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SOCS3 Drives Proteasomal Degradation of TBK1 and Negatively Regulates Antiviral Innate Immunity.

Mol. Cell. Biol.. 2015; 
LiuDong,ShengChunjie,GaoShijuan,YaoChen,LiJiandong,JiangWei,ChenHuiming,WuJiaoxiang,PanChangchuan,ChenShuai,HuangWe
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Catalog Antibody he mouse anti-Flag (F3165) antibody was obtained from Sigma (USA). Rabbit Myc (A00172) and goat HA (A00168) antibodies were bought from Genscript (Nanjing, China).  Get A Quote

摘要

TANK-binding kinase 1 (TBK1)-mediated induction of type I interferon (IFN) plays a critical role in host antiviral responses and immune homeostasis. The negative regulation of TBK1 activity is largely unknown. We report that suppressor of cytokine signaling 3 (SOCS3) inhibits the IFN-β signaling pathway by promoting proteasomal degradation of TBK1. Overexpression and knockdown experiments indicated that SOCS3 is a negative regulator of IFN regulatory factor 3 (IRF3) phosphorylation and IFN-β transcription. Moreover, SOCS3 directly associates with TBK1, and they colocalize in the cytoplasm. SOCS3 catalyzes K48-linked polyubiquitination of TBK1 at Lys341 and Lys344 and promotes subsequent TBK1 degradation. ... More

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