DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB.

Details

Serval ID
serval:BIB_98489985CB9E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB.
Journal
EMBO reports
Author(s)
Rebsamen M., Heinz L.X., Meylan E., Michallet M.C., Schroder K., Hofmann K., Vazquez J., Benedict C.A., Tschopp J.
ISSN
1469-3178[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
10
Number
8
Pages
916-922
Language
english
Abstract
Detection of viral nucleic acids is central to antiviral immunity. Recently, DAI/ZBP1 (DNA-dependent activator of IRFs/Z-DNA binding protein 1) was identified as a cytoplasmic DNA sensor and shown to activate the interferon regulatory factor (IRF) and nuclear factor-kappa B (NF-kappaB) transcription factors, leading to type-I interferon production. DAI-induced IRF activation depends on TANK-binding kinase 1 (TBK1), whereas signalling pathways and molecular components involved in NF-kappaB activation remain elusive. Here, we report the identification of two receptor-interacting protein (RIP) homotypic interaction motifs (RHIMs) in the DAI protein sequence, and show that these domains relay DAI-induced NF-kappaB signals through the recruitment of the RHIM-containing kinases RIP1 and RIP3. We show that knockdown of not only RIP1, but also RIP3 affects DAI-induced NF-kappaB activation. Importantly, RIP recruitment to DAI is inhibited by the RHIM-containing murine cytomegalovirus (MCMV) protein M45. These findings delineate the DAI signalling pathway to NF-kappaB and suggest a possible new immune modulation strategy of the MCMV.
Keywords
Adaptor Proteins, Vesicular Transport/chemistry, Adaptor Proteins, Vesicular Transport/genetics, Animals, Binding Sites, Cell Line, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Glycoproteins/genetics, Glycoproteins/metabolism, Humans, Immunoblotting, Immunoprecipitation, Mice, NF-kappa B/metabolism, Nuclear Pore Complex Proteins/chemistry, Nuclear Pore Complex Proteins/genetics, Polymerase Chain Reaction, Protein Binding/genetics, Protein Binding/physiology, RNA-Binding Proteins/chemistry, RNA-Binding Proteins/genetics, Receptor-Interacting Protein Serine-Threonine Kinases/chemistry, Receptor-Interacting Protein Serine-Threonine Kinases/genetics
Pubmed
Web of science
Open Access
Yes
Create date
19/11/2009 15:45
Last modification date
20/08/2019 15:59
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