBI似乎是一种显著的多功能蛋白质。目前,我们已成功地克隆了大鼠ACBP/DBI基因家族,并对其进行了分子生物学鉴定。大鼠ACBP/DBI基因家族包括一个表达基因和四个加工假基因,其中一个被证明以两种等位基因形式存在。表达的基因由四个外显子和三个内含子组成。核磁共振氢谱测定的ACBP/DBI结构模块与ACBP/DBI基因的外显子内含子结构之间存在显著的对应关系。对ACBP/DBI基因在脑和肝中的转录进行详细分析,以绘制转录起始位点,并检查ACBP/DBI基因的转录物是否受到替代处理。在大脑和肝脏中,转录起始于两个主要和多个次要起始位点。没有获得选择性剪接的证据。ACBP/DBI基因的启动子区位于CpG岛上,缺乏典型的TATA盒。因此,ACDB/DBI基因表现出典型管家基因的所有特征。
Acyl-CoA-binding protein (ACBP) is a 10 kDa protein isolated from bovine liver by virtue of its ability to bind and induce the synthesis of medium-chain acyl-CoA esters. Surprisingly, it turned out to be identical to a protein named diazepam-binding Inhibitor (DBI) claimed to be an endogenous modulator of the GABAAreceptor in brain membranes. ACBP/DBI, or proteolytically derived polypeptides of ACBP/DBI, have also been implicated in the control of steroidogenesis in mitochondria and glucose-stimulated insulin secretion. Thus, it appears that ACBP/DBI is a remarkable, versatile protein. Now we have molecularly cloned and characterized the ACBP/DBI gene family in rat. The rat ACBP/DBI gene family comprises one expressed gene and four processed pseudogenes of which one was shown to exist in two allelic forms. The expressed gene is organized into four exons and three introns. There is a remarkable correspondence between the structural modules of ACBP/DBI as determined by1H nuclear magnetic resonance spectroscopy and the exonintron architecture of the ACBP/DBI gene. Detailed analyses of transcription of the ACBP/DBI gene in brain and liver were performed to map transcription initiation sites and to examine if transcripts from the ACBP/DBI gene were subject to alternative processing. In both brain and liver, transcription is initiated from two major and multiple minor initiation sites. No evidence for alternative splicing was obtained. The promoter region of the ACBP/DBI gene is located in a CpG island and lacks a canonical TATA box. Thus, the ACDB/DBI gene exhibits all the hallmarks of a typical housekeeping gene.