Interaction of SOCS3 with NonO attenuates IL-1β-dependent MUC8 gene expression

Kyoung Seob Song, Kyubo Kim, Kwang Chul Chung, Jae Hong Seol, Joo Heon Yoon

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)946-951
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume377
Issue number3
DOIs
Publication statusPublished - 2008 Dec 19

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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