Kuo Meishiue, Zilberfarb Vladimir, Gangneux Nicolas, Christeff Névéna, Issad Tarik
Institut Cochin, Université Paris Descartes, 22 Rue Méchain, CNRS (UMR 8104), Paris, France.
FEBS Lett. 2008 Mar 5;582(5):829-34. doi: 10.1016/j.febslet.2008.02.010. Epub 2008 Feb 14.
Mono-O-glycosylations post-translationally regulate the activity of nucleocytoplasmic proteins. We showed that glucosamine and an inhibitor of deglycosylation (PUGNAc) induced O-glycosylation of FoxO1, resulting in increased expression of a glucose-6-phosphatase reporter gene. This effect was independent of FoxO1 re-localisation, since it was also observed with constitutively nuclear FoxO1-AAA mutant. Moreover, in HepG2 cells, glucosamine and PUGNAc have a synergistic effect on the glucose-6-phosphatase reporter gene, and this effect was inhibited by FoxO1 siRNAs. Since glucose-6-phosphatase plays a key role in hepatic glucose production, our observation may be of importance with regard to glucotoxicity associated with chronic hyperglycaemia in diabetes.
单O-糖基化在翻译后调节核质蛋白的活性。我们发现氨基葡萄糖和去糖基化抑制剂（PUGNAc）可诱导FoxO1的O-糖基化，导致葡萄糖-6-磷酸酶报告基因的表达增加。这种效应与FoxO1的重新定位无关，因为在组成型核FoxO1-AAA突变体中也观察到了这种效应。此外，在HepG2细胞中，氨基葡萄糖和PUGNAc对葡萄糖-6-磷酸酶报告基因具有协同作用，并且这种效应被FoxO1 siRNA抑制。由于葡萄糖-6-磷酸酶在肝脏葡萄糖生成中起关键作用，我们的观察结果可能与糖尿病慢性高血糖相关的糖毒性有关。
