| Literature DB >> 17510063 |
Yoshiko Nagano1, Konstantinos J Mavrakis, Kian Leong Lee, Tomoko Fujii, Daizo Koinuma, Hitoshi Sase, Keiko Yuki, Kazunobu Isogaya, Masao Saitoh, Takeshi Imamura, Vasso Episkopou, Kohei Miyazono, Keiji Miyazawa.
Abstract
Transforming growth factor-beta (TGF-beta) signaling is controlled by a variety of regulators that target either signaling receptors or activated Smad complexes. Among the negative regulators, Smad7 antagonizes TGF-beta signaling mainly through targeting the signaling receptors, whereas SnoN and c-Ski repress signaling at the transcriptional level through inactivation of Smad complexes. We previously found that Arkadia is a positive regulator of TGF-beta signaling that induces ubiquitin-dependent degradation of Smad7 through its C-terminal RING domain. We report here that Arkadia induces degradation of SnoN and c-Ski in addition to Smad7. Arkadia interacts with SnoN and c-Ski in their free forms as well as in the forms bound to Smad proteins, and constitutively down-regulates levels of their expression. Arkadia thus appears to effectively enhance TGF-beta signaling through simultaneous down-regulation of two distinct types of negative regulators, Smad7 and SnoN/c-Ski, and may play an important role in determining the intensity of TGF-beta family signaling in target cells.Entities:
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Year: 2007 PMID： 17510063 DOI： 10.1074/jbc.M701294200
Source DB: PubMed Journal: J Biol Chem ISSN： 0021-9258 Impact factor: 5.157