Glauser Dominique A, Schlegel Werner
Medical Faculty, University of Geneva, Switzerland.
J Recept Signal Transduct Res. 2009 Dec;29(6):293-8. doi: 10.3109/10799890903241824.
Lack of nutrients and growth factors activates FoxO transcription factors in pancreatic beta-cells, whereas PI3K/Akt-dependent inactivation of FoxO favors proliferation. To address the link between FoxO and cell cycle control, we deprived Min6 cells of serum and glucose which activated FoxO and inhibited proliferation. Concomitantly, expression of the transcriptional repressor Bcl-6 was stimulated, whereas cyclin D2 was lowered. Gain of function approaches indicated that FoxO activation was sufficient to activate bcl-6 transcription, while Bcl-6 repressed cyclin D2 transcription and proliferation. Thus, in pancreatic beta-cells, the FoxO/Bcl6/cyclin D2 pathway connects nutrient and growth factor status to cell cycle control, and may therefore be considered for its therapeutic potential in diabetes.
营养物质和生长因子的缺乏会激活胰腺β细胞中的FoxO转录因子，而FoxO的PI3K/Akt依赖性失活则有利于细胞增殖。为了研究FoxO与细胞周期调控之间的联系，我们去除了Min6细胞中的血清和葡萄糖，这激活了FoxO并抑制了细胞增殖。与此同时，转录抑制因子Bcl-6的表达受到刺激，而细胞周期蛋白D2的表达则降低。功能获得实验表明，FoxO的激活足以激活bcl-6转录，而Bcl-6则抑制细胞周期蛋白D2的转录和细胞增殖。因此，在胰腺β细胞中，FoxO/Bcl6/细胞周期蛋白D2通路将营养物质和生长因子状态与细胞周期调控联系起来，因此可能因其在糖尿病治疗中的潜力而受到关注。
