| Autor: |
Byung-Chul Kim, Ho-Jae Lee, Satoshi, Seok Hee Park, Satoshi, Sae Ra Lee, Satoshi, Karpova, Tatiana S., McNally, James G., Felici, Angelina, Dug Keun Lee, Angelina, Seong-Jin Kim, Angelina |
| Předmět: |
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| Zdroj: |
Molecular & Cellular Biology; Mar2004, Vol. 24 Issue 6, p2251-2262, 12p, 3 Color Photographs, 14 Diagrams, 11 Graphs |
| Abstrakt: |
Smad7 inhibits responses mediated by transforming growth factor β (TGF-β) and acts in a negative feedback loop to regulate the intensity or duration of the TGF-β signal. However, the aberrant expression and continued presence of Smad7 may cause TGF-β resistance. Here we report that Jab1/CSN5, which is a component of the COP9 signalosome complex, associates constitutively with Smad7 and that overexpression of Jab1/CSN5 causes the translocation of Smad7 from the nucleus to the cytoplasm, promoting its degradation. Overexpression of Jab1/CSN5 increases Smad2 phosphorylation and enhances TGF-β-induced transcriptional activity. The inhibition of endogenous Jab1/CSN5 expression by small interfering RNA (siRNA) induces Smad7 expression. This study thus defines Jab1/CSN5 as an adapter that targets Smad7 for degradation, thus releasing Smad7-mediated suppression of TGF-β signaling. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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