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Title: Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-? signaling
Authors: Nagano Y.
Mavrakis K.J.
Kian L.L. 
Fujii T.
Koinuma D.
Sase H.
Yuki K.
Isogaya K.
Saitoh M.
Imamura T.
Episkopou V.
Miyazono K.
Miyazawa K.
Issue Date: 2007
Citation: Nagano Y., Mavrakis K.J., Kian L.L., Fujii T., Koinuma D., Sase H., Yuki K., Isogaya K., Saitoh M., Imamura T., Episkopou V., Miyazono K., Miyazawa K. (2007). Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-? signaling. Journal of Biological Chemistry 282 (28) : 20492-20501. ScholarBank@NUS Repository.
Abstract: Transforming growth factor-? (TGF-?) signaling is controlled by a variety of regulators that target either signaling receptors or activated Smad complexes. Among the negative regulators, Smad7 antagonizes TGF-? 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-? 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-? 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-? family signaling in target cells. � 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
ISSN: 219258
DOI: 10.1074/jbc.M701294200
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