Document Detail


Ubiquitin-specific protease 4 mitigates Toll-like/interleukin-1 receptor signaling and regulates innate immune activation.
MedLine Citation:
PMID:  22262844     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The Toll-like receptor (TLR)/interleukin 1 receptor (IL-1R) signaling pathway is essential for innate immune responses and immune homeostasis. Lysine 63 polyubiquitinated Tumor necrosis factor receptor-associated factor (TRAF)6 mediates its downstream signaling activation. In a gain of expression screen of 66 different deubiquitinating enzymes (DUBs), we identified ubiquitin-specific protease (USP)4 as a potent negative regulator of TLR/IL-1R signaling and TRAF6 interacting protein. USP4 deubiquitinates TRAF6 and thereby prevents the activation of NF-κB and AP-1 transcriptional factors and subsequent pro-inflammatory responses. LPS-treated usp4-depleted zebrafish larvaes expressed higher levels of pro-inflammatory cytokines and were more susceptible to endotoxic challenge. Taken together, our results demonstrate that USP4 plays an essential role in negative regulation of the TLR-IL-1R signaling-mediated innate immune response.
Authors:
Fangfang Zhou; Xiaofei Zhang; Hans van Dam; Peter Ten Dijke; Huizhe Huang; Long Zhang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-19
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Leiden University Medical Center, Netherlands.
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