The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Reconstitution of the RIG-I Pathway Reveals a Signaling Role of Unanchored Polyubiquitin Chains in Innate Immunity
Open accessAbstract
SUMMARY RIG-I detects invading viral RNA and activates the transcription factors NF-κB and IRF3 through the mitochondrial protein MAVS. Here we show that RNA bearing 5′-triphosphate strongly activates the RIG-I–IRF3 signaling cascade in a reconstituted system composed of RIG-I, mitochondria and cytosol. Activation of RIG-I requires not only RNA, but also polyubiquitin chains linked through lysine-63 (K63) of ubiquitin. RIG-I binds specifically to K63 polyubiquitin chains through its tandem CARD domains in a manner that depends on RNA and ATP. Mutations in the CARD domains that abrogate ubiquitin binding also impair RIG-I activation. Remarkably, unanchored K63 ubiquitin chains, which are not conjugated to any target protein, potently activate RIG-I. These ubiquitin chains function as an endogenous ligand of RIG-I in human cells. Our results delineate the mechanism of RIG-I activation, identify CARD domains as a new ubiquitin sensor, and demonstrate that unanchored K63 polyubiquitin chains are signaling molecules in antiviral innate immunity.
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Self-citationIPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
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Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
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RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates
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Cited by
Komander, D., & Rape, M. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060310-170328 · Cited by 3,679
Crosstalk in NF-κB Signaling Pathways
Oeckinghaus, A., Hayden, M. S., & Ghosh, S. (2011) · Nature Immunology · doi:10.1038/ni.2065 · Cited by 1,942
Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation
Liu, S., Cai, X., Wu, J., Cong, Q., Chen, X., Li, T., Du, F., Ren, J., Wu, Y.-T., Grishin, N. V., et al. (2015) · Science · doi:10.1126/science.aaa2630 · Cited by 1,927
Self-citationImmune Signaling by RIG-I-like Receptors
Loo, Y.-M., & Gale, M. (2011) · Immunity · doi:10.1016/j.immuni.2011.05.003 · Cited by 1,875
NF-κB, the first quarter-century: remarkable progress and outstanding questions
Hayden, M. S., & Ghosh, S. (2012) · Genes & Development · doi:10.1101/gad.183434.111 · Cited by 1,693
Metadata
- Authors
- Zeng, W., Sun, L., Jiang, X., Chen, X., Hou, F., Adhikari, A., Xu, M., & Chen, Z. J.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 141
- Issue
- 2
- Pages
- 315-330
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2068518836
- Cited by
- 615
- References
- 6
- FWCI
- 19.67
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Zeng, W., Sun, L., Jiang, X., Chen, X., Hou, F., Adhikari, A., Xu, M., & Chen, Z. J. (2010). Reconstitution of the RIG-I Pathway Reveals a Signaling Role of Unanchored Polyubiquitin Chains in Innate Immunity. Cell. https://doi.org/10.1016/j.cell.2010.03.029
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