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The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.

RIP3 Induces Apoptosis Independent of Pronecrotic Kinase Activity

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Mandal, Pratyusha, Berger, Scott B., Pillay, Sirika, Moriwaki, Kenta, Huang, Chunzi, Guo, Hongyan, Lich, John D., Finger, Joshua, Kasparcova, Viera, Votta, Bart, Ouellette, Michael, King, Bryan W., Wisnoski, David, Lakdawala, Ami S., DeMartino, Michael P., Casillas, Linda N., Haile, Pamela A., Sehon, Clark A., Marquis, Robert W., Upton, Jason, Daley-Bauer, Lisa P., Roback, Linda, Ramia, Nancy, Dovey, Cole M., Carette, Jan E., Chan, Francis Ka-Ming, Bertin, John, Gough, Peter J., Mocarski, Edward S., Kaiser, William J.·2014·Molecular Cell
DOI 10.1016/j.molcel.2014.10.021
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Abstract

Summary Receptor interacting protein kinase 3 (RIP3 or RIPK3) has emerged as a central player in necroptosis and a potential target to control inflammatory disease. Here, three selective small molecule compounds are shown to inhibit RIP3 kinase-dependent necroptosis, although their therapeutic value is undermined by a surprising, concentration-dependent induction of apoptosis. These compounds interact with RIP3 to activate caspase 8 (Casp8) via RHIM-driven recruitment of RIP1 (RIPK1) to assemble a Casp8-FADD-cFLIP complex completely independent of pro-necrotic kinase activities and MLKL. RIP3 kinase-dead D161N mutant induces spontaneous apoptosis independent of compound; whereas, D161G, D143N, and K51A mutants only trigger apoptosis when compound is present. Accordingly, RIP3-K51A mutant mice (Rip3K51A/K51A) are viable and fertile, in stark contrast to the perinatal lethality of Rip3D161N/D161N mice. RIP3 therefore holds both necroptosis and apoptosis in balance through a Ripoptosome-like platform. This work highlights a common mechanism unveiling RHIM-driven apoptosis by therapeutic or genetic perturbation of RIP3.

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Cites

Show all 13 references

Research works printed but not linked: 28

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Metadata

Authors
Mandal, P., Berger, S. B., Pillay, S., Moriwaki, K., Huang, C., Guo, H., Lich, J. D., Finger, J., Kasparcova, V., Votta, B., Ouellette, M., King, B. W., Wisnoski, D., Lakdawala, A. S., DeMartino, M. P., Casillas, L. N., Haile, P. A., Sehon, C. A., Marquis, R. W., Upton, J., Daley-Bauer, L. P., Roback, L., Ramia, N., Dovey, C. M., Carette, J. E., Chan, F. K.-M., Bertin, J., Gough, P. J., Mocarski, E. S., & Kaiser, W. J.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2014-11
Volume
56
Issue
4
Pages
481-495
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2014.10.021
OpenAlex
W2169820248
Cited by
618
References
13
FWCI
17.16
Type
journal article
Language
en
Open access
bronze
Licence
Funders
  • National Institutes of Health (DP1 OD012198, GM112547, R01 AI020211, R01 AI083497, S10 1 S10 RR025679 01)
  • GlaxoSmithKline

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CoChat. (2026). Citation check: RIP3 Induces Apoptosis Independent of Pronecrotic Kinase Activity. https://app.cochat.ai/papers/10.1016/j.molcel.2014.10.021
The paper
Mandal, P., Berger, S. B., Pillay, S., Moriwaki, K., Huang, C., Guo, H., Lich, J. D., Finger, J., Kasparcova, V., Votta, B., Ouellette, M., King, B. W., Wisnoski, D., Lakdawala, A. S., DeMartino, M. P., Casillas, L. N., Haile, P. A., Sehon, C. A., Marquis, R. W., . . . Kaiser, W. J. (2014). RIP3 Induces Apoptosis Independent of Pronecrotic Kinase Activity. Molecular Cell. https://doi.org/10.1016/j.molcel.2014.10.021

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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