在Reg诱导的胰腺β细胞再生过程中，通过激活转录因子2（ATF-2）实现细胞周期蛋白D1的激活。
Cyclin D1 activation through ATF-2 in Reg-induced pancreatic beta-cell regeneration.
作者信息
Takasawa Shin, Ikeda Takayuki, Akiyama Takako, Nata Koji, Nakagawa Kei, Shervani Nausheen J, Noguchi Naoya, Murakami-Kawaguchi Shoko, Yamauchi Akiyo, Takahashi Iwao, Tomioka-Kumagai Tomoko, Okamoto Hiroshi
机构信息
Department of Biochemistry, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai 980-8575, Japan.
出版信息
FEBS Lett. 2006 Jan 23;580(2):585-91. doi: 10.1016/j.febslet.2005.12.070. Epub 2005 Dec 29.
Regenerating gene product (Reg) is induced in pancreatic beta-cells and acts as an autocrine/paracrine growth factor for regeneration via a cell surface Reg receptor. However, the manner by which Reg induces beta-cell regeneration was unknown. In the present study, we found that Reg increased phospho-ATF-2, which binds to -57 to -52 of the cyclin D1 gene to activate the promoter. The Reg/ATF-2-induced cyclin D1 promoter activation was attenuated by PI(3)K inhibitors such as LY294002 and wortmannin. In Reg knockout mouse islets, the levels of phospho-ATF-2, cyclin D1, and phospho-Rb were greatly decreased. These results indicate that the Reg-Reg receptor system stimulates the PI(3)K/ATF-2/cyclin D1 signaling pathway to induce beta-cell regeneration.
再生基因产物（Reg）在胰腺β细胞中被诱导，并通过细胞表面Reg受体作为自分泌/旁分泌生长因子促进再生。然而，Reg诱导β细胞再生的方式尚不清楚。在本研究中，我们发现Reg增加了磷酸化ATF-2，其与细胞周期蛋白D1基因的-57至-52位点结合以激活启动子。Reg/ATF-2诱导的细胞周期蛋白D1启动子激活被PI(3)K抑制剂如LY294002和渥曼青霉素减弱。在Reg基因敲除小鼠胰岛中，磷酸化ATF-2、细胞周期蛋白D1和磷酸化Rb的水平大大降低。这些结果表明Reg-Reg受体系统刺激PI(3)K/ATF-2/细胞周期蛋白D1信号通路以诱导β细胞再生。
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