Sci Rep. 2012;2:251. doi: 10.1038/srep00251. Epub 2012 Feb 7.
High-mobility group AT-hook 1 (HMGA1) protein is an important nuclear factor that activates gene transcription by binding to AT-rich sequences in the promoter region of DNA. We previously demonstrated that HMGA1 is a key regulator of the insulin receptor (INSR) gene and individuals with defects in HMGA1 have decreased INSR expression and increased susceptibility to type 2 diabetes mellitus. In addition, there is evidence that intracellular regulatory molecules that are employed by the INSR signaling system are involved in post-translational modifications of HMGA1, including protein phosphorylation. It is known that phosphorylation of HMGA1 reduces DNA-binding affinity and transcriptional activation. In the present study, we investigated whether activation of the INSR by insulin affected HMGA1 protein phosphorylation and its regulation of gene transcription. Collectively, our findings indicate that HMGA1 is a novel downstream target of the INSR signaling pathway, thus representing a new critical nuclear mediator of insulin action and function.
高迁移率族蛋白 A1（HMGA1）蛋白是一种重要的核因子，通过与 DNA 启动子区域富含 AT 的序列结合来激活基因转录。我们之前的研究表明，HMGA1 是胰岛素受体（INSR）基因的关键调节因子，HMGA1 缺陷的个体 INSR 表达降低，患 2 型糖尿病的易感性增加。此外，有证据表明，INSR 信号系统中使用的细胞内调节分子参与 HMGA1 的翻译后修饰，包括蛋白质磷酸化。已知 HMGA1 的磷酸化会降低 DNA 结合亲和力和转录激活。在本研究中，我们研究了胰岛素对 INSR 的激活是否影响 HMGA1 蛋白磷酸化及其对基因转录的调节。总之，我们的研究结果表明，HMGA1 是 INSR 信号通路的一个新的下游靶标，因此代表了胰岛素作用和功能的一个新的关键核介导物。
