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Mol Cell Biol. 2004 Mar;24(6):2251-62.

Jab1/CSN5, a component of the COP9 signalosome, regulates transforming growth factor beta signaling by binding to Smad7 and promoting its degradation.

Author information

  • 1Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-5055, USA.

Abstract

Smad7 inhibits responses mediated by transforming growth factor beta (TGF-beta) and acts in a negative-feedback loop to regulate the intensity or duration of the TGF-beta signal. However, the aberrant expression and continued presence of Smad7 may cause TGF-beta 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-beta-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-beta signaling.

PMID:
14993265
[PubMed - indexed for MEDLINE]
PMCID:
PMC355855
Free PMC Article

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