| Autor: |
Koinuma D; Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Toshima-ku, Tokyo, Japan., Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, Ebina M, Nukiwa T, Miyazawa K, Imamura T, Miyazono K |
| Jazyk: |
angličtina |
| Zdroj: |
The EMBO journal [EMBO J] 2003 Dec 15; Vol. 22 (24), pp. 6458-70. |
| DOI: |
10.1093/emboj/cdg632 |
| Abstrakt: |
Arkadia was originally identified as a protein that enhances signalling activity of Nodal and induces mammalian nodes during early embryogenesis; however, the mechanisms by which Arkadia affects transforming growth factor-beta (TGF-beta) superfamily signalling have not been determined. Here we show that Arkadia is widely expressed in mammalian tissues, and that it enhances both TGF-beta and bone morphogenetic protein (BMP) signalling. Arkadia physically interacts with inhibitory Smad, Smad7, and induces its poly-ubiquitination and degradation. In contrast to Smurf1, which interacts with TGF-beta receptor complexes through Smad7 and degrades them, Arkadia fails to associate with TGF-beta receptors. In contrast to Smad7, expression of Arkadia is down-regulated by TGF-beta. Silencing of the Arkadia gene resulted in repression of transcriptional activities induced by TGF-beta and BMP, and accumulation of the Smad7 protein. Arkadia may thus play an important role as an amplifier of TGF-beta superfamily signalling under both physiological and pathological conditions. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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