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Transcriptional induction of Smurf2 ubiquitin ligase by TGF‐β
Author(s) -
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
Publication year - 2005
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.2005.03.069
Subject(s) - smad , ubiquitin ligase , transforming growth factor , ubiquitin , smad2 protein , microbiology and biotechnology , chemistry , signal transduction , r smad , pi3k/akt/mtor pathway , tgf alpha , biology , cancer research , receptor , growth factor , biochemistry , gene
Smad ubiquitination regulatory factor 2 (Smurf2), a ubiquitin ligase for Smads, plays critical roles in the regulation of transforming growth factor‐β (TGF‐β)‐Smad signaling via ubiquitin‐dependent degradation of Smad2 and Smad7. We found that TGF‐β stimulates Smurf2 expression. TGF‐β activated the Smurf2 promoter in a TGF‐β responsive cell lines, whereas IL‐1α, PDGF and epidermal growth factor did not. TGF‐β‐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‐β‐mediated Smurf2 induction. These results suggest that TGF‐β stimulates Smurf2 expression by Smad‐independent pathway such as PI3K/Akt pathway via TGF‐β receptor.