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

Rebsamen, Manuele, Heinz, Leonhard X., Meylan, Etienne, Michallet, Marie-Cecile, Schroder, Kate, Hofmann, Kay, Vazquez, Jessica, Benedict, Chris A. and Tschopp, Jurg (2009) DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-κB. EMBO Reports, 10 8: 916-922. doi:10.1038/embor.2009.109

Author Rebsamen, Manuele
Heinz, Leonhard X.
Meylan, Etienne
Michallet, Marie-Cecile
Schroder, Kate
Hofmann, Kay
Vazquez, Jessica
Benedict, Chris A.
Tschopp, Jurg
Title DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-κB
Journal name EMBO Reports   Check publisher's open access policy
ISSN 1469-221X
Publication date 2009-08
Sub-type Article (original research)
DOI 10.1038/embor.2009.109
Volume 10
Issue 8
Start page 916
End page 922
Total pages 7
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
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-κB) 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-κB 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-κB 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-κB 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-κB and suggest a possible new immune modulation strategy of the MCMV.
Keyword NF-kappaB
Type I interferon
DNA sensor
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 96 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 02 Feb 2011, 17:20:26 EST by Dr Kate Schroder on behalf of Institute for Molecular Bioscience