The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
MLKL Activation Triggers NLRP3-Mediated Processing and Release of IL-1β Independently of Gasdermin-D
Open accessAbstract
Necroptosis is a form of programmed cell death defined by activation of the kinase receptor interacting protein kinase 3 and its downstream effector, the pseudokinase mixed lineage kinase domain-like (MLKL). Activated MLKL translocates to the cell membrane and disrupts it, leading to loss of cellular ion homeostasis. In this study, we use a system in which this event can be specifically triggered by a small-molecule ligand to show that MLKL activation is sufficient to induce the processing and release of bioactive IL-1β. MLKL activation triggers potassium efflux and assembly of the NLRP3 inflammasome, which is required for the processing and activity of IL-1β released during necroptosis. Notably, MLKL activation also causes cell membrane disruption, which allows efficient release of IL-1β independently of the recently described pyroptotic effector gasdermin-D. Taken together, our findings indicate that MLKL is an endogenous activator of the NLRP3 inflammasome, and that MLKL activation provides a mechanism for concurrent processing and release of IL-1β independently of gasdermin-D.
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Cites
Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling
Kayagaki, N., Stowe, I. B., Lee, B. L., O’Rourke, K., Anderson, K., Warming, S., Cuellar, T., Haley, B., Roose-Girma, M., Phung, Q. T., et al. (2015) · Nature · doi:10.1038/nature15541 · Cited by 3,686
Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores
Liu, X., Zhang, Z., Ruan, J., Pan, Y., Magupalli, V. G., Wu, H., & Lieberman, J. (2016) · Nature · doi:10.1038/nature18629 · Cited by 3,202
Cryopyrin activates the inflammasome in response to toxins and ATP
Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., & Dixit, V. M. (2006) · Nature · doi:10.1038/nature04515 · Cited by 3,080
Pore-forming activity and structural autoinhibition of the gasdermin family
Ding, J., Wang, K., Liu, W., She, Y., Sun, Q., Shi, J., Sun, H., Wang, D.-C., & Shao, F. (2016) · Nature · doi:10.1038/nature18590 · Cited by 2,771
Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis
Cai, Z., Jitkaew, S., Zhao, J., Chiang, H.-C., Choksi, S., Liu, J., Ward, Y., Wu, L.-G., & Liu, Z.-G. (2014) · Nature Cell Biology · doi:10.1038/ncb2883 · Cited by 1,322
Linkermann, A., & Green, D. R. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1310050 · Cited by 1,103
Inhibitor of Apoptosis Proteins Limit RIP3 Kinase-Dependent Interleukin-1 Activation
Vince, J. E., Wong, W. W.-L., Gentle, I., Lawlor, K. E., Allam, R., O'Reilly, L., Mason, K., Gross, O., Ma, S., Guarda, G., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.012 · Cited by 491
Caspase-8 Blocks Kinase RIPK3-Mediated Activation of the NLRP3 Inflammasome
Kang, T.-B., Yang, S.-H., Toth, B., Kovalenko, A., & Wallach, D. (2013) · Immunity · doi:10.1016/j.immuni.2012.09.015 · Cited by 419
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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
Pyroptosis versus necroptosis: similarities, differences, and crosstalk
Frank, D., & Vince, J. E. (2019) · Cell Death & Differentiation · doi:10.1038/s41418-018-0212-6 · Cited by 1,062
Tong, X., Tang, R., Xiao, M., Xu, J., Wang, W., Zhang, B., Liu, J., Yu, X., & Shi, S. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01392-3 · Cited by 883
Pyroptosis in inflammatory diseases and cancer
Rao, Z., Zhu, Y., Yang, P., Chen, Z., Xia, Y., Qiao, C., Liu, W., Deng, H., Li, J., Ning, P., et al. (2022) · Theranostics · doi:10.7150/thno.71086 · Cited by 800
Initiation and execution mechanisms of necroptosis: an overview
Grootjans, S., Vanden Berghe, T., & Vandenabeele, P. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.65 · Cited by 566
Metadata
- Authors
- Gutierrez, K. D., Davis, M. A., Daniels, B. P., Olsen, T. M., Ralli-Jain, P., Tait, S. W. G., Gale, M., & Oberst, A.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-03-01
- Volume
- 198
- Issue
- 5
- Pages
- 2156-2164
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2580681278
- Cited by
- 228
- References
- 9
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: MLKL Activation Triggers NLRP3-Mediated Processing and Release of IL-1β Independently of Gasdermin-D. https://app.cochat.ai/papers/10.4049/jimmunol.1601757
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- Gutierrez, K. D., Davis, M. A., Daniels, B. P., Olsen, T. M., Ralli-Jain, P., Tait, S. W. G., Gale, M., & Oberst, A. (2017). MLKL Activation Triggers NLRP3-Mediated Processing and Release of IL-1β Independently of Gasdermin-D. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1601757
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