The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3
Open accessAbstract
TLR2 promotes NLRP3 inflammasome activation via an early MyD88-IRAK1-dependent pathway that provides a priming signal (signal 1) necessary for activation of the inflammasome by a second potassium-depleting signal (signal 2). Here we show that TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways. Both pathways require the scaffolding but not the catalytic function of caspase-8 or RIPK1. Only the late pathway requires kinase competent RIPK3 and MLKL function. Mechanistically, FADD/caspase-8 scaffolding function provides a post-translational signal 1 in the intermediate pathway, whereas in the late pathway it helps the oligomerization of RIPK3, which together with MLKL provides both signal 1 and 2 for inflammasome assembly. Cytoplasmic dsRNA activates NLRP3 independent of TRIF, RIPK1, RIPK3 or mitochondrial DRP1, but requires FADD/caspase-8 in wildtype macrophages to remove RIPK3 inhibition. Our study provides a comprehensive analysis of pathways that lead to NLRP3 inflammasome activation in response to dsRNA.
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Citations
Cites
Gout-associated uric acid crystals activate the NALP3 inflammasome
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Cryopyrin activates the inflammasome in response to toxins and ATP
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Self-citationCatalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
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Self-citationThe Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism
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Self-citationRIP3 mediates the embryonic lethality of caspase-8-deficient mice
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Self-citationToll-like Receptor 3-mediated Necrosis via TRIF, RIP3, and MLKL
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Self-citationRIPK1 Blocks Early Postnatal Lethality Mediated by Caspase-8 and RIPK3
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Self-citationInhibitor of Apoptosis Proteins Limit RIP3 Kinase-Dependent Interleukin-1 Activation
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“Given that FADD-or caspase-8 deficiency is embryonic lethal 19, 20, 21 and unleashes RIPK3-mediated necroptosis, we employed macrophages from either FADD/ RIPK3 or caspase-8/RIPK3 double knockout (DKO) mice 22, 23, 24 .”
Self-citationRIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition
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Self-citation
Cited by
NLRP3 inflammasome activation and cell death
Huang, Y., Xu, W., & Zhou, R. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-021-00740-6 · Cited by 1,527
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“In some experiments, cell culture supernatants were precipitated by methanol/chloroform as described previously 24,59 .”
Self-citationCaspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis
Fritsch, M., Günther, S. D., Schwarzer, R., Albert, M.-C., Schorn, F., Werthenbach, J. P., Schiffmann, L. M., Stair, N., Stocks, H., Seeger, J. M., et al. (2019) · Nature · doi:10.1038/s41586-019-1770-6 · Cited by 1,110
Necroptosis in development, inflammation and disease
Weinlich, R., Oberst, A., Beere, H. M., & Green, D. R. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.149 · Cited by 1,016
Self-citationAn update on the regulatory mechanisms of NLRP3 inflammasome activation
Paik, S., Kim, J. K., Silwal, P., Sasakawa, C., & Jo, E.-K. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-021-00670-3 · Cited by 892
Metadata
- Authors
- Kang, S., Fernandes-Alnemri, T., Rogers, C., Mayes, L., Wang, Y., Dillon, C., Roback, L., Kaiser, W., Oberst, A., Sagara, J., Fitzgerald, K. A., Green, D. R., Zhang, J., Mocarski, E. S., & Alnemri, E. S.
- Venue
- Nature Communications
- Published
- 2015-06-24
- Volume
- 6
- Issue
- 1
- Pages
- 7515-7515
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W1586591061
- Cited by
- 255
- References
- 16
- FWCI
- 10.68
- Type
- journal article
- Language
- en
- Open access
- gold
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