2007年7月13日
Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-beta signaling.
The Journal of biological chemistry
- 巻
- 282
- 号
- 28
- 開始ページ
- 20492
- 終了ページ
- 501
- 記述言語
- 英語
- 掲載種別
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.
- リンク情報
- ID情報
-
- ISSN : 0021-9258
- PubMed ID : 17510063