Cyclin D1 activation through ATF-2 in Reg-induced pancreatic β-cell regeneration

Shin Takasawa, Takayuki Ikeda, Takako Akiyama, Koji Nata, Kei Nakagawa, Nausheen J. Shervani, Naoya Noguchi, Shoko Murakami-Kawaguchi, Akiyo Yamauchi, Iwao Takahashi, Tomoko Tomioka-Kumagai, Hiroshi Okamoto

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)585-591
Number of pages7
JournalFEBS Letters
Issue number2
Publication statusPublished - 2006 Jan 23


  • Cyclin D1, ATF-2, PI(3)K
  • Knockout mouse
  • Pancreatic β-cell
  • Reg

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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