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首页> 外文期刊>Cellular Physiology and Biochemistry >Transcriptional Regulation of HMG-CoA Synthase and HMG-CoA Reductase Genes by Human ACBP
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Transcriptional Regulation of HMG-CoA Synthase and HMG-CoA Reductase Genes by Human ACBP

机译：人类ACBP对HMG-CoA合酶和HMG-CoA还原酶基因的转录调控

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摘要

The acyl-CoA binding protein (ACBP) is an ubiquitary expressed multi-functional protein which regulates basic cellular functions such as fatty acid and steroid metabolism. Since ACBP is described to interact with the transcription factor hepatocyte nuclear factor 4 alpha (HNF-4 alpha), we investigated the role of human ACBP on transcriptional regulation of the putative HNF-4 alpha target gene HMG-CoA synthase 1 (HMGCS1). As shown by promoter-reporter assays ACBP represses the HNF-4 alpha-induced activity of a 617bp HMGCS1 promoter fragment by approximately 80% in HepG2 cells as well as in non-endodermal HeLa cells devoid of HNF-4 alpha. Interestingly, reporter assays without co-transfection of HNF-4 alpha revealed that ACBP reduces the activity of the HMGCS1 promoter by about 60 to 80% in both cell lines. Activities of 417bp and 317bp HMGCS1 promoter fragments were 2.5 to 4 fold decreased by ACBP. Concordantly, the levels of HMGCS1-mRNA and protein were diminished to 60% and 70% in ACBP-expressing HeLa cells, respectively. Additionally, ACBP reduces the promoter activity and the mRNA levels of the cholesterogenic HMG-CoA reductase (HMGCR). In conclusion, we provide evidence that ACBP is a transcriptional regulator of the HMGCS1 and HMGCR genes encoding rate-limiting enzymes of cholesterol synthesis pathway.
机译：酰基辅酶A结合蛋白（ACBP）是一种普遍表达的多功能蛋白，可调节基本的细胞功能，例如脂肪酸和类固醇的代谢。由于ACBP被描述为与转录因子肝细胞核因子4α（HNF-4 alpha）相互作用，因此我们研究了人ACBP在假定的HNF-4α目标基因HMG-CoA合酶1（HMGCS1）的转录调控中的作用。如启动子-报告分析所示，ACBP在HepG2细胞和不含HNF-4α的非内胚层HeLa细胞中，将617bp HMGCS1启动子片段的HNF-4α诱导的活性抑制了约80％。有趣的是，没有共转染HNF-4α的报告基因检测表明，ACBP在两种细胞系中均将HMGCS1启动子的活性降低了约60％至80％。 ACBP将417bp和317bp HMGCS1启动子片段的活性降低了2.5到4倍。一致地，在表达ACBP的HeLa细胞中，HMGCS1-mRNA和蛋白质的水平分别降低至60％和70％。另外，ACBP会降低启动子活性和产胆固醇的HMG-CoA还原酶（HMGCR）的mRNA水平。总之，我们提供的证据表明ACBP是HMGCS1和HMGCR基因的转录调节因子，编码胆固醇合成途径的限速酶。

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