Iacobazzi Vito, Infantino Vittoria, Bisaccia Faustino, Castegna Alessandra, Palmieri Ferdinando
Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, Bari, Italy.
Biochem Biophys Res Commun. 2009 Jul 24;385(2):220-4. doi: 10.1016/j.bbrc.2009.05.030. Epub 2009 May 13.
In this study, we have investigated the transcriptional role of the FOXA site present in the promoter of the mitochondrial citrate carrier (CIC) gene. We have shown that wild-type (but not mutated) CIC FOXA site cloned in front of the luciferase promoter confers transcriptional activation of the gene reporter, particularly in cells overexpressing FOXA1. We have also demonstrated that overexpression and silencing of FOXA increases and reduces CIC transcript and protein levels, respectively. In addition, FOXA1 silencing in INS-1 cells decreases not only CIC mRNA and protein but also the amount of citrate in the cytosol and glucose-stimulated insulin secretion. These results show that FOXA plays a role in the transcriptional regulation of CIC and in insulin secretion.
在本研究中，我们研究了线粒体柠檬酸载体（CIC）基因启动子中存在的FOXA位点的转录作用。我们已经表明，克隆在荧光素酶启动子前的野生型（而非突变型）CIC FOXA位点可赋予基因报告基因转录激活，特别是在过表达FOXA1的细胞中。我们还证明，FOXA的过表达和沉默分别增加和降低了CIC转录本和蛋白质水平。此外，INS-1细胞中FOXA1的沉默不仅降低了CIC mRNA和蛋白质水平，还降低了细胞质中柠檬酸的含量以及葡萄糖刺激的胰岛素分泌。这些结果表明，FOXA在CIC的转录调控和胰岛素分泌中发挥作用。
