Initiation and execution mechanisms of necroptosis: an overview
Open accessAbstract
Necroptosis is a form of regulated cell death, which is induced by ligand binding to TNF family death domain receptors, pattern recognizing receptors and virus sensors. The common feature of these receptor systems is the implication of proteins, which contain a receptor interaction protein kinase (RIPK) homology interaction motif (RHIM) mediating recruitment and activation of receptor-interacting protein kinase 3 (RIPK3), which ultimately activates the necroptosis executioner mixed lineage kinase domain-like (MLKL). In case of the TNF family members, the initiator is the survival- and cell death-regulating RIPK1 kinase, in the case of Toll-like receptor 3/4 (TLR3/4), a RHIM-containing adaptor, called TRIF, while in the case of Z-DNA-binding protein ZBP1/DAI, the cytosolic viral sensor itself contains a RHIM domain. In this review, we discuss the different protein complexes that serve as nucleation platforms for necroptosis and the mechanism of execution of necroptosis. Transgenic models (knockout, kinase-dead knock-in) and pharmacologic inhibition indicate that RIPK1, RIPK3 or MLKL are implicated in many inflammatory, degenerative and infectious diseases. However, the conclusion of necroptosis being solely involved in the etiology of diseases is blurred by the pleiotropic roles of RIPK1 and RIPK3 in other cellular processes such as apoptosis and inflammasome activation.
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Activation of RIPK3 downstream of TNFR1 ligation relies on formation of RIPK1-containing and RIPK3-containing amyloid-like signaling complex known as necrosome, wherein first RIPK1 and then RIPK3 undergo trans-phosphorylation or auto-phosphorylation events required for MLKL recruitment and necroptosis activation.
“In particular, the activation of RIPK3 downstream of TNFR1 ligation relies on the formation of a RIPK1-containing and RIPK3-containing amyloid-like signaling complex commonly known as necrosome [436, 470], wherein first RIPK1 and then RIPK3 undergo a series of trans-phosphorylation or auto-phosphorylation events that are required for MLKL recruitment and necroptosis activation [437, 438, 442, 471]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [470]
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Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691 · see citing works
Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics
Kerr, J. F. R., Wyllie, A. H., & Currie, A. R. (1972) · British Journal of Cancer · doi:10.1038/bjc.1972.33 · Cited by 15,673 · see citing works
Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c
Liu, X., Kim, C. N., Yang, J., Jemmerson, R., & Wang, X. (1996) · Cell · doi:10.1016/s0092-8674(00)80085-9 · Cited by 5,167 · see citing works
Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N., Cuny, G. D., Mitchison, T. J., Moskowitz, M. A., & Yuan, J. (2005) · Nature Chemical Biology · doi:10.1038/nchembio711 · Cited by 3,068 · see citing works
Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes
Micheau, O., & Tschopp, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00521-x · Cited by 2,738 · see citing works
Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase
Sun, L., Wang, H., Wang, Z., He, S., Chen, S., Liao, D., Wang, L., Yan, J., Liu, W., Lei, X., et al. (2012) · Cell · doi:10.1016/j.cell.2011.11.031 · Cited by 2,698 · see citing works
Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion
He, W.-T., Wan, H., Hu, L., Chen, P., Wang, X., Huang, Z., Yang, Z.-H., Zhong, C.-Q., & Han, J. (2015) · Cell Research · doi:10.1038/cr.2015.139 · Cited by 2,517 · see citing works
Cho, Y., Challa, S., Moquin, D., Genga, R., Ray, T. D., Guildford, M., & Chan, F. K.-M. (2009) · Cell · doi:10.1016/j.cell.2009.05.037 · Cited by 2,435 · see citing works
Molecular mechanisms of necroptosis: an ordered cellular explosion
Vandenabeele, P., Galluzzi, L., Vanden Berghe, T., & Kroemer, G. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2970 · Cited by 2,382 · see citing works
Self-citationBoldin, M. P., Goncharov, T. M., Goltseve, Y. V., & Wallach, D. (1996) · Cell · doi:10.1016/s0092-8674(00)81265-9 · Cited by 2,292 · see citing works
Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009) · Cell · doi:10.1016/j.cell.2009.05.021 · Cited by 2,214 · see citing works
Necroptosis and its role in inflammation
Pasparakis, M., & Vandenabeele, P. (2015) · Nature · doi:10.1038/nature14191 · Cited by 2,148 · see citing works
Self-citationIdentification of RIP1 kinase as a specific cellular target of necrostatins
Degterev, A., Hitomi, J., Germscheid, M., Ch'en, I. L., Korkina, O., Teng, X., Abbott, D., Cuny, G. D., Yuan, C., Wagner, G., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.83 · Cited by 2,059 · see citing works
Hsu, H., Shu, H., Pan, M., & Goeddel, D. V. (1996) · Cell · doi:10.1016/s0092-8674(00)80984-8 · Cited by 1,998 · see citing works
Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Valitutti, S., Bodmer, J.-L., Schneider, P., Seed, B., & Tschopp, J. (2000) · Nature Immunology · doi:10.1038/82732 · Cited by 1,932 · see citing works
RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis
Zhang, D.-W., Shao, J., Lin, J., Zhang, N., Lu, B.-J., Lin, S.-C., Dong, M.-Q., & Han, J. (2009) · Science · doi:10.1126/science.1172308 · Cited by 1,931 · see citing works
Regulated necrosis: the expanding network of non-apoptotic cell death pathways
Berghe, T. V., Linkermann, A., Jouan-Lanhouet, S., Walczak, H., & Vandenabeele, P. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3737 · Cited by 1,735 · see citing works
Self-citationVaux, D. L., & Korsmeyer, S. J. (1999) · Cell · doi:10.1016/s0092-8674(00)80564-4 · Cited by 1,573 · see citing works
Wang, H., Sun, L., Su, L., Rizo, J., Liu, L., Wang, L., Wang, F., & Wang, X. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.003 · Cited by 1,564 · see citing works
Rogers, C., Fernandes-Alnemri, T., Mayes, L., Alnemri, D., Cingolani, G., & Alnemri, E. S. (2017) · Nature Communications · doi:10.1038/ncomms14128 · Cited by 1,510 · cited 1× · see citing works
“In this case, proteolytic cleavage of deafness-associated tumor supressor (DFNA5) by caspase-3 triggers secondary necrosis.(24) Figure 1 gives an overview of different types of regulated cell death, and of the core pathways involved in the initiation and execution of cell death.”
BackgroundTNF-α Induces Two Distinct Caspase-8 Activation Pathways
Wang, L., Du, F., & Wang, X. (2008) · Cell · doi:10.1016/j.cell.2008.03.036 · Cited by 1,352 · see citing works
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 · see citing works
Li, J., McQuade, T., Siemer, A. B., Napetschnig, J., Moriwaki, K., Hsiao, Y.-S., Damko, E., Moquin, D., Walz, T., McDermott, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.019 · Cited by 1,222 · see citing works
The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism
Murphy, J. M., Czabotar, P. E., Hildebrand, J. M., Lucet, I. S., Zhang, J.-G., Alvarez-Diaz, S., Lewis, R., Lalaoui, N., Metcalf, D., Webb, A. I., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.06.018 · Cited by 1,220 · see citing works
CELL DEATHS IN NORMAL VERTEBRATE ONTOGENY
Glucksmann, A. (1951) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.1951.tb00774.x · Cited by 1,208 · see citing works
Essential versus accessory aspects of cell death: recommendations of the NCCD 2015
Galluzzi, L., Bravo-San Pedro, J. M., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Alnemri, E. S., Altucci, L., Andrews, D., Annicchiarico-Petruzzelli, M., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.137 · Cited by 1,002 · see citing works
Self-citationHitomi, J., Christofferson, D. E., Ng, A., Yao, J., Degterev, A., Xavier, R. J., & Yuan, J. (2008) · Cell · doi:10.1016/j.cell.2008.10.044 · Cited by 989 · see citing works
Toll-like Receptor 3-mediated Necrosis via TRIF, RIP3, and MLKL
Kaiser, W. J., Sridharan, H., Huang, C., Mandal, P., Upton, J. W., Gough, P. J., Sehon, C. A., Marquis, R. W., Bertin, J., & Mocarski, E. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.462341 · Cited by 959 · see citing works
Vercammen, D., Beyaert, R., Denecker, G., Goossens, V., Loo, G., Declercq, W., Grooten, J., Fiers, W., & Vandenabeele, P. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.9.1477 · Cited by 925 · see citing works
Self-citationTumor necrosis factor can induce both apoptic and necrotic forms of cell lysis.
Laster, S. M., Wood, J. G., & Gooding, L. R. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.141.8.2629 · Cited by 909 · see citing works
Zhao, J., Jitkaew, S., Cai, Z., Choksi, S., Li, Q., Luo, J., & Liu, Z.-G. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200012109 · Cited by 901 · see citing works
Apaf1 (CED-4 Homolog) Regulates Programmed Cell Death in Mammalian Development
Cecconi, F., Álvarez-Bolado, G., Meyer, B. I., Roth, K. A., & Gruß, P. (1998) · Cell · doi:10.1016/s0092-8674(00)81732-8 · Cited by 894 · see citing works
Feoktistova, M., Geserick, P., Kellert, B., Panayotova‐Dimitrova, D., Langlais, C., Hupe, M., Cain, K., MacFarlane, M., Häcker, G. A., & Leverkus, M. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.011 · Cited by 855 · see citing works
Tenev, T., Bianchi, K., Darding, M., Broemer, M., Langlais, C., Wållberg, F., Zachariou, A., Lopez, J. S., MacFarlane, M., Cain, K., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.006 · Cited by 818 · see citing works
MLKL Compromises Plasma Membrane Integrity by Binding to Phosphatidylinositol Phosphates
Dondelinger, Y., Declercq, W., Montessuit, S., Roelandt, R., Gonçalves, A. C., Bruggeman, I., Hulpiau, P., Weber, K., Sehon, C. A., Marquis, R. W., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.04.026 · Cited by 812 · see citing works
Self-citationCaMKII is a RIP3 substrate mediating ischemia- and oxidative stress–induced myocardial necroptosis
Zhang, T., Zhang, Y., Cui, M., Jin, L., Wang, Y., Lv, F., Liu, Y., Zheng, W., Shang, H., Zhang, J., et al. (2016) · Nature Medicine · doi:10.1038/nm.4017 · Cited by 790 · see citing works
Chen, X., Li, W., Ren, J., Huang, D., He, W., Song, Y., Yang, C., Li, W., Zheng, X., Chen, P., et al. (2013) · Cell Research · doi:10.1038/cr.2013.171 · Cited by 778 · see citing works
Upton, J. W., Kaiser, W. J., & Mocarski, E. S. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.01.016 · Cited by 758 · see citing works
The morphology of various types of cell death in prenatal tissues
Schweichel, J. ‐., & Merker, H. ‐. (1973) · Teratology · doi:10.1002/tera.1420070306 · Cited by 738 · see citing works
He, S., Liang, Y., Shao, F., & Wang, X. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116302108 · Cited by 725 · see citing works
Antimicrobial peptides: linking partition, activity and high membrane-bound concentrations
Melo, M. N., Ferré, R., & Castanho, M. A. R. B. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2095 · Cited by 711 · see citing works
Converging roles of caspases in inflammasome activation, cell death and innate immunity
Man, S. M., & Kanneganti, T. (2015) · Nature reviews. Immunology · doi:10.1038/nri.2015.7 · Cited by 701 · see citing works
Activity of Protein Kinase RIPK3 Determines Whether Cells Die by Necroptosis or Apoptosis
Newton, K., Dugger, D. L., Wickliffe, K. E., Kapoor, N., de Almagro, M. C., Vucic, D., Komuves, L., Ferrando, R. E., French, D. M., Webster, J., et al. (2014) · Science · doi:10.1126/science.1249361 · Cited by 687 · see citing works
Apoptosis and necrosis: Detection, discrimination and phagocytosis
Krysko, D. V., Berghe, T. V., D'Herde, K. G. M. A., & Vandenabeele, P. (2008) · Methods · doi:10.1016/j.ymeth.2007.12.001 · Cited by 685 · see citing works
Self-citationRIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL
Lawlor, K. E., Khan, N. R., Mildenhall, A., Gerlic, M., Croker, B. A., D’Cruz, A. A., Hall, C. M., Spall, S. K., Anderton, H., Masters, S. L., et al. (2015) · Nature Communications · doi:10.1038/ncomms7282 · Cited by 643 · see citing works
RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8 + T cells
Yatim, N., Jusforgues-Saklani, H., Orozco, S. L., Schulz, O., da Silva, R. B., Sousa, C. R. E., Green, D. R., Oberst, A., & Albert, M. L. (2015) · Science · doi:10.1126/science.aad0395 · Cited by 625 · see citing works
Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD
Mizumura, K., Cloonan, S. M., Nakahira, K., Bhashyam, A. R., Cervo, M., Kitada, T., Glass, K., Owen, C. A., Mahmood, A., Washko, G. R., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74985 · Cited by 611 · see citing works
Hildebrand, J. M., Tanzer, M. C., Lucet, I. S., Young, S. N., Spall, S. K., Sharma, P., Pierotti, C., Garnier, J.-M., Dobson, R. C. J., Webb, A. I., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408987111 · Cited by 598 · see citing works
RIP Kinase-Dependent Necrosis Drives Lethal Systemic Inflammatory Response Syndrome
Duprez, L., Takahashi, N., Hauwermeiren, F. V., Vandendriessche, B., Goossens, V., Berghe, T. V., Declercq, W., Libert, C., Cauwels, A., & Vandenabeele, P. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.020 · Cited by 591 · see citing works
Self-citationTwo independent pathways of regulated necrosis mediate ischemia–reperfusion injury
Linkermann, A., Bräsen, J. H., Darding, M., Jin, M. K., Sanz, A. B., Heller, J.-O., Zen, F. D., Weinlich, R., Ortíz, A., Walczak, H., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305538110 · Cited by 568 · see citing works
Virus Inhibition of RIP3-Dependent Necrosis
Upton, J. W., Kaiser, W. J., & Mocarski, E. S. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.03.006 · Cited by 559 · see citing works
Dual Signaling of the Fas Receptor: Initiation of Both Apoptotic and Necrotic Cell Death Pathways
Vercammen, D., Brouckaert, G., Denecker, G., Van de Craen, M., Declercq, W., Fiers, W., & Vandenabeele, P. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.5.919 · Cited by 556 · see citing works
Self-citationNewton, K., Sun, X., & Dixit, V. M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.4.1464-1469.2004 · Cited by 544 · see citing works
Activation of Necroptosis in Multiple Sclerosis
Ofengeim, D., Ito, Y., Najafov, A., Zhang, Y., Shan, B., DeWitt, J. P., Ye, J., Zhang, X., Chang, A., Vakifahmetoglu-Norberg, H., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.02.051 · Cited by 526 · see citing works
Koo, G.-B., Morgan, M. J., Lee, D., Kim, W.-J., Yoon, J.-H., Koo, J. S., Kim, S. H., Kim, S., Son, M. K., Hong, S. S., et al. (2015) · Cell Research · doi:10.1038/cr.2015.56 · Cited by 489 · see citing works
Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner
Conos, S. A., Chen, K. W., De Nardo, D., Hara, H., Whitehead, L., Núñez, G., Masters, S. L., Murphy, J. M., Schroder, K., Vaux, D. L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1613305114 · Cited by 485 · see citing works
RIP1, a kinase on the crossroads of a cell's decision to live or die
Festjens, N., Berghe, T. V., Cornelis, S., & Vandenabeele, P. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402085 · Cited by 467 · see citing works
Self-citationTakahashi, N., Duprez, L., Grootjans, S., Cauwels, A., Nerinckx, W., DuHadaway, J. B., Goossens, V, Roelandt, R., Van Hauwermeiren, F., Libert, C., et al. (2012) · Cell Death & Disease · doi:10.1038/cddis.2012.176 · Cited by 465 · see citing works
Self-citationLinkermann, A., Bräsen, J. H., Himmerkus, N., Liu, S., Huber, T. B., Kunzendorf, U., & Krautwald, S. (2012) · Kidney International · doi:10.1038/ki.2011.450 · Cited by 462 · see citing works
Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis
Wu, J., Huang, Z., Ren, J., Zhang, Z., He, P., Li, Y., Ma, J., Chen, W., Zhang, Y., Zhou, X., et al. (2013) · Cell Research · doi:10.1038/cr.2013.91 · Cited by 452 · see citing works
Parthanatos, a messenger of death
David, K. K. (2009) · Frontiers in Bioscience · doi:10.2741/3297 · Cited by 450 · see citing works
Newton, K., Dugger, D. L., Maltzman, A., Greve, J. M., Hedehus, M., Martin-McNulty, B., Carano, R. A. D., Cao, T. C., van Bruggen, N., Bernstein, L., et al. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.46 · Cited by 442 · see citing works
Dondelinger, Y., Jouan-Lanhouet, S., Divert, T., Theatre, E., Bertin, J., Gough, P. J., Giansanti, P., Heck, A. J. R., Dejardin, E., Vandenabeele, P., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.07.032 · Cited by 431 · see citing works
Self-citationRIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation
Lin, J., Kumari, S., Kim, C., Van, T.-M., Wachsmuth, L., Polykratis, A., & Pasparakis, M. (2016) · Nature · doi:10.1038/nature20558 · Cited by 421 · see citing works
RIPK1 inhibits ZBP1-driven necroptosis during development
Newton, K., Wickliffe, K. E., Maltzman, A., Dugger, D. L., Strasser, A., Pham, V. C., Lill, J. R., Roose-Girma, M., Warming, S., Solon, M., et al. (2016) · Nature · doi:10.1038/nature20559 · Cited by 390 · see citing works
Kaiser, W. J., & Offermann, M. K. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.8.4942 · Cited by 374 · see citing works
Berger, S. B., Kasparcova, V., Hoffman, S., Swift, B., Dare, L., Schaeffer, M., Capriotti, C., Cook, M., Finger, J., Hughes-Earle, A., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400499 · Cited by 374 · see citing works
Sun, X., Yin, J., Starovasnik, M. A., Fairbrother, W. J., & Dixit, V. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109488200 · Cited by 371 · see citing works
DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF‐κB
Rebsamen, M., Heinz, L. X., Meylan, E., Michallet, M., Schroder, K., Hofmann, K., Vázquez, J., Benedict, C. A., & Tschopp, J. (2009) · EMBO Reports · doi:10.1038/embor.2009.109 · Cited by 365 · see citing works
Shikonin circumvents cancer drug resistance by induction of a necroptotic death
Han, W., Li, L., Qiu, S., Lu, Q., Pan, Q., Gu, Y., Luo, J., & Hu, X. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0511 · Cited by 364 · see citing works
Tata, J. R. (1966) · Developmental Biology · doi:10.1016/0012-1606(66)90050-9 · Cited by 361 · see citing works
TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation
Jouan-Lanhouet, S., Arshad, M. I., Piquet-Pellorce, C., Martin-Chouly, C., Le Moigne-Muller, G., Van Herreweghe, F., Takahashi, N., Sergent, O., Lagadic-Gossmann, D., Vandenabeele, P., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2012.90 · Cited by 357 · see citing works
Self-citationInterferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases
Thapa, R. J., Nogusa, S., Chen, P., Maki, J. L., Lerro, A., Andrake, M., Rall, G. F., Degterev, A., & Balachandran, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301218110 · Cited by 355 · see citing works
Programmed Necrosis in the Cross Talk of Cell Death and Inflammation
Chan, F. K.-M., Luz, N. F., & Moriwaki, K. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112248 · Cited by 350 · see citing works
Necrostatin: A Potentially Novel Cardioprotective Agent?
Smith, C., Davidson, S. M., Lim, S. Y., Simpkin, J. C., Hothersall, J. S., & Yellon, D. M. (2007) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-007-6035-1 · Cited by 330 · see citing works
Polykratis, A., Hermance, N. M., Zelic, M., Roderick, J. E., KIM, C. S., Van, T.-M., Lee, T. H., Chan, F. K.-M., Pasparakis, M., & Kelliher, M. A. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400590 · Cited by 328 · see citing works
Oerlemans, M. I. F. J., Liu, J., Arslan, F., den Ouden, K., van Middelaar, B. J., Doevendans, P. A., & Sluijter, J. P. G. (2012) · Basic Research in Cardiology · doi:10.1007/s00395-012-0270-8 · Cited by 326 · see citing works
Interdigital cell death can occur through a necrotic and caspase-independent pathway
Chautan, M., Chazal, G., Cecconi, F., Gruß, P., & Golstein, P. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80425-4 · Cited by 325 · see citing works
What is apoptosis, and why is it important? Education and debate
Renehan, A. G., Booth, C., & Potten, C. S. (2001) · BMJ · doi:10.1136/bmj.322.7301.1536 · Cited by 320 · see citing works
Unconventional Roles of the NADPH Oxidase: Signaling, Ion Homeostasis, and Cell Death
Steinberg, B. E., & Grinstein, S. (2007) · Science s STKE · doi:10.1126/stke.3792007pe11 · Cited by 319 · see citing works
Dondelinger, Y., Aguileta, M. A., Goossens, V, Dubuisson, C., Grootjans, S., Dejardin, E., Vandenabeele, P., & Bertrand, M. J. M. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2013.94 · Cited by 312 · see citing works
Self-citationChu‐Wang, I., & Oppenheim, R. W. (1978) · The Journal of Comparative Neurology · doi:10.1002/cne.901770105 · Cited by 311 · see citing works
Absence of receptor interacting protein kinase 3 prevents ethanol-induced liver injury
Roychowdhury, S., McMullen, M. R., Pisano, S. G., Liu, X., & Nagy, L. E. (2013) · Hepatology · doi:10.1002/hep.26200 · Cited by 304 · see citing works
Distinct roles of RIP1–RIP3 hetero- and RIP3–RIP3 homo-interaction in mediating necroptosis
Wu, X.-N., Yang, Z.-H., Wang, X.-K., Zhang, Y., Wan, H., Song, Y., Chen, X., Shao, J., & Han, J. (2014) · Cell Death & Differentiation · doi:10.1038/cdd.2014.77 · Cited by 299 · see citing works
RIPK1 both positively and negatively regulates RIPK3 oligomerization and necroptosis
Orozco, S., Yatim, N., Werner, M. R., Tran, H., Gunja, S. Y., Tait, S. W., Albert, M. L., Green, D. R., & Oberst, A. (2014) · Cell Death & Differentiation · doi:10.1038/cdd.2014.76 · Cited by 294 · see citing works
Pilar, G., & Landmesser, L. T. (1976) · The Journal of Cell Biology · doi:10.1083/jcb.68.2.339 · Cited by 266 · see citing works
Chen, W., Zhou, Z., Li, L., Zhong, C., Zheng, X., Wu, X., Zhang, Y., Ma, H., Huang, D., Li, W., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.435545 · Cited by 265 · see citing works
NEMO and RIP1 Control Cell Fate in Response to Extensive DNA Damage via TNF-α Feedforward Signaling
Biton, S., & Ashkenazi, A. (2011) · Cell · doi:10.1016/j.cell.2011.02.023 · Cited by 262 · see citing works
Ramachandran, A., McGill, M. R., Xie, Y., Ni, H., Ding, W., & Jaeschke, H. (2013) · Hepatology · doi:10.1002/hep.26547 · Cited by 258 · see citing works
Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3
Kang, S., Fernandes‐Alnemri, T., Rogers, C., Mayes, L., Wang, Y., Dillon, C. P., Roback, L., Kaiser, W. J., Oberst, A., Sagara, J., et al. (2015) · Nature Communications · doi:10.1038/ncomms8515 · Cited by 255 · see citing works
The Necroptosis Adaptor RIPK3 Promotes Injury-Induced Cytokine Expression and Tissue Repair
Moriwaki, K., Balaji, S., McQuade, T. J., Malhotra, N., Kang, J., & Chan, F. K.-M. (2014) · Immunity · doi:10.1016/j.immuni.2014.09.016 · Cited by 251 · see citing works
Intracellular regulation of TNF activity in health and disease
Varfolomeev, E. E., & Vucic, D. (2016) · Cytokine · doi:10.1016/j.cyto.2016.08.035 · Cited by 247 · see citing works
Moriwaki, K., Bertin, J., Gough, P. J., Orlowski, G. M., & Chan, F. K. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.16 · Cited by 244 · see citing works
Toward an understanding of the protein interaction network of the human liver
Wang, J., Huo, K., Ma, L., Tang, L., Li, D., Huang, X., Yuan, Y., Li, C., Wang, W., Guan, W., et al. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.67 · Cited by 243 · see citing works
Sequential Engagement of Distinct MLKL Phosphatidylinositol-Binding Sites Executes Necroptosis
Quarato, G., Guy, C. S., Grace, C. R., Llambi, F., Nourse, A., Rodríguez, D. A., Wakefield, R., Frase, S., Moldoveanu, T., & Green, D. R. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.01.011 · Cited by 242 · see citing works
MLKL Activation Triggers NLRP3-Mediated Processing and Release of IL-1β Independently of Gasdermin-D
Gutierrez, K. D., Davis, M. A., Daniels, B. P., Olsen, T. M., Ralli-Jain, P., Tait, S. W. G., Gale, M., & Oberst, A. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601757 · Cited by 229 · see citing works
Pierdomenico, M., Negroni, A., Stronati, L., Vitali, R., Prete, E., Bertin, J., Gough, P. J., Aloi, M., & Cucchiara, S. (2013) · The American Journal of Gastroenterology · doi:10.1038/ajg.2013.403 · Cited by 217 · see citing works
Programmed Cell Death of Developing Mammalian Neurons after Genetic Deletion of Caspases
Oppenheim, R. W., Flavell, R. A., Vinsant, S. L., Prevette, D. M., Kuan, C.-Y., & RAKIC, P. T. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-13-04752.2001 · Cited by 216 · see citing works
Basit, F., Cristofanon, S., & Fulda, S. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2013.45 · Cited by 211 · see citing works
A novel role for RIP1 kinase in mediating TNFα production
Christofferson, D. E., Li, Y., Hitomi, J., Zhou, W., Upperman, C., Zhu, H., Gerber, S. A., Gygi, S. P., & Yuan, J. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.64 · Cited by 211 · see citing works
Rajput, A., Kovalenko, A., Bogdanov, K., Yang, S., Kang, T., Kim, J., Du, J., & Wallach, D. (2011) · Immunity · doi:10.1016/j.immuni.2010.12.018 · Cited by 203 · see citing works
Upton, J. W., Kaiser, W. J., & Mocarski, E. S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.c800051200 · Cited by 202 · see citing works
Xia, B., Fang, S., Chen, X., Hu, H., Chen, P., Wang, H., & Gao, Z. (2016) · Cell Research · doi:10.1038/cr.2016.26 · Cited by 202 · see citing works
Structural Insights into RIP3-Mediated Necroptotic Signaling
Xie, T., Peng, W., Yan, C., Wu, J., Gong, X., & Shi, Y. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.08.044 · Cited by 192 · see citing works
Murakami, Y., Matsumoto, H., Roh, M., Giani, A., Kataoka, K., Morizane, Y., Kayama, M., Thanos, A., Nakatake, S., Notomi, S., et al. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.109 · Cited by 191 · see citing works
McComb, S., Cessford, E., Alturki, N. A., Joseph, J., Shutinoski, B., Startek, J. B., Gamero, A. M., Mossman, K. L., & Sad, S. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1407068111 · Cited by 190 · see citing works
Pearson, J. S., Giogha, C., Mühlen, S., Nachbur, U., Pham, C. L. L., Zhang, Y., Hildebrand, J. M., Oates, C. V. L., Lung, T. W. F., Ingle, D. J., et al. (2017) · Nature Microbiology · doi:10.1038/nmicrobiol.2016.258 · Cited by 184 · see citing works
Poly-ubiquitination in TNFR1-mediated necroptosis
Dondelinger, Y., Darding, M., Bertrand, M. J. M., & Walczak, H. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2191-4 · Cited by 173 · see citing works
Ashpole, N. M., Herren, A. W., Ginsburg, K. S., Brogan, J. D., Johnson, D. E., Cummins, T., Bers, D. M., & Hudmon, A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.322537 · Cited by 173 · see citing works
Absence of RIPK3 predicts necroptosis resistance in malignant melanoma
Geserick, P., Wang, J., Schilling, R., Horn, S., Harris, P. A., Bertin, J., Gough, P. J., Feoktistova, M., & Leverkus, M. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.240 · Cited by 168 · see citing works
Vandenabeele, P., Grootjans, S., Callewaert, N., & Takahashi, N. (2012) · Cell Death and Differentiation · doi:10.1038/cdd.2012.151 · Cited by 166 · see citing works
Self-citationGenetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma
Cerhan, J. R., Ansell, S. M., Fredericksen, Z. S., Kay, N. E., Liebow, M., Call, T. G., Doǧan, A., Cunningham, J. M., Wang, A. H., Liu‐Mares, W., et al. (2007) · Blood · doi:10.1182/blood-2007-05-088682 · Cited by 162 · see citing works
Ppm1b negatively regulates necroptosis through dephosphorylating Rip3
Chen, W., Wu, J., Li, L., Zhang, Z., Ren, J., Liang, Y., Chen, F., Yang, C., Zhou, Z., Sean Su, S., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3120 · Cited by 161 · see citing works
Necroptosis, in vivo detection in experimental disease models
Jouan-Lanhouet, S., Riquet, F. B., Duprez, L., Berghe, T. V., Takahashi, N., & Vandenabeele, P. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.08.010 · Cited by 160 · see citing works
Self-citationAn evolutionary perspective on the necroptotic pathway
Dondelinger, Y., Hulpiau, P., Saeys, Y., Bertrand, M. J. M., & Vandenabeele, P. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.06.004 · Cited by 159 · see citing works
Self-citationGünther, C., He, G.-W., Kremer, A. E., Murphy, J. M., Petrie, E. J., Amann, K., Vandenabeele, P., Linkermann, A., Poremba, C., Schleicher, U., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci87545 · Cited by 157 · see citing works
Self-citationZheng, L., Bidère, N., Staudt, D., Cubre, A., Orenstein, J. M., Chan, F. K.-M., & Lenardo, M. J. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.9.3505-3513.2006 · Cited by 155 · see citing works
Necroptosis is preceded by nuclear translocation of the signaling proteins that induce it
Yoon, S., Bogdanov, K., Kovalenko, A., & Wallach, D. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.92 · Cited by 150 · see citing works
Endoplasmic reticulum stress induces ligand-independent TNFR1-mediated necroptosis in L929 cells
Saveljeva, S., Laughlin, S. L. M., Vandenabeele, P., Samali, A., & Bertrand, M. J. M. (2015) · Cell Death and Disease · doi:10.1038/cddis.2014.548 · Cited by 149 · see citing works
Self-citationAntigen-mediated T cell expansion regulated by parallel pathways of death
Ch’en, I. L., Beisner, D. R., Degterev, A., Lynch, C., Yuan, J., Hoffmann, A., & Hedrick, S. Μ. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808043105 · Cited by 141 · see citing works
Nugues, A.-L., Bouazzati, H. E., Hétuin, D., Berthon, C., Loyens, A., Bertrand, E., Jouy, N., Idziorek, T., & Quesnel, B. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.347 · Cited by 136 · see citing works
Dichotomy between RIP1- and RIP3-Mediated Necroptosis in Tumor Necrosis Factor-α-Induced Shock
Linkermann, A., Bräsen, J. H., Zen, F. D., Weinlich, R., Schwendener, R. A., Green, D. R., Kunzendorf, U., & Krautwald, S. (2012) · Molecular Medicine · doi:10.2119/molmed.2011.00423 · Cited by 135 · see citing works
NF-κB Protects Cells from Gamma Interferon-Induced RIP1-Dependent Necroptosis
Thapa, R. J., Basagoudanavar, S. H., Nogusa, S., Irrinki, K. M., Mallilankaraman, K. B., Slifker, M. J., Beg, A. A., Madesh, M., & Balachandran, S. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05445-11 · Cited by 133 · see citing works
Kearney, C. J., Cullen, S. P., Tynan, G. A., Henry, C. M., Clancy, D. M., Lavelle, E. C., & Martin, S. J. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2014.222 · Cited by 132 · see citing works
The MLKL Channel in Necroptosis Is an Octamer Formed by Tetramers in a Dyadic Process
Huang, D., Zheng, X., Wang, Z.-A., Chen, X., He, W., Zhang, Y., Xu, J.-G., Zhao, H., Shi, W., Wang, X., et al. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.00497-16 · Cited by 132 · see citing works
Ca V 1.2 β-subunit coordinates CaMKII-triggered cardiomyocyte death and afterdepolarizations
Koval, O. M., Guan, X., Wu, Y., Joiner, M.-L. A., Gao, Z., Chen, B., Grumbach, I. M., Luczak, E. D., Colbran, R. J., Song, L., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913760107 · Cited by 130 · see citing works
Positive and negative phosphorylation regulates RIP1- and RIP3-induced programmed necrosis
McQuade, T. J., Cho, Y., & Chan, F. K.-M. (2013) · Biochemical Journal · doi:10.1042/bj20130860 · Cited by 129 · see citing works
Horvitz, H. R., Sternberg, P. W., Greenwald, I., Fixsen, W. D., & Ellis, H. M. (1983) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1983.048.01.050 · Cited by 127 · see citing works
Colbert, L. E., Fisher, S. B., Hardy, C. W., Hall, W. A., Saka, B., Shelton, J. W., Petrova, A. V., Warren, M. D., Pantazides, B. G., Gandhi, K., et al. (2013) · Cancer · doi:10.1002/cncr.28144 · Cited by 126 · see citing works
Abraham, M. C., Lu, Y., & Shaham, S. (2007) · Developmental Cell · doi:10.1016/j.devcel.2006.11.012 · Cited by 118 · see citing works
Coordinated ubiquitination and phosphorylation of RIP1 regulates necroptotic cell death
de Almagro, M. C., Goncharov, T., Izrael-Tomasevic, A., Duttler, S., Kist, M., Varfolomeev, E. E., Wu, X., Lee, W. P., Murray, J. M., Webster, J. D., et al. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.78 · Cited by 118 · see citing works
Accumulation of Cytosolic Calcium Induces Necroptotic Cell Death in Human Neuroblastoma
Nomura, M., Ueno, A., Saga, K., Fukuzawa, M., & Kaneda, Y. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1283 · Cited by 117 · see citing works
Zhu, F., He, L., Peng, K., Liu, Y., & Xiong, J. (2013) · OncoTargets and Therapy · doi:10.2147/ott.s52805 · Cited by 115 · see citing works
RIP3-mediated necrotic cell death accelerates systematic inflammation and mortality
Meng, L., Jin, W., & Wang, X. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1514730112 · Cited by 109 · see citing works
Microarray analysis of promoter methylation in lung cancers
Fukasawa, M., Kimura, M., Morita, S., Matsubara, K., Yamanaka, S., Endo, C., Sakurada, A., Sato, M., Kondo, T., Horii, A., et al. (2006) · Journal of Human Genetics · doi:10.1007/s10038-005-0355-4 · Cited by 106 · see citing works
Manipulation of apoptosis and necroptosis signaling by herpesviruses
Guo, H., Kaiser, W. J., & Mocarski, E. S. (2015) · Medical Microbiology and Immunology · doi:10.1007/s00430-015-0410-5 · Cited by 99 · see citing works
Manji, G. A., Hozak, R. R., LaCount, D. J., & Friesen, P. D. (1997) · Journal of Virology · doi:10.1128/jvi.71.6.4509-4516.1997 · Cited by 94 · see citing works
Kim, S. K., Kim, W., Yoon, J.-H., Ji, J., Morgan, M. J., Cho, H., Kim, Y. C., & Kim, Y. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2015.90 · Cited by 80 · see citing works
Regulation of Kv4.3 currents by Ca2+/calmodulin-dependent protein kinase II
Sergeant, G. P., Ohya, S., Reihill, J. A., Perrino, B. A., Amberg, G. C., Imaizumi, Y., Horowitz, B., Sanders, K. M., & Koh, S. D. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00293.2004 · Cited by 79 · see citing works
Ruan, J., Mei, L., Zhu, Q., Shi, G., & Wang, H. (2015) · PubMed Central · Cited by 79 · see citing works
Gaiha, G. D., McKim, K. J., Woods, M. W., Pertel, T., Rohrbach, J., Barteneva, N. S., Chin, C. R., Liu, D., Soghoian, D. Z., Cesa, K. T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.12.011 · Cited by 76 · see citing works
Ertao, Z., Jianhui, C., Wang, K., Ye, Z., Wu, H., Chuangqi, C., Changjiang, Q., Sile, C., Yulong, H., & Shirong, C. (2016) · Tumor Biology · doi:10.1007/s13277-016-5229-1 · Cited by 75 · see citing works
Towards a Genetic Definition of Cancer-Associated Inflammation
Prendergast, G. C., Metz, R. A., & Muller, A. J. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.091173 · Cited by 74 · see citing works
Akt Regulates TNFα Synthesis Downstream of RIP1 Kinase Activation during Necroptosis
McNamara, C. R., Ahuja, R., Osafo-Addo, A. D., Barrows, D., Kettenbach, A. N., Skidan, I. N., Teng, X., Cuny, G. D., Gerber, S. A., & Degterev, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056576 · Cited by 69 · see citing works
Chen, D., Li, X., Zhai, Z., & Shu, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108675200 · Cited by 59 · see citing works
Post-translational modifications as key regulators of TNF-induced necroptosis
Liu, X., Shi, F., Li, Y., Yu, X., Peng, S., Li, W., Luo, X., & Cao, Y. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.197 · Cited by 54 · see citing works
Silke, J., & Vince, J. E. (2016) · Current topics in microbiology and immunology · doi:10.1007/82_2016_507 · Cited by 45 · see citing works
Mechanisms of RIPK3‐induced inflammation
Shlomovitz, I., Zargrian, S., & Gerlic, M. (2016) · Immunology and Cell Biology · doi:10.1038/icb.2016.124 · Cited by 42 · see citing works
RIPK1 prevents aberrant ZBP1-initiated necroptosis
Berghe, T. V., & Kaiser, W. J. (2016) · Oncotarget · doi:10.18632/oncotarget.13926 · Cited by 29 · see citing works
Regulation of RIPK1's cell death function by phosphorylation
Dondelinger, Y., Vandenabeele, P., & Bertrand, M. J. M. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1112688 · Cited by 26 · see citing works
Self-citationAdherence and fusion between the extremities of adjacent embryonic sacs in the pig.
Ashdown, R. R., & Marrable, A. W. (1967) · PubMed · Cited by 20 · see citing works
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- Renehan AG, Booth C, Potten CS. What is apoptosis, and why is it important? BMJ 2001; 322: 1536-1538.
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Self-citationPyroptosis 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 · see citing works
Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
Re, D. P. D., Amgalan, D., Linkermann, A., Liu, Q., & Kitsis, R. N. (2019) · Physiological Reviews · doi:10.1152/physrev.00022.2018 · Cited by 979 · see citing works
Targeting immunogenic cell death in cancer
Ahmed, A. S., & Tait, S. W. G. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12851 · Cited by 942 · see citing works
NINJ1 mediates plasma membrane rupture during lytic cell death
Kayagaki, N., Kornfeld, O. S., Lee, B. L., Stowe, I. B., O’Rourke, K., Li, Q., Sandoval, W., Yan, D., Kang, J., Xu, M., et al. (2021) · Nature · doi:10.1038/s41586-021-03218-7 · Cited by 857 · see citing works
Pattern Recognition Receptors and the Host Cell Death Molecular Machinery
Amarante-Mendes, G. P., Adjemian, S., Branco, L. M., Zanetti, L. C., Weinlich, R., & Bortoluci, K. R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02379 · Cited by 759 · see citing works
“However, in the absence of FADD, c-FLIP or a functional caspase-8, TNFRI signaling results in the recruitment of TRADD and RIPK1, forming a platform called complex IIb or necrosome, wherein RIPK3 and MLKL are activated to execute necroptosis (55).”
BackgroundCaspase-11–mediated endothelial pyroptosis underlies endotoxemia-induced lung injury
Cheng, K. T., Xiong, S., Ye, Z., Hong, Z., Di, A., Tsang, K. M., Gao, X., An, S., Mittal, M., Vogel, S. M., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci94495 · Cited by 472 · see citing works
“Necroptosislike pyroptosis is a lytic cell death mechanism mediated by kinases such as RIPK3 (27).”
BackgroundNecrotic, apoptotic and autophagic cell fates triggered by nanoparticles
Mohammadinejad, R., Moosavi, M. A., Tavakol, S., Vardar, D. Ö., Hosseini, A., Rahmati, M., Dini, L., Hussain, S., Mandegary, A., & Klionsky, D. J. (2018) · Autophagy · doi:10.1080/15548627.2018.1509171 · Cited by 464 · see citing works
“With regard to the TNF family members, the initiator is RIPK1; TICAM1/TRFI plays this role for TLR3 (toll like receptor 3)-TLR4, whereas for ZBP1/DAI (Z-DNA binding protein 1), there is a RIPK homology interaction motif domain within the cytosolic sensor [23].”
BackgroundApoptosis, Pyroptosis, and Necroptosis—Oh My! The Many Ways a Cell Can Die
Ketelut-Carneiro, N., & Fitzgerald, K. A. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167378 · Cited by 416 · see citing works
Myricetin: A review of the most recent research
Song, X., Tan, L., Wang, M., Ren, C., Guo, C., Yang, B., Ren, Y., Cao, Z., Li, Y., & Pei, J. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111017 · Cited by 387 · see citing works
Snyder, A. G., Hubbard, N., Messmer, M. N., Kofman, S. B., Hagan, C. E., Orozco, S. L., Chiang, K., Daniels, B. P., Baker, D. A., & Oberst, A. (2019) · Science Immunology · doi:10.1126/sciimmunol.aaw2004 · Cited by 372 · see citing works
Cell Death in the Origin and Treatment of Cancer
Strasser, A., & Vaux, D. L. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.05.014 · Cited by 370 · see citing works
Ferroptotic pores induce Ca2+ fluxes and ESCRT-III activation to modulate cell death kinetics
Pedrera, L., Espiritu, R. A., Ros, U., Weber, J., Schmitt, A. M., Stroh, J., Hailfinger, S., von Karstedt, S., & García‐Sáez, A. J. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00691-x · Cited by 320 · see citing works
“In necroptosis and pyroptosis, membrane permeabilization is mediated by dedicated protein cell-death effectors encoded in the genome (Chen et al., 2016, Grootjans et al., 2017, Sborgi et al., 2016).”
BackgroundCell Death Mechanisms in Cerebral Ischemia–Reperfusion Injury
Zhang, Q., Jia, M., Wang, Y., Wang, Q., & Wu, J. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03697-8 · Cited by 295 · see citing works
PANoptosis: A Unique Innate Immune Inflammatory Cell Death Modality
Nagakannan, P., & Kanneganti, T. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2200508 · Cited by 291 · see citing works
Necrostatin-1 and necroptosis inhibition: Pathophysiology and therapeutic implications
Cao, L., & Mu, W. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105297 · Cited by 269 · see citing works
“In the LPS-induced disease models of fulminant hepatic failure (FHF) and acute lung injury (ALI) [77,115], injection of LPS remarkably upregulated the expression and L. Cao and W. Mu Pharmacological Research 163 (2021) 105297 phosphorylation of RIP1 and RIP3, which was attenuated by Nec-1.”
BackgroundInfluentialInnate Immune Cell Death in Neuroinflammation and Alzheimer’s Disease
Rajesh, Y., & Kanneganti, T. (2022) · Cells · doi:10.3390/cells11121885 · Cited by 261 · see citing works
Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury
Jaeschke, H., & Ramachandran, A. (2024) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-051122-094016 · Cited by 272 · see citing works
Selective Targeting of TNF Receptors as a Novel Therapeutic Approach
Fischer, R., Kontermann, R. E., & Pfizenmaier, K. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00401 · Cited by 243 · see citing works
Copper in tumors and the use of copper-based compounds in cancer treatment
da Silva, D. A., Luca, A. D., Squitti, R., Rongioletti, M. C. A., Rossi, L. C., Machado, C. M. L., & Cerchiaro, G. (2021) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2021.111634 · Cited by 244 · see citing works
Iannielli, A., Bido, S., Folladori, L., Segnali, A., Cancellieri, C., Maresca, A., Massimino, L., Rubio, A., Morabito, G., Caporali, L., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.01.089 · Cited by 239 · see citing works
“Necroptosis is a regulated process of necrosis that is triggered by inflammatory signals and is dependent on the RIPK1/3 kinases (Grootjans et al., 2017).”
BackgroundOmega-3 docosahexaenoic acid induces pyroptosis cell death in triple-negative breast cancer cells
Pizato, N., Luzete, B. C., Kiffer, L. F. M. V., Corrêa, L. H., Santos, I. D. O., Assumpção, J. A. F., Ito, M., & Magalhães, K. G. (2018) · Scientific Reports · doi:10.1038/s41598-018-20422-0 · Cited by 224 · see citing works
The double-edged functions of necroptosis
Ye, K., Chen, Z., & Xu, Y. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05691-6 · Cited by 220 · see citing works
“However, NINJ1 is only partially involved in the release of lactate dehydrogenase (LDH, a standard measure of PMR) during MLKL-dependent necroptosis [15, 74].”
BackgroundLü, Z., Eeckhoutte, H. P. V., Liu, G., Nair, P. M., Jones, B., Gillis, C. M., Nalkurthi, B. C., Verhamme, F., Buyle-Huybrecht, T., Vandenabeele, P., et al. (2021) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202009-3442oc · Cited by 192 · see citing works
Self-citationDiscovery of Novel, Drug-Like Ferroptosis Inhibitors with in Vivo Efficacy
Devisscher, L., Coillie, S. V., Hofmans, S., Rompaey, D. V., Goossens, K., Meul, E., Maes, L. J. R. M., Winter, H. L. D., der Veken, P. V., Vandenabeele, P., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01299 · Cited by 179 · see citing works
Self-citationCell death regulation: A new way for natural products to treat osteoporosis
Li, Z., Li, D., Chen, R., Gao, S., Xu, Z., & Li, N. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106635 · Cited by 179 · see citing works
Chen, J., Kos, R., Garssen, J., & Redegeld, F. A. (2019) · Cells · doi:10.3390/cells8121486 · Cited by 178 · see citing works
“The necroptotic pathway is regulated by multiple steps of post-transcriptional modifications including phosphorylation and ubiquitination [5,6].”
BackgroundNecroptotic cell death in anti‐cancer therapy
Krysko, O., Aaes, T. L., Kagan, V. E., D'Herde, K. G. M. A., Bachert, C., Leybaert, L., Vandenabeele, P., & Krysko, D. V. (2017) · Immunological Reviews · doi:10.1111/imr.12583 · Cited by 174 · see citing works
Self-citationMLKL in cancer: more than a necroptosis regulator
Martens, S., Bridelance, J., Roelandt, R., Vandenabeele, P., & Takahashi, N. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-021-00785-0 · Cited by 174 · see citing works
“Once RIPK3 is activated, it phosphorylates the PsKD of MLKL (S345, S347, and T349 in mMLKL and T357/S358 in hMLKL), leading to a conformational change in the PsKD that unlocks the 4HB domain followed by a release of MLKL from the RIPK3 activation platform [20, 27, 28] (Fig.”
BackgroundSelf-citationNecroptosis in Immuno-Oncology and Cancer Immunotherapy
Sprooten, J., Wijngaert, P. D., Vanmeerbeek, I., Martin, S., Vangheluwe, P., Schlenner, S., Krysko, D. V., Parys, J. B., Bultynck, G., Vandenabeele, P., et al. (2020) · Cells · doi:10.3390/cells9081823 · Cited by 169 · see citing works
“This series of events can pave the way for apoptosis induction via a complex called cytosolic death-inducing signaling complex (DISC) (or complex IIa), mainly composed of RIPK1, TRADD, FAS-associated death domain protein (FADD) and procaspase-8, that can lead to caspase-8-driven extrinsic apoptosis (Figure 2) [82].”
BackgroundSelf-citationFueling the Fire: Inflammatory Forms of Cell Death and Implications for Cancer Immunotherapy
Rosenbaum, S. R., Wilski, N. A., & Aplin, A. E. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0805 · Cited by 172 · see citing works
Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity
Ma, W., Wei, S., Zhang, B., & Li, W. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00434 · Cited by 169 · see citing works
Koper, M. J., Schoor, E. V., Ospitalieri, S., Vandenberghe, R. R., Vandenbulcke, M., Arnim, C. A. F. V., Tousseyn, T., Balusu, S., Strooper, B. D., & Thal, D. R. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02103-y · Cited by 164 · see citing works
Schwarzer, R., Laurien, L., & Pasparakis, M. (2020) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2020.02.004 · Cited by 161 · see citing works
How do we fit ferroptosis in the family of regulated cell death?
Fearnhead, H. O., Vandenabeele, P., & Berghe, T. V. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.149 · Cited by 159 · see citing works
“membrane destabilizing mechanism has been discovered, that is, receptor interacting protein kinase (RIPK) 3-dependent phosphorylation of mixed lineage kinase domain-like (MLKL).(9,10) Similarly, we raise the question whether ferroptosis or oxytosis is only a consequence of insufficient cellular reduction capacity or d…”
BackgroundSelf-citationHaemoglobin scavenging in intracranial bleeding: biology and clinical implications
Bulters, D. O., Gaastra, B., Zolnourian, A. H., Alexander, S. A., Ren, D., Blackburn, S., Borsody, M. K., Doré, S., Galea, J. P., Iihara, K., et al. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0020-0 · Cited by 157 · see citing works
Realizing the Clinical Potential of Immunogenic Cell Death in Cancer Chemotherapy and Radiotherapy
Rapoport, B. L., & Anderson, R. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20040959 · Cited by 155 · see citing works
“In addition, activation of RIPK3 may also occur via interaction with the Z-DNA binding protein 1 (ZBP1), which operates as a sensor for cytosolic DNA-promoting type I interferon (IFN) synthesis, as well as NF-κB activation [40].”
BackgroundGudipaty, S. A., Conner, C. M., Rosenblatt, J., & Montell, D. J. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100616-060748 · Cited by 145 · see citing works
“…requires activation of the receptor-interacting kinases 1 and 3 (RIPK1 and -3) (Cho et al. 2009, Zhang et al. 2016), which results in the phosphorylation of the pseudokinase mixed lineage kinase– like (MLKL), causing its oligomerization and activation (Grootjans et al. 2017, Sun et al. 2012).”
BackgroundStringer, J. M., Alesi, L. R., Winship, A., & Hutt, K. J. (2023) · Human Reproduction Update · doi:10.1093/humupd/dmad005 · Cited by 145 · see citing works
“Importantly, these death receptors can also activate the extrinsic apoptosis pathway (Grootjans et al., 2017; Frank and Vince, 2019).”
BackgroundCell death in chronic inflammation: breaking the cycle to treat rheumatic disease
Anderton, H., Wicks, I. P., & Silke, J. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-0455-8 · Cited by 145 · see citing works
Caspase-11-mediated tubular epithelial pyroptosis underlies contrast-induced acute kidney injury
Zhang, Z., Shao, X., Jiang, N., Mou, S., Gu, L., Li, S., Lin, Q., He, Y., Zhang, M., Zhou, W., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-1023-x · Cited by 132 · see citing works
The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease
Oñate, M., Catenaccio, A., Salvadores, N., Saquel, C., Martinez, A. N., Moreno‐González, I., Gamez, N., Rudolffi-Soto, P., Soto, C. A., Hetz, C. A., et al. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0408-4 · Cited by 130 · see citing works
Yang, J., Zhao, Y., Zhang, L., Fan, H., Qi, C., Zhang, K., Liu, X., Fei, L., Chen, S., Wang, M., et al. (2018) · Cerebral Cortex · doi:10.1093/cercor/bhy089 · Cited by 129 · see citing works
“Upon stimulation of death signals, in cases where apoptotic signaling is inhibited, cells upregulate levels of receptor interacting protein kinase 1 (RIPK1) and receptor interacting protein kinase 3 (RIPK3), which activate a signaling cascade involving phosphorylation of the mixed lineage kinase domain-like protein (M…”
BackgroundThe role of apoptosis in acetaminophen hepatotoxicity
Jaeschke, H., Duan, L., Akakpo, J. Y., Farhood, A. I., & Ramachandran, A. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.06.025 · Cited by 129 · see citing works
“Necroptosis depends on the activation of receptor interacting serine/ threonine kinase 1(RIP1), RIP3 and mixed lineage kinase domain like pseudokinase (MLKL) (Grootjans et al., 2017).”
BackgroundInfluentialRegulated cell death: discovery, features and implications for neurodegenerative diseases
Cui, J., Zhao, S., Li, Y., Zhang, D., Wang, B., Xie, J., & Wang, J. (2021) · Cell Communication and Signaling · doi:10.1186/s12964-021-00799-8 · Cited by 125 · see citing works
“Transgenic models and pharmacologic inhibition have demonstrate that RIPK1, RIPK3 and MLKL are involved in many neurodegenerative diseases [198].”
BackgroundDAMPs in the immunogenicity of cell death
Chen, R., Zou, J., Liu, J., Kang, R., & Tang, D. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.09.007 · Cited by 124 · see citing works
Regulated Forms of Cell Death in Fungi
Gonçalves, A. P., Heller, J., Daskalov, A., Videira, A., & Glass, N. L. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01837 · Cited by 122 · see citing works
“The NLR-based amyloid signal transduction has been evolutionarily linked to a form of PCD in metazoans termed necroptosis (Daskalov et al., 2016; Grootjans et al., 2017).”
BackgroundGullett, J. M., Tweedell, R. E., & Kanneganti, T. (2022) · Cells · doi:10.3390/cells11091495 · Cited by 123 · see citing works
“Necroptosis can be initiated in response to the activation of toll-like receptors (TLRs), death receptors, or through interferon (IFN) signaling [65].”
Backgroundda Costa, L. S., Outlioua, A., Anginot, A., Akarid, K., & Arnoult, D. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1579-0 · Cited by 118 · see citing works
miR-425 deficiency promotes necroptosis and dopaminergic neurodegeneration in Parkinson’s disease
Hu, Y.-B., Zhang, Y., Wang, H., Ren, R., Cui, H., Huang, W., Cheng, Q., Chen, H., & Wang, G. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1809-5 · Cited by 118 · see citing works
Macías‐Rodríguez, R. U., Inzaugarat, M. E., Ruiz‐Margáin, A., Nelson, L. J., Trautwein, C., & Cubero, F. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051651 · Cited by 114 · see citing works
“Although necrosis was initially regarded as an essentially ‘disorganized’ cellular response, it has now been shown that there are specific pathways that regulate necroptosis, including a necrosis-like mode of regulated cell death [22].”
BackgroundInfluentialAutophagy Function and Regulation in Kidney Disease
Kaushal, G. P., Chandrashekar, K., Juncos, L. A., & Shah, S. V. (2020) · Biomolecules · doi:10.3390/biom10010100 · Cited by 111 · see citing works
HS-1371, a novel kinase inhibitor of RIP3-mediated necroptosis
Park, H.-H., Park, S.-Y., Mah, S., Park, J.-H., Hong, S.-S., Hong, S., & Kim, Y.-S. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0152-8 · Cited by 110 · see citing works
Comparing the effects of different cell death programs in tumor progression and immunotherapy
Messmer, M. N., Snyder, A. G., & Oberst, A. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0214-4 · Cited by 108 · see citing works
Redox biology of regulated cell death in cancer: A focus on necroptosis and ferroptosis
Florean, C., Song, S., Dicato, M. A., & Diederich, M. F. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.01.008 · Cited by 109 · see citing works
Fan, W., Guo, J., Gao, B., Zhang, W., Ling, L., Xu, T., Pan, C., Li, L., Chen, S., Wang, H., et al. (2019) · Science Signaling · doi:10.1126/scisignal.aaw3423 · Cited by 109 · see citing works
A decade of cell death studies: Breathing new life into necroptosis
Khan, I., Yousif, A., Chesnokov, M. S., Hong, L., & Chefetz, I. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107717 · Cited by 110 · see citing works
Interplay between Cell Death and Cell Proliferation Reveals New Strategies for Cancer Therapy
Loftus, L. V., Amend, S. R., & Pienta, K. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094723 · Cited by 112 · see citing works
“Additionally, animal studies suggest that necroptosis can compensate for apoptosis deficiencies in development, although clear distinctions from necrosis prevent definitive proof of this phenomenon [11].”
BackgroundMitochondrial transfer in tunneling nanotubes—a new target for cancer therapy
Guan, F., Wu, X., Zhou, J., Lin, Y., He, Y., Fan, C., Zeng, Z., & Xiong, W. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-03069-w · Cited by 111 · see citing works
“Recruited RIPK3, RIPK1, and MLKL proteins form the necrosome [100], after which MLKL forms pores in the cell membrane, ultimately leading to cell necroptosis [91].”
BackgroundYang, L. G., Sun, W. C., Du, J., Fan, J., & Peng, X. (2023) · JACS Au · doi:10.1021/jacsau.2c00591 · Cited by 105 · see citing works
Akimoto, M., Maruyama, R., Kawabata, Y., Tajima, Y., & Takenaga, K. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0851-z · Cited by 104 · see citing works
ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity
Yu, H., Yang, B., Yang, J., Shi, X., Yang, X., Zhang, D., Zhao, D., Yan, W., Chen, L., Zheng, H., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810224 · Cited by 105 · see citing works
Negroni, A., Colantoni, E., Pierdomenico, M., Palone, F., Costanzo, M., Oliva, S., Tiberti, A., Cucchiara, S., & Stronati, L. (2017) · Digestive and Liver Disease · doi:10.1016/j.dld.2017.08.017 · Cited by 103 · see citing works
“In conclusion, this study shows in vitro and ex vivo that RIP3 and MLKL have an active role in intestinal inflammation, by acting on multiple fronts: rising cytokine expression, promoting NF-kB 1208 A. Negroni et al. / Digestive and Liver Disease 49 (2017) 1201–1210 F ed m t ents a c n a d a ig.”
BackgroundInfluentialThe role of necroptosis in disease and treatment
Liu, X., Xie, X., Ren, Y., Shao, Z., Zhang, N., Li, L., Ding, X., & Zhang, L. (2021) · MedComm · doi:10.1002/mco2.108 · Cited by 103 · see citing works
Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)
Huang, Q., Le, Y., Li, S., & Bian, Y. (2024) · Respiratory Research · doi:10.1186/s12931-024-02678-5 · Cited by 103 · see citing works
“Subsequently, receptor-interacting protein kinase (RIPK) 1 and/or RIPK3 are recruited, leading to the activation of mixed lineage kinase domain-like protein (MLKL), which damages cell membrane integrity and induces necroptosis [151, 152].”
BackgroundWu, W., Wang, X., Sun, Y., Berleth, N., Deitersen, J., Schlütermann, D., Stuhldreier, F., Hieke, N., Mendiburo, M. J., Cox, J., et al. (2021) · Autophagy · doi:10.1080/15548627.2021.1899667 · Cited by 98 · see citing works
“, TNFRSF1A/ TNFR1 [TNF receptor superfamily member 1A]) is the best characterized form [31,32].”
BackgroundBuja, L. M. (2022) · Cardiology in Review · doi:10.1097/crd.0000000000000440 · Cited by 103 · see citing works
“Necroptosis is a regulated form of cell death with hybrid features of oncosis and apoptosis, which occurs in response to activation of plasmalemmal tumor necrosis factor (TNF) receptors or Toll-like receptors (TLR), and which involves specific receptor-interacting serine/threonineprotein kinases (RIPK1 and RIPK3), the…”
BackgroundRegulation of programmed cell death by Brd4
Hu, J., Pan, D., Guo, L., Chen, K., & Hu, X. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05505-1 · Cited by 95 · see citing works
Zhao, H., Chen, H., Guo, Z., Zhang, W., Yu, H., Zhuang, Z., Zhong, H., & Liu, Z. (2019) · Chemical Engineering Journal · doi:10.1016/j.cej.2020.124314 · Cited by 92 · see citing works
Bloemberg, D., & Quadrilatero, J. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00261.2018 · Cited by 93 · see citing works
“1) In the absence of stress, autophagy operates at a basal level, thereby providing important cellular functions, while apoptotic signaling is kept to a minimum; 2) relatively lowlevel stress induces autophagy as well as activates some antiapoptotic mechanisms to resist or remove stress sources; 3) if deemed unsurviva…”
BackgroundMitochondrial ROS prime the hyperglycemic shift from apoptosis to necroptosis
Deragon, M. A., McCaig, W. D., Patel, P., Haluska, R. J., Hodges, A. L., Sosunov, S. A., Murphy, M. P., Ten, V. S., & LaRocca, T. J. (2020) · Cell Death Discovery · doi:10.1038/s41420-020-00370-3 · Cited by 91 · see citing works
Lu, L., Tian, J., Luo, X., & Peng, J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03587-8 · Cited by 88 · see citing works
The possible roles of necroptosis during cerebral ischemia and ischemia / reperfusion injury
Liao, S., Apaijai, N., Chattipakorn, N., & Chattipakorn, S. C. (2020) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2020.108629 · Cited by 88 · see citing works
Biological events and molecular signaling following MLKL activation during necroptosis
Gong, Y., Guy, C. S., Crawford, J. C., & Green, D. R. (2017) · Cell Cycle · doi:10.1080/15384101.2017.1371889 · Cited by 88 · see citing works
“Dox-inducible hMLKL((1-140))-2Fv-Venus in mlkl¡/¡ MEF, stably expressed with hCHMP4B-mCherry, were treated with 2 mg/mL Dox overnight, followed by 25 nM B/B for 15 min.”
MethodThal, D. R., & Tomé, S. O. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.10.006 · Cited by 85 · see citing works
Lin, F., Jingyuan, X., Liang, F., Huijun, D., Liu, Y., Ren, J., Lin, J., & Linghui, P. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02467-w · Cited by 85 · see citing works
“Pyroptosis refers to programmed cell death that accompanies the release of inflammatory factors [9].”
Wang, N., & Liu, D. (2021) · OncoTargets and Therapy · doi:10.2147/ott.s342613 · Cited by 85 · see citing works
“Moreover, TNF signaling pathway was also found to be involved in balancing cell survival and necroptosis.(28) Univariate Cox analysis suggested that EZH2, PGAM5, TLR4, and TRAF2 were associated with the prognosis of STAD patients.”
BackgroundNecroptosis in cardiovascular disease - a new therapeutic target
Gupta, K., Phan, N., Wang, Q., & Liu, B. (2018) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2018.03.003 · Cited by 84 · see citing works
“Grootjans S, Vanden Berghe T, Vandenabeele P. Initiation and execution mechanisms of necroptosis: an overview.”
MethodInfluentialTRIM24-RIP3 axis perturbation accelerates osteoarthritis pathogenesis
Jeon, J., Noh, H.-J., Lee, H., Park, H.-H., Ha, Y.-J., Park, S., Lee, H., Kim, S., Kang, H., Eyun, S.-I., et al. (2020) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2020-217904 · Cited by 77 · see citing works
Fan, X., Lin, L., Cui, B., Zhao, T., Mao, L., Song, Y., Wang, X., Feng, H., Yu, Q., Zhang, J., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104945 · Cited by 82 · see citing works
Salvadores, N., Moreno‐González, I., Gamez, N., Quiroz, G., Vegas‐Gomez, L., Escandón, M., Jiménez, S., Vitórica, J., Gutiérrez, A., Soto, C. A., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01332-9 · Cited by 81 · see citing works
“The physical interaction between RIPK1, RIPK3, and MLKL within the necrosome complex leads to MLKL phosphorylation, resulting in its oligomerization and execution of necroptosis [33].”
BackgroundNecroptosis in Intestinal Inflammation and Cancer: New Concepts and Therapeutic Perspectives
Negroni, A., Colantoni, E., Cucchiara, S., & Stronati, L. (2020) · Biomolecules · doi:10.3390/biom10101431 · Cited by 80 · see citing works
“Interestingly, other RHIM-containing proteins, such as Toll/interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-ß (TRIF) and the DNA-dependent activator of interferon-regulatory factor (DAI, also known as ZBP1), may interact and activate RIPK3, regardless of RIPK1, leading to necroptosis [35].”
BackgroundThe Autophagy-Initiating Kinase ULK1 Controls RIPK1-Mediated Cell Death
Wu, W., Wang, X., Berleth, N., Deitersen, J., Hieke, N., Böhler, P., Schlütermann, D., Stuhldreier, F., Cox, J., Schmitz, K., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107547 · Cited by 76 · see citing works
Molecular mechanisms and functions of pyroptosis in sepsis and sepsis-associated organ dysfunction
Wen, R., Liu, Y., Tong, X.-X., Zhang, T., & Yang, N. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.962139 · Cited by 80 · see citing works
“, 2017) Necroptosis (Pasparakis and Vandenabeele, 2015; Grootjans et al., 2017) NETosis (Li et al.”
CHIP as a therapeutic target for neurological diseases
Zhang, S., Hu, Z., Mao, C., Shi, C., & Xu, Y. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02953-5 · Cited by 72 · see citing works
The renaissance of anti‐neoplastic immunity from tumor cell demise
Ma, Y., Pitt, J. M., Li, Q., & Yang, H. (2017) · Immunological Reviews · doi:10.1111/imr.12586 · Cited by 74 · see citing works
Die Another Day: Inhibition of Cell Death Pathways by Cytomegalovirus
Brune, W., & Andoniou, C. E. (2017) · Viruses · doi:10.3390/v9090249 · Cited by 73 · see citing works
“Receptor interacting protein kinase-1 and -3 (RIPK1 and RIPK3) are key mediators of necroptosis with the study of signalling events downstream of TNFR1 being critical in understanding how these kinases promote necrotic death [29].”
BackgroundZhou, M., He, J., Shi, Y., Liu, X., Luo, S., Cheng, C., Ge, W., Qu, C.-Y., Du, P., & Chen, Y. (2020) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjaa131 · Cited by 73 · see citing works
Regulated necrosis, a proinflammatory cell death, potentially counteracts pathogenic infections
Zhang, G., Wang, J., Zhao, Z., Xin, T., Fan, X., Shen, Q., Raheem, A., Lee, C. R., Jiang, H., & Ding, J. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05066-3 · Cited by 74 · see citing works
“Under certain circumstances, as the inhibition of caspase, TLR3 or TLR4 stimulation induce necroptosis with the contribution of TRIF and RIP3 [10, 40, 70].”
BackgroundKhan, M. B., Lin, J., Wang, B., Chen, C., Huang, Z., Tian, Y., Yuan, Y., & Bu, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.968165 · Cited by 72 · see citing works
Sendtner, N., Seitz, R., Brandl, N., Müller, M., & Gülow, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262010240 · Cited by 75 · see citing works
“TNF is a principal trigger of necroptosis via TNFR1, driving RIPK1–RIPK3 necrosome formation and MLKL activation when apoptotic/survival checkpoints (e.g., caspase-8 or cIAPs) are inhibited [18,163,171,172].”
InfluentialShe, L., Tu, H., Zhang, Y.-Z., Tang, L.-J., Li, N., Ma, Q.-L., Liu, B., Li, Q., Luo, X., & Peng, J. (2019) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-018-06848-8 · Cited by 72 · see citing works
Xu, Y., Gao, H., Hu, Y., Fang, Y., Qi, C., Huang, J., Cai, X., Wu, H., Ding, X., & Zhang, Z. (2019) · Experimental Cell Research · doi:10.1016/j.yexcr.2019.06.008 · Cited by 71 · see citing works
The necroptosis cell death pathway drives neurodegeneration in Alzheimer’s disease
Balusu, S., & Strooper, B. D. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02747-5 · Cited by 73 · see citing works
“Furthermore, the C-terminal death domain (DD) of RIPK1 also mediates both homo and heterodimerization with other intracellular death domain-containing proteins like Fas-associated protein with a death domain (FADD), TNFR1, and FAS [58, 166].”
BackgroundRedundant and receptor-specific activities of TRADD, RIPK1 and FADD in death receptor signaling
Füllsack, S., Rosenthal, A., Wajant, H., & Siegmund, D. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1396-5 · Cited by 70 · see citing works
The Multifaceted Roles of Pyroptotic Cell Death Pathways in Cancer
Wang, M., Jiang, S., Zhang, Y., Li, P., & Wang, K. (2019) · Cancers · doi:10.3390/cancers11091313 · Cited by 68 · see citing works
“These events ultimately lead to necrotic plasma membrane permeabilization and cell death associated with loss of cell and organelle integrity [10].”
BackgroundNecroptosis: A Pathogenic Negotiator in Human Diseases
Chaouhan, H. S., Vinod, C., Mahapatra, N., Yu, S., Wang, I., Chen, K., Yu, T., & Li, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112714 · Cited by 68 · see citing works
“Numerous studies have described that the inhibition of RIPK1 in TLR3/4 receptor-mediated necroptosis does not impair this process [45,46].”
BackgroundPseudomonas aeruginosa Cytotoxins: Mechanisms of Cytotoxicity and Impact on Inflammatory Responses
Wood, S. J., Goldufsky, J. W., Seu, M. Y., Dorafshar, A. H., & Shafikhani, S. H. (2023) · Cells · doi:10.3390/cells12010195 · Cited by 70 · see citing works
“, oncosis)” which is unregulated, instantaneous accidental cell death as the direct result of massive cellular and/or membrane damage caused by extreme physicochemical conditions, and “necroptosis” a form of regulated, protein-based cell death occurring in response to signaling cues and milder physicochemical conditio…”
BackgroundThe potential role of necroptosis in clinical diseases (Review)
Dai, W., Cheng, J. Q., Leng, X., Hu, X., & Ao, Y. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.4922 · Cited by 68 · see citing works
Chen, F., Yang, J., Fang, M., Wu, Y., Su, D., & Sheng, Y. (2022) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.24302 · Cited by 65 · see citing works
- Authors
- Grootjans, S., Vanden Berghe, T., & Vandenabeele, P.
- Affiliations
- Ghent University (BE)
- Corresponding author
- Vandenabeele, Peter
- Venue
- Cell Death & Differentiation
- Published
- 2017-05-12
- Volume
- 24
- Issue
- 7
- Pages
- 1184-1195
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- PMC
- PMC5520172
- OpenAlex
- W2612992363
- Cited by
- 566
- References
- 152
- Citations by year
- 2026: 45 · 2025: 66 · 2024: 68 · 2023: 78 · 2022: 89 · 2021: 64 · 2020: 54 · 2019: 47 · 2018: 41 · 2017: 14
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- Belgian Federal Science Policy Office (IAP7/32)
- Fonds Wetenschappelijk Onderzoek (G.0875.11, FWO G.0A45.12N, FWO G0E04.16N, G078713N, FWO G0787.13N, FWO G.0C37.14N, G0C3714N, G.0A45.12N, FWO G.0875.11, BOF16/MET_V/007, G0E0416N)
- Universiteit Gent (BOF16/MET_V/007, 01M00709)
- Vlaams Instituut voor Biotechnologie (BOF09/01M00709)
- Vlaamse regering (BOF09/01M00709, BOF16/MET_V/007)
- Fondation contre le Cancer (2012-188)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- necroptosis, regulated cell death, RIPK3, RIPK1, MLKL, RHIM domain, Toll-like receptors, TRIF, ZBP1, DAI, pattern recognition receptors, inflammatory diseases, degenerative diseases, infectious diseases, apoptosis, inflammasome activation
- MeSH terms
- Amyloid, Animals, Humans, Models, Biological, Necrosis, Signal Transduction, Apoptosis, Receptor-Interacting Protein Serine-Threonine Kinases
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