The intracellular negatively regulatory mechanism which affects IL-1β-induced MUC8 gene expression remains unclear. We found that SOCS3 overexpression suppressed IL-1β-induced MUC8 gene expression in NCI-H292 cells, whereas silencing of SOCS3 restored IL-1β-induced MUC8 gene expression. Sequentially activated ERK1/2, RSK1, and CREB by IL-1β were not affected by SOCS3, indicating that SOCS3 has an independent mechanism of action. Using immunoprecipitaion and nano LC mass analysis, we found that SOCS3 bound NonO (non-POU-domain containing, octamer-binding domain protein) in the absence of IL-1β, whereas IL-1β treatment dissociated the direct binding of SOCS3 and NonO. A dominant-negative SOCS3 mutant (Y204F/Y221F) did not bind to NonO. Interestingly, SOCS3 overexpression dramatically suppressed MUC8 gene expression in cells transfected with wild-type or siRNA of NonO. Moreover, silencing of SOCS3 dramatically increased NonO-mediated MUC8 gene expression caused by IL-1β compared to NonO overexpression alone, suggesting that SOCS3 acts as a suppressor by regulating the action of NonO.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2008 Dec 19|
Bibliographical noteFunding Information:
This study was supported by a Korean Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R11-2007-040-02001-0 for JHY), by Korea Research Foundation Grant KRF-2005-050-C00005 (for KSS), and by a faculty research grant of Yonsei University College of Medicine for 2007 (6-2007-0178 for KSS). The authors have no conflicting financial interests.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology