The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Ubiquitin-Induced Oligomerization of the RNA Sensors RIG-I and MDA5 Activates Antiviral Innate Immune Response
Open accessAbstract
SUMMARY RIG-I and MDA5 detect viral RNA in the cytoplasm and activate signaling cascades leading to the production of type-I interferons. RIG-I is activated through sequential binding of viral RNA and unanchored lysine-63 (K63) polyubiquitin chains, but how polyubiquitin activates RIG-I and whether MDA5 is activated through a similar mechanism remain unresolved. Here we showed that the CARD domains of MDA5 bound to K63 polyubiquitin and that this binding was essential for MDA5 to activate the transcription factor IRF3. Mutations of conserved residues in MDA5 and RIG-I that disrupt their ubiquitin binding also abrogated their ability to activate IRF3. Polyubiquitin binding induced the formation of a large complex consisting of four RIG-I and four ubiquitin chains. This hetero-tetrameric complex was highly potent in activating the antiviral signaling cascades. These results suggest a unified mechanism of RIG-I and MDA5 activation and reveal a unique mechanism by which ubiquitin regulates cell signaling and immune response.
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Cites
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., et al. (2006) · Nature · doi:10.1038/nature04734 · Cited by 3,888
Toll-like receptors and their crosstalk with other innate receptors in infection and immunity
Kawai, T., & Akira, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.05.006 · Cited by 3,658
RIGorous Detection: Exposing Virus Through RNA Sensing
Rehwinkel, J., & Reis e Sousa, C. (2010) · Science · doi:10.1126/science.1185068 · Cited by 163
Cited by
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-citationCai, X., Chen, J., Xu, H., Liu, S., Jiang, Q.-X., Halfmann, R., & Chen, Z. J. (2014) · Cell · doi:10.1016/j.cell.2014.01.063 · Cited by 567
Self-citationBreaching Self-Tolerance to Alu Duplex RNA Underlies MDA5-Mediated Inflammation
Ahmad, S., Mu, X., Yang, F., Greenwald, E., Park, J. W., Jacob, E., Zhang, C.-Z., & Hur, S. (2018) · Cell · doi:10.1016/j.cell.2017.12.016 · Cited by 449
Double-Stranded RNA Sensors and Modulators in Innate Immunity
Hur, S. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041356 · Cited by 420
Wang, Q., Liu, X., Cui, Y., Tang, Y., Chen, W., Li, S., Yu, H., Pan, Y., & Wang, C. (2014) · Immunity · doi:10.1016/j.immuni.2014.11.011 · Cited by 358
Metadata
- Authors
- Jiang, X., Kinch, L. N., Brautigam, C. A., Chen, X., Du, F., Grishin, N. V., & Chen, Z. J.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 36
- Issue
- 6
- Pages
- 959-973
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2080778613
- Cited by
- 406
- References
- 3
- FWCI
- 15.41
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Jiang, X., Kinch, L. N., Brautigam, C. A., Chen, X., Du, F., Grishin, N. V., & Chen, Z. J. (2012). Ubiquitin-Induced Oligomerization of the RNA Sensors RIG-I and MDA5 Activates Antiviral Innate Immune Response. Immunity. https://doi.org/10.1016/j.immuni.2012.03.022
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