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Cyclin D1 activation through ATF‐2 in Reg‐induced pancreatic β‐cell regeneration
Author(s) -
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
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.12.070
Subject(s) - cyclin d1 , wortmannin , microbiology and biotechnology , paracrine signalling , autocrine signalling , cyclin , chemistry , cancer research , cyclin a2 , cyclin d , cyclin d2 , cyclin a , biology , signal transduction , cell cycle , receptor , phosphatidylinositol , cell , biochemistry
Regenerating gene product (Reg) is induced in pancreatic β‐cells and acts as an autocrine/paracrine growth factor for regeneration via a cell surface Reg receptor. However, the manner by which Reg induces β‐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 β‐cell regeneration.