| Ubiquitin-specific protease 4 mitigates Toll-like/interleukin-1 receptor signaling and regulates innate immune activation. | |
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MedLine Citation:
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PMID: 22262844 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Fangfang Zhou; Xiaofei Zhang; Hans van Dam; Peter Ten Dijke; Huizhe Huang; Long Zhang |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-19 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Leiden University Medical Center, Netherlands. |
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