Nitz Inke, Döring Frank, Schrezenmeir Jürgen, Burwinkel Barbara
Molecular Nutrition, Christian-Albrechts University of Kiel, Hermann-Weigmann-Strasse 1, D-24103 Kiel, Germany.
Int J Biochem Cell Biol. 2005 Nov;37(11):2395-405. doi: 10.1016/j.biocel.2005.06.008.
The ubiquitously expressed acyl-CoA binding protein (ACBP) is involved in lipid metabolism and is regulated by hormones and feeding status via transcription factors such as sterol regulatory element-binding protein 1 and peroxisome proliferator-activated receptor-gamma (PPARgamma). In humans, two transcripts encoding proteins of 86 and 104 amino acids are known, whereas in mouse only one protein of 86 amino acids is described. We identified new transcripts in human and mouse tissues, that had been generated by alternative first exon usage. Quantitative RT-PCR analyses showed a high expression of the new human transcript, ACBP-1c, in adipose tissue. By promoter reporter gene assays, specific regulation of this transcript by PPARgamma2 was revealed, implicating the usage of an alternative promoter that contains a PPARgamma responsive element. Subcellular localizations of the known human proteins and the new variant showed an occurrence in cytoplasma and nucleus. Reported studies concerning ACBP gene regulation should be re-evaluated with respect to a new ACBP gene model. Given the fact that the new variant is highly expressed in adipose tissue and a PPARgamma target, it might be relevant for diseases like diabetes and obesity.
普遍表达的酰基辅酶A结合蛋白（ACBP）参与脂质代谢，并通过转录因子如固醇调节元件结合蛋白1和过氧化物酶体增殖物激活受体γ（PPARγ）受激素和进食状态的调节。在人类中，已知有两种转录本编码86和104个氨基酸的蛋白质，而在小鼠中仅描述了一种86个氨基酸的蛋白质。我们在人类和小鼠组织中鉴定出了通过选择性使用第一个外显子产生的新转录本。定量逆转录-聚合酶链反应（RT-PCR）分析显示，新的人类转录本ACBP-1c在脂肪组织中高表达。通过启动子报告基因检测，揭示了PPARγ2对该转录本的特异性调节，这意味着使用了一个含有PPARγ反应元件的替代启动子。已知人类蛋白质和新变体的亚细胞定位显示它们存在于细胞质和细胞核中。关于ACBP基因调节的已报道研究应根据新的ACBP基因模型重新评估。鉴于新变体在脂肪组织中高表达且是PPARγ的靶标，它可能与糖尿病和肥胖等疾病有关。
