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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2011-9-28
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pubmed:abstractText |
The carboxyl terminus of constitutive heat shock cognate 70 (HSC70)-interacting protein (CHIP, also known as Stub1) is a U box-containing E3 ubiquitin ligase that is important for protein quality control. The role of CHIP in innate immunity is not known. Here, we report that CHIP knockdown inhibits Toll-like receptor (TLR) 4- and TLR9-driven signaling, but not TLR3-driven signaling; proinflammatory cytokine and type 1 interferon (IFN) production; and maturation of antigen-presenting cells, including macrophages and dendritic cells. We demonstrate that CHIP can recruit the tyrosine kinase Src and atypical protein kinase C ? (PKC?) to the TLR complex, thereby leading to activation of IL-1 receptor-associated kinase 1, TANK-binding kinase 1, and IFN regulatory factors 3 and 7. CHIP acts as an E3 ligase for Src and PKC? during TLR signaling. CHIP-mediated enhancement of TLR signaling is inhibited by IFNAR deficiency or expression of ubiquitination resistant mutant forms of Src or PKC?. These findings suggest that CHIP facilitates the formation of a TLR signaling complex by recruiting, ubiquitinating, and activating Src and PKC?.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CHIP protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/HSC70 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-7,
http://linkedlifedata.com/resource/pubmed/chemical/Irf3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Irf7 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/STUB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 9,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C zeta,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1540-9538
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
26
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pubmed:volume |
208
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2099-112
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pubmed:meshHeading |
pubmed-meshheading:21911421-Animals,
pubmed-meshheading:21911421-Cell Line,
pubmed-meshheading:21911421-Enzyme Activation,
pubmed-meshheading:21911421-Gene Knockdown Techniques,
pubmed-meshheading:21911421-HSC70 Heat-Shock Proteins,
pubmed-meshheading:21911421-Humans,
pubmed-meshheading:21911421-Immunity, Innate,
pubmed-meshheading:21911421-Interferon Regulatory Factor-3,
pubmed-meshheading:21911421-Interferon Regulatory Factor-7,
pubmed-meshheading:21911421-Mice,
pubmed-meshheading:21911421-Mice, Inbred C57BL,
pubmed-meshheading:21911421-Mice, Knockout,
pubmed-meshheading:21911421-NF-kappa B,
pubmed-meshheading:21911421-Protein Kinase C,
pubmed-meshheading:21911421-Signal Transduction,
pubmed-meshheading:21911421-Toll-Like Receptor 4,
pubmed-meshheading:21911421-Toll-Like Receptor 9,
pubmed-meshheading:21911421-Ubiquitin-Protein Ligases,
pubmed-meshheading:21911421-Ubiquitination,
pubmed-meshheading:21911421-src-Family Kinases
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pubmed:year |
2011
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pubmed:articleTitle |
E3 ubiquitin ligase CHIP facilitates Toll-like receptor signaling by recruiting and polyubiquitinating Src and atypical PKC{zeta}.
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pubmed:affiliation |
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai200433, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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