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PMID: 19667203 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

XIAP mediates NOD signaling via interaction with RIP2.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 106 ·No. 34 ·2009-08-25 ·Pages 14524-9

Krieg A, Correa RG, Garrison JB, Le Negrate G, Welsh K, Huang Z, Knoefel WT, Reed JC

Abstract

NOD1 and NOD2 are members of the NOD-like receptor (NLR) protein family that are involved in sensing the presence of pathogens and are a component of the innate immune system. Upon activation by specific bacterial peptides derived from peptidoglycans, NODs interact via a CARD-CARD interaction with the receptor-interacting protein kinase RIP2, an inducer of NF-kappaB activation. In this report, we show that NOD signaling is dependent on XIAP, a member of the inhibitor of apoptosis protein (IAP) family. Cells deficient in XIAP exhibit a marked reduction in NF-kappaB activation induced by microbial NOD ligands and by over-expression of NOD1 or NOD2. Moreover, we show that XIAP interacts with RIP2 via its BIR2 domain, which could be disrupted by XIAP antagonists SMAC and SMAC-mimicking compounds. Both NOD1 and NOD2 associated with XIAP in a RIP2-dependent manner, providing evidence that XIAP associates with the NOD signalosome. Taken together, our data suggest a role for XIAP in regulating innate immune responses by interacting with NOD1 and NOD2 through interaction with RIP2.

MeSH Terms
Cell Line Cell Line, Tumor Enzyme-Linked Immunosorbent Assay Gene Expression Green Fluorescent Proteins/genetics,metabolism HCT116 Cells Humans Immunoblotting Immunoprecipitation Interleukin-8/metabolism Luciferases/genetics,metabolism Mutation NF-kappa B/genetics,metabolism Nod1 Signaling Adaptor Protein/genetics,metabolism Nod2 Signaling Adaptor Protein/genetics,metabolism Protein Binding RNA, Small Interfering/genetics Receptor-Interacting Protein Serine-Threonine Kinase 2/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Transfection X-Linked Inhibitor of Apoptosis Protein/genetics,metabolism
Chemicals
Interleukin-8 NF-kappa B NOD1 protein, human NOD2 protein, human Nod1 Signaling Adaptor Protein Nod2 Signaling Adaptor Protein RNA, Small Interfering Recombinant Fusion Proteins X-Linked Inhibitor of Apoptosis Protein XIAP protein, human Green Fluorescent Proteins Luciferases RIPK2 protein, human Receptor-Interacting Protein Serine-Threonine Kinase 2
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Krieg Andreas
Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Correa Ricardo G
Garrison Jason B
Le Negrate Gaëlle
Welsh Kate
Huang Ziwei
Knoefel Wolfram T
Reed John C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0907131106
Published
2009-08-25
Epub
2009-00-10
Pages
14524-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2732880
Subset
IM
Grants
NIAID NIH HHS · R01 AI056324 · United States
NIAID NIH HHS · AI-56324 · United States
External Links
PubMed source DOI: 10.1073/pnas.0907131106 PMC Full Text View journal details
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