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  • Title: Cyclin D1 activation through ATF-2 in Reg-induced pancreatic beta-cell regeneration.
    Author: Takasawa S, Ikeda T, Akiyama T, Nata K, Nakagawa K, Shervani NJ, Noguchi N, Murakami-Kawaguchi S, Yamauchi A, Takahashi I, Tomioka-Kumagai T, Okamoto H.
    Journal: FEBS Lett; 2006 Jan 23; 580(2):585-91. PubMed ID: 16405968.
    Abstract:
    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.
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