Proteasomal regulation of HNF4 alpha protein by hypoxia in pancreatic beta-cells.

HNF4 α是一种β细胞转录因子，是胰腺β细胞分泌胰岛素的关键分子。虽然我们发现缺氧显著降低了HNF4 α蛋白，但其分子机制目前尚不清楚。在这项研究中，我们证明了缺氧诱导的AMPK激活抑制HNF4 α蛋白水平不是通过转录调节，而是通过泛素-蛋白酶体途径介导的体外降解。体内缺氧或AMPK激活剂是否会降低HNF4 α蛋白，还需要进一步的实验来验证。

HNF4 alpha, a beta-cell transcriptional factor, is a key molecule for insulin secretion from pancreatic beta-cells. Although we found that HNF4 alpha protein was significantly reduced by hypoxia, its molecular mechanism was unclear so far. In this study, we demonstrated that hypoxia-induced activation of AMPK suppresses HNF4 alpha protein levels not via transcriptional regulation, but via ubiquitin-proteasome pathway mediated degradation in vitro. Further experiments are needed to see whether HNF4 alpha protein might be reduced by hypoxia or AMPK activators in vivo.