Transcriptional induction of Smurf2 ubiquitin ligase by TGF-beta |
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| Authors: | Ohashi Naro Yamamoto Tatsuo Uchida Chiharu Togawa Akashi Fukasawa Hirotaka Fujigaki Yoshihide Suzuki Sayuri Kitagawa Kyoko Hattori Takayuki Oda Toshiaki Hayashi Hidetoshi Hishida Akira Kitagawa Masatoshi |
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| Affiliation: | First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan. ohashi-n@hama.med.ac.jp |
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| Abstract: | Smad ubiquitination regulatory factor 2 (Smurf2), a ubiquitin ligase for Smads, plays critical roles in the regulation of transforming growth factor-beta (TGF-beta)-Smad signaling via ubiquitin-dependent degradation of Smad2 and Smad7. We found that TGF-beta stimulates Smurf2 expression. TGF-beta activated the Smurf2 promoter in a TGF-beta responsive cell lines, whereas IL-1alpha, PDGF and epidermal growth factor did not. TGF-beta-mediated Smurf2 promoter activation was inhibited by Smad7 or an activin receptor-like kinase 5 inhibitor but not by dominant negative Smad or disruption of Smad-binding elements in the promoter. Moreover, inhibition of the phosphatidil inositol 3 kinase (PI3K)/Akt pathway suppressed TGF-beta-mediated Smurf2 induction. These results suggest that TGF-beta stimulates Smurf2 expression by Smad-independent pathway such as PI3K/Akt pathway via TGF-beta receptor. |
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| Keywords: | R-Smad, receptor-regulated Smad Smurf, Smad ubiquitination regulatory factor TGF-β, transforming growth factor-β ALK, activin receptor-like kinase PI3 kinase, phosphatidil inositol 3 kinase |
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