TY - JOUR
T1 - Cyclin D1 activation through ATF-2 in Reg-induced pancreatic β-cell regeneration
AU - Takasawa, Shin
AU - Ikeda, Takayuki
AU - Akiyama, Takako
AU - Nata, Koji
AU - Nakagawa, Kei
AU - Shervani, Nausheen J.
AU - Noguchi, Naoya
AU - Murakami-Kawaguchi, Shoko
AU - Yamauchi, Akiyo
AU - Takahashi, Iwao
AU - Tomioka-Kumagai, Tomoko
AU - Okamoto, Hiroshi
N1 - Funding Information:
We thank Brent Bell for valuable assistance in preparing the manuscript for publication, Drs. Yoichi Narushima, Ichiro Kato, Tohru Onogawa, and Michiaki Abe and Mr. Yuya Shichinohe for their kind help. This work was supported in part by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan and Public Trust Haraguchi Memorial Cancer Research Fund, Tokyo, Japan, and is partial fulfillment of the degree of Doctor of Medical Science at Tohoku University of T.T.-K. T.A. is a recipient of a fellowship from the Japan Society for the Promotion of Science.
PY - 2006/1/23
Y1 - 2006/1/23
N2 - 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.
AB - 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.
KW - Cyclin D1, ATF-2, PI(3)K
KW - Knockout mouse
KW - Pancreatic β-cell
KW - Reg
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U2 - 10.1016/j.febslet.2005.12.070
DO - 10.1016/j.febslet.2005.12.070
M3 - Article
C2 - 16405968
AN - SCOPUS:30644464050
SN - 0014-5793
VL - 580
SP - 585
EP - 591
JO - FEBS Letters
JF - FEBS Letters
IS - 2
ER -