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

 Kyoung Seob Song  ;  Kyubo Kim  ;  Kwang Chul Chung  ;  Jae Hong Seol  ;  Joo-Heon Yoon 
 Biochemical and Biophysical Research Communications, Vol.377(3) : 946-951, 2008 
Journal Title
 Biochemical and Biophysical Research Communications 
Issue Date
Cell Line ; Gene Expression ; Humans ; Interleukin-1beta/genetics ; Interleukin-1beta/metabolism* ; Mucins/genetics* ; Nuclear Matrix-Associated Proteins/genetics ; Nuclear Matrix-Associated Proteins/metabolism* ; Octamer Transcription Factors/genetics ; Octamer Transcription Factors/metabolism* ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism* ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins/antagonists & inhibitors ; Suppressor of Cytokine Signaling Proteins/genetics ; Suppressor of Cytokine Signaling Proteins/metabolism* ; Transcriptional Activation* ; Ubiquitination
IL-1β ; Inflammation ; MUC8 ; SOCS3 ; NonO
The intracellular negatively regulatory mechanism which affects IL-1beta-induced MUC8 gene expression remains unclear. We found that SOCS3 overexpression suppressed IL-1beta-induced MUC8 gene expression in NCI-H292 cells, whereas silencing of SOCS3 restored IL-1beta-induced MUC8 gene expression. Sequentially activated ERK1/2, RSK1, and CREB by IL-1beta 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-1beta, whereas IL-1beta 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-1beta compared to NonO overexpression alone, suggesting that SOCS3 acts as a suppressor by regulating the action of NonO.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Airway Hucus Institute (기도점액연구소) > 1. Journal Papers
Yonsei Authors
Kim, Kyu Bo(김규보)
Song, Kyoung Seob(송경섭)
Yoon, Joo Heon(윤주헌)
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