期刊
PLOS PATHOGENS
卷 9, 期 6, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1003480
关键词
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资金
- National Natural Science Foundation of China [31030021, 81161120542]
- Ministry of Science and Technology of China [2012CB910200, 2011CB910900, 2010CB529703]
- China Postdoctoral Science Foundation
The signaling of Toll-like receptors (TLRs) induces host defense against microbial invasion. Protein posttranslational modifications dynamically shape the strength and duration of the signaling pathways. It is intriguing to explore whether de-SUMOylation could modulate the TLR signaling. Here we identified SUMO-specific protease 6 (SENP6) as an intrinsic attenuator of the TLR-triggered inflammation. Depletion of SENP6 significantly potentiated the NF-kappa B-mediated induction of the proinflammatory genes. Consistently, SENP6-knockdown mice were more susceptible to endotoxin-induced sepsis. Mechanistically, the small ubiquitin-like modifier 2/3 (SUMO-2/3) is conjugated onto the Lysine residue 277 of NF-kappa B essential modifier (NEMO/IKK gamma), and this impairs the deubiquitinase CYLD to bind NEMO, thus strengthening the inhibitor of kappa B kinase (IKK) activation. SENP6 reverses this process by catalyzing the de-SUMOylation of NEMO. Our study highlights the essential function of the SENP family in dampening TLR signaling and inflammation.
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