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Necroptosis-independent signaling by the RIP kinases in inflammation

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Abstract

Recent advances have identified a signaling cascade involving receptor interacting protein kinase 1 (RIPK1), RIPK3 and the pseudokinase mixed lineage kinase domain-like (MLKL) that is crucial for induction of necroptosis, a non-apoptotic form of cell death. RIPK1–RIPK3–MLKL-mediated necroptosis has been attributed to cause many inflammatory diseases through the release of cellular damage-associated molecular patterns (DAMPs). In addition to necroptosis, emerging evidence suggests that these necroptosis signal adaptors can also facilitate inflammation independent of cell death. In particular, the RIP kinases can drive NF-κB and inflammasome activation independent of cell death. In this review, we will discuss recent discoveries that led to this realization and present arguments why cell death-independent signaling by the RIP kinases may have a more important role in inflammation than necroptosis.

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Acknowledgments

This work is supported by NIH grant AI119030. F. K. M. C. is supported by a Senior Research Award from the Crohn’s & Colitis Foundation of America. K. M. was supported by fellowships from the Uehara Memorial Foundation and the Japan Society for the Promotion of Science.

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  1. Department of Pathology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA

    Kenta Moriwaki & Francis Ka-Ming Chan

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  1. Kenta Moriwaki
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Correspondence to Francis Ka-Ming Chan.

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Moriwaki, K., Chan, F.KM. Necroptosis-independent signaling by the RIP kinases in inflammation. Cell. Mol. Life Sci. 73, 2325–2334 (2016). https://doi.org/10.1007/s00018-016-2203-4

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