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Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
Open accessAbstract
Caspase-8 has two opposing biological functions--it promotes cell death by triggering the extrinsic pathway of apoptosis, but also has a survival activity, as it is required for embryonic development, T-lymphocyte activation, and resistance to necrosis induced by tumour necrosis factor-α (TNF-α) and related family ligands. Here we show that development of caspase-8-deficient mice is completely rescued by ablation of receptor interacting protein kinase-3 (RIPK3). Adult animals lacking both caspase-8 and RIPK3 display a progressive lymphoaccumulative disease resembling that seen with defects in CD95 or CD95-ligand (also known as FAS and FASLG, respectively), and resist the lethal effects of CD95 ligation in vivo. We have found that caspase-8 prevents RIPK3-dependent necrosis without inducing apoptosis by functioning in a proteolytically active complex with FLICE-like inhibitory protein long (FLIP(L), also known as CFLAR), and this complex is required for the protective function.
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“In addition, the assembly of the necrosome upon TNFR1 stimulation impinges on two conditions: (1) pharmacological or genetic CASP8 inactivation [478, 479], and (2) RIPK1 deubiquitination-dependent phosphorylation (at least in some settings), which can be favored by exogenously provided SMAC mimetics, ensuring the release of RIPK1 from complex I (see above) [334, 335, 480, 481].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [479]
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Cites
Two CD95 (APO‐1/Fas) signaling pathways
Scaffidi, C., Fulda, S., Srinivasan, A., Friesen, C., Li, F., Tomaselli, K. J., Debatin, K., Krammer, P. H., & Peter, M. E. (1998) · The EMBO Journal · doi:10.1093/emboj/17.6.1675 · Cited by 3,000
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 · cited 1×
“Necrosis induced by TNF in the presence of caspase inhibitors is dependent on the kinase activity of Receptor-Interacting Protein Kinase-1 (RIPK1)4,8 and RIPK39–11, although the mechanisms remain obscure.”
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
Identification 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 · cited 1×
“Necrosis induced by TNF in the presence of caspase inhibitors is dependent on the kinase activity of Receptor-Interacting Protein Kinase-1 (RIPK1)4,8 and RIPK39–11, although the mechanisms remain obscure.”
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 1,987 · cited 12×
“Cleaved caspase-8 was observed in whole lysates from these cells upon FLIP knockdown and TNF treatment, indicating that active caspase-8 was present in these cells, but was unable to prevent formation of the RIPK1-RIPK3 complex in the absence of FLIP (fig.”
InfluentialRIP3, 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
Lethal effect of the anti-Fas antibody in mice
Ogasawara, J., Watanabe-Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T., & Nagata, S. (1993) · Nature · doi:10.1038/364806a0 · Cited by 1,881
Varfolomeev, E., Schuchmann, M., Luria, V., Chiannilkulchai, N., Beckmann, J., Mett, I., Rebrikov, D., Brodianski, V. M., Kemper, O., Kollet, O., et al. (1998) · Immunity · doi:10.1016/s1074-7613(00)80609-3 · Cited by 1,332
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
FADD: Essential for Embryo Development and Signaling from Some, But Not All, Inducers of Apoptosis
Yeh, W., de la Pompa, J. L., McCurrach, M. E., Shu, H., Elia, A., Shahinian, A., Ng, M. S. W., Wakeham, A. C., Khoo, W., Mitchell, K., et al. (1998) · Science · doi:10.1126/science.279.5358.1954 · Cited by 890
Flagged first, then by citations
Research works printed but not linked: 4
- Geserick, P. et al. Cellular IAPs inhibit a cryptic CD95-induced cell death by limiting RIP1 kinase recruitment. J. Cell Biol. 187, 1037–1054 (2009) · DOI
- Oberst, A. et al. Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation. J. Biol. Chem. 285, 16632–16642 (2010) · DOI · Paper page
- Salmena, L. et al. Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. Genes Dev. 17, 883–895 (2003) · DOI
- Newton, K., Sun, X. & Dixit, V. M. Kinase RIP3 is dispensable for normal NF-κBs, signaling by the B-cell and T-cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4. Mol. Cell. Biol. 24, 1464–1469 (2004) · DOI
Cited by
Sorted by citations
Items 801–900 of 999
Hojo, T., Skarzynski, D. J., & Okuda, K. (2022) · Journal of Reproduction and Development · doi:10.1262/jrd.2022-097 · Cited by 23
Pérez-Chacón, G., Rı́os, C. D. L., & Zapata, J. M. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.08.005 · Cited by 22
IAP antagonists sensitize murine osteosarcoma cells to killing by TNFα
Shekhar, T. M., Miles, M. A., Gupte, A., Taylor, S., Tascone, B., Walkley, C. R., & Hawkins, C. J. (2016) · Oncotarget · doi:10.18632/oncotarget.8980 · Cited by 22
“Caspase-8 has been shown to suppress necroptosis [67, 68], so presumably in this context Q-VD-OPh indirectly stimulated necroptosis by preventing the proteolysis of one or more pro-necroptotic substrates by caspase-8 [22].”
BackgroundResultPharmacological inhibition of caspase‐8 limits lung tumour outgrowth
Terlizzi, M., Crescenzo, V. G. D., Perillo, G., Galderisi, A., Pinto, A., & Sorrentino, R. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13176 · Cited by 22
“In this context, caspase-8 inhibits the kinase RIP3, which is involved in necrosis and predominates in caspase-8-induced apoptosis (Kaiser et al., 2011; Oberst et al., 2011).”
BackgroundDefining PANoptosis: Biochemical and Mechanistic Evaluation of Innate Immune Cell Death Activation
Tweedell, R. E., Hibler, T., & Kanneganti, T. (2024) · Current Protocols · doi:10.1002/cpz1.1112 · Cited by 21
Regulation of inflammatory processes by caspases
Beltrán‐Visiedo, M., Soler-Agesta, R., Sarosiek, K. A., Green, D. R., & Galluzzi, L. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00869-6 · Cited by 23
Self-citationAyazgök, B., & Küçükkılınç, T. T. (2018) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22233 · Cited by 21
Quinacrine Ameliorates Cisplatin-Induced Renal Toxicity via Modulation of Sirtuin-1 Pathway
El‐Magd, N. F. A., Ebrahim, H. A., El‐Sherbiny, M., & Eisa, N. H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910660 · Cited by 21
“Among caspases, caspase-8 is an important mediator for an inflammatory cell death process known as necroptosis [39,40].”
BackgroundXuan, L., Jinming, G., Guan, Y., Wang, H., Wu, H., & Chang, Y. (2021) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2021.11.014 · Cited by 21
Lai, H.-T., Naumova, N., Marchais, A., Gaspar, N., Geoerger, B., & Brenner, C. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.948097 · Cited by 23
Kandula, N., Kumar, S., Mandlem, V., Siddabathuni, A., Singh, S. K., & Kosuru, R. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/7346699 · Cited by 23
“For instance, lethality in caspase-8 de fi cient mice is entirely reversed by the RIP3 deletion, which otherwise dies in utero at day 10.5 of embryonic development [158, 159].”
InfluentialThe mechanism of programmed death and endoplasmic reticulum stress in pulmonary hypertension
Sun, Y., Liu, S., Chen, C., Yang, S., Pei, G., Lin, M., Wang, T., Long, J., Yan, Q., Yao, J., et al. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01373-6 · Cited by 22
Dominguez, S. T., Montgomery, A. B., Haines, G. K., Bloomfield, C. L., & Cuda, C. M. (2017) · Arthritis Research & Therapy · doi:10.1186/s13075-017-1436-4 · Cited by 21
“limit RIPK signaling for necroptosis and prevent apoptosis [24].”
BackgroundInfluentialProgrammed necrosis and its role in management of breast cancer
Thakur, B., Kumar, Y., & Bhatia, A. (2019) · Pathology - Research and Practice · doi:10.1016/j.prp.2019.152652 · Cited by 21
Use of a glycerin-based gel sheeting in scar management.
Baum, T. M., & Busuito, M. J. (1998) · PubMed · Cited by 21
RIPK3 in necroptosis and cancer
Morgan, M. J., & Kim, Y. (2025) · Molecules and Cells · doi:10.1016/j.mocell.2025.100199 · Cited by 21
Mitoneet mediates TNFα induced necroptosis promoted by fructose and ethanol exposure
Shulga, N., & Pastorino, J. G. (2013) · Journal of Cell Science · doi:10.1242/jcs.140764 · Cited by 20
RetractedCurrent understanding of ferroptosis in the progression and treatment of pancreatic cancer
Dong, S., Li, X., Jiang, W., Chen, Z., & Zhou, W. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02166-6 · Cited by 21
The Antigastric Cancer Effect of Triptolide is Associated With H19/NF-κB/FLIP Axis
Yuan, W., Huang, J., Hou, S., Li, H., Bie, L., Chen, B., Li, G., Zhou, Y., & Chen, X. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.918588 · Cited by 21
“The result of Figure 1B showed that only a 10-ng/ml concentration of TNF-α had remarkably decreased the cell viability of MKN45 cells, which was consistent with the published articles (Oberst et al., 2011; Suda et al., 2016).”
ResultZ-DNA enhances immunotherapy by triggering death of inflammatory cancer-associated fibroblasts
Herbert, A. G., & Balachandran, S. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005704 · Cited by 20
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Han, J., Tweedell, R. E., & Kanneganti, T. (2023) · Journal of Visualized Experiments · doi:10.3791/64308 · Cited by 23
The romantic history of signaling pathway discovery in cell death: an updated review
Wang, L., Liu, X., Li, Q.-Q., Zhu, Y., Ren, H.-L., Song, J., Zeng, J., Mei, J., Tian, H., Rong, D., et al. (2023) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-023-04873-2 · Cited by 22
Doglio, M. G., Verboom, L., Sosoranga, E. R., Frising, U. C., Asaoka, T., Gansemans, Y., Nieuwerburgh, F. V., Loo, G., & Wullaert, A. (2023) · Science Immunology · doi:10.1126/sciimmunol.adf4404 · Cited by 20
“…blood neutrophilia in Otulin FL/FL Casp8 +/ − Ripk3 − / − mice might reflect the start of the progressive lymphadenopathy phenotype that develops in Casp8 − / − Ripk3 − / − mice ( 20 , 21 ), which prevented us from assessing autoinflammation levels in Otulin Mye-KO Casp8 − / − Ripk3 − / − mice.”
BackgroundMethodNanomaterials-induced programmed cell death: Focus on mitochondria
Qiao, S., Kang, Y., Tan, X., Zhou, X., Zhang, C., Lai, S., Liu, J., & Shao, L. (2024) · Toxicology · doi:10.1016/j.tox.2024.153803 · Cited by 20
Microbiota and caspase-1/caspase-8 regulate IL-1β-mediated bone disease
Phillips, F. C., Gurung, P., & Kanneganti, T. (2016) · Gut Microbes · doi:10.1080/19490976.2016.1182289 · Cited by 20
“Caspase8–deficient mice are embryonic lethal and can be rescued by breeding with Ripk3¡/¡ mice.(27) To test whether caspase-8 is a direct protease for IL-1b in Pstpip2 mice, Ripk3¡/¡Casp8¡/¡Pstpip2cmo mice were generated.”
BackgroundPescatore, A., Esposito, E., Dráber, P., Walczak, H., & Ursini, M. V. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.245 · Cited by 20
“necrosis.(30,31) The fact that NEMO-A323P-expressing cells did not die after TNF treatment, but were highly sensitive to necroptotic cell death upon stimulation with TNF in the presence of zVAD, demonstrated that (i) the residual activity of Caspase-8 in NEMO-A323P cells was sufficient to prevent necroptosis following…”
BackgroundHIF1a Inhibitor Rescues Acute-on-Chronic Liver Failure
Xie, F., Dong, J., Zhu, Y., Kefei, W., Liu, X., Chen, D., & Meng, Q. (2019) · Annals of Hepatology · doi:10.1016/j.aohep.2019.03.007 · Cited by 20
“Genetic ablation of caspase-8 resulted in embryonic lethality in mice [35].”
BackgroundGeneral In Vitro Caspase Assay Procedures
Boucher, D., Duclos, C., & Denault, J. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-0357-3_1 · Cited by 21
Caspase-8 is essential for maintaining chromosomal stability and suppressing B-cell lymphomagenesis
Hakem, A., Ghamrasni, S. E., Maire, G., Lemmers, B., Karásková, J., Jurisicova, A., Sanchez, O. H., Squire, J. A., & Hakem, R. (2012) · Blood · doi:10.1182/blood-2011-07-367532 · Cited by 20
Self-citationZhang, Y., & Liu, H. (2013) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2013.14.12.7069 · Cited by 21
“Previous reports suggest that c-FLIPL is involved in the regulation of necroptosis, with siRNA-mediated silencing of c-FLIPL sensitizing cells to TNF-α-induced RIP1/RIP3-dependent necroptosis (Oberst et al., 2011).”
BackgroundGrinshpon, R. D., Shrestha, S., Titus‐McQuillan, J. E., Hamilton, P. T., Swartz, P., & Clark, A. C. (2019) · Biochemical Journal · doi:10.1042/bcj20190625 · Cited by 20
Mitochondria as Regulators of Nonapoptotic Cell Death in Cancer
Malla, S., Neupane, R., Sood, S., Hussein, N. A., Abou-Dahech, M. S., Terrero, D., Ashby, C. R., Babu, R. J., & Tiwari, A. K. (2025) · MedComm · doi:10.1002/mco2.70244 · Cited by 20
Necroptotic cell death consequences and disease relevance
Vince, J. E., Davidson, N., & Tanzer, M. C. (2025) · Nature Immunology · doi:10.1038/s41590-025-02298-1 · Cited by 21
A20 is a regulator of necroptosis
Gurung, P., Man, S. M., & Kanneganti, T. (2015) · Nature Immunology · doi:10.1038/ni.3174 · Cited by 19
SHP-1 and IL-1α conspire to provoke neutrophilic dermatoses
Lukens, J. R., & Kanneganti, T. (2014) · Rare Diseases · doi:10.4161/rdis.27742 · Cited by 18
Caspases and immunity in a deadly grip
Rodrigue‐Gervais, I. G., & Saleh, M. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.09.005 · Cited by 20
Programmed cell death with a necrotic-like phenotype
Morgan, M. J., & Liu, Z.-G. (2013) · BioMolecular Concepts · doi:10.1515/bmc-2012-0056 · Cited by 20
An unexpected turn of fortune: targeting TRAIL-Rs in KRAS-driven cancer
von Karstedt, S., & Walczak, H. (2020) · Cell Death Discovery · doi:10.1038/s41420-020-0249-4 · Cited by 19
RIPK3 Promotes Mefv Expression and Pyrin Inflammasome Activation via Modulation of mTOR Signaling
Sharma, D., Malik, A., Balakrishnan, A., Malireddi, R. K. S., & Kanneganti, T. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000244 · Cited by 19
Fayaz, S. M., Kumar, V. S. S., Davis, C. K., & Rajanikant, G. K. (2016) · Molecular Diversity · doi:10.1007/s11030-016-9663-1 · Cited by 18
Detecting Anastasis In Vivo by CaspaseTracker Biosensor
Tang, H. M., Fung, M. C., & Tang, H. L. (2018) · Journal of Visualized Experiments · doi:10.3791/54107 · Cited by 20
Cellular FLICE-Inhibitory Protein Regulates Tissue Homeostasis
Nakano, H., Piao, X., Shindo, R., & Komazawa‐Sakon, S. (2015) · Current topics in microbiology and immunology · doi:10.1007/82_2015_448 · Cited by 19
Oxidation of caspase-8 by hypothiocyanous acid enables TNF-mediated necroptosis
Bozonet, S. M., Magon, N. J., Schwartfeger, A. J., Königstorfer, A., Heath, S. G., Vissers, M. C. M., Morris, V. K., Göbl, C., Murphy, J. M., Salvesen, G. S., et al. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104792 · Cited by 18
“Caspase-8 knockout mice die during embryonic development from excessive necroptosis (9, 33), and human caspase-8 mutations are associated with immunodeficiency and inflammatory bowel disease (34, 35).”
BackgroundSelf-citationYang, J., Geng, Y., Zhao, B., Liu, T., Luo, J.-L., & Gao, X. (2024) · Food & Function · doi:10.1039/d4fo03012e · Cited by 19
Yang, L. M., Wen, Y., Yuan, Z., Zhao, D., Weng, P., Li, Y., Chen, Q., Zhang, W., Hu, H., & Yu, C. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07441-2 · Cited by 18
“Caspase 8, dependent on FADD activation, inhibits necroptosis by shearing RIPK1/RIPK3 [15].”
The Pathogenesis of Necroptosis-Dependent Signaling Pathway in Cerebral Ischemic Disease
Xu, Y., Zhang, J., Ma, L., Zhao, S., Li, S., Huang, T., & Chu, Z. (2018) · Behavioural Neurology · doi:10.1155/2018/6814393 · Cited by 18
Keeping Cell Death in Check: Ubiquitylation-Dependent Control of TNFR1 and TLR Signaling
Griewahn, L., Köser, A., & Maurer, U. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00117 · Cited by 18
Gupta, K., & Liu, B. (2021) · iScience · doi:10.1016/j.isci.2021.102320 · Cited by 17
Wu, M., Huang, Z., Zeng, L., Wang, C., & Wang, D. (2022) · Cardiology Research and Practice · doi:10.1155/2022/6558060 · Cited by 19
“However, this was not the case, and the study found that necroptosis was activated after caspase 8 [117] and FADD [118] were inhibited, which is the first time that the possibility of functional intertwining of different programmed cell deaths was identified [119, 120].”
BackgroundUbiquitin-Mediated Regulation of Cell Death, Inflammation, and Defense of Homeostasis
Meier, P., Morris, O., & Broemer, M. (2015) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2015.07.015 · Cited by 18
“…al., 2014; Declercq et al., 2009; Dondelinger et al., 2013; Duprez et al., 2011; Ermolaeva et al., 2008; Green et al., 2011; O'Donnell et al., 2011; Oberst et al., 2011; Pasparakis & Vandenabeele, 2015; Polykratis et al., 2014; Vandenabeele, Galluzzi, Vanden Berghe, & Kroemer, 2010; Welz et al.,…”
BackgroundInfluentialMaduramicin induces apoptosis and necrosis, and blocks autophagic flux in myocardial H9c2 cells
Chen, X., Chen, L., Jiang, S., & Huang, S. (2017) · Journal of Applied Toxicology · doi:10.1002/jat.3546 · Cited by 18
“Necroptosis is activated by receptor‐interacting protein kinases 1/3 (RIP1/3), and inhibited by caspases, particularly caspase 8 that can proteolytically cleave and inactivate RIP1 and RIP3 (Oberst et al., 2011; Sun & Wang, 2014).”
BackgroundAriana, A., Alturki, N. A., Hajjar, S., Stumpo, D. J., Tiedje, C., Alnemri, E. S., Gaestel, M., Blackshear, P. J., & Sad, S. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011633 · Cited by 17
Protein Kinase-Mediated Decision Between the Life and Death
Engin, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-49844-3_1 · Cited by 20
Effect of necrostatin-1 on sciatic nerve crush injury in rat models
Chen, Y., Wang, X., & Qin, J. (2023) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-023-03565-3 · Cited by 19
Autophagy critically controls skin inflammation and apoptosis-induced stem cell activation
Hove, L. V., Toniolo, A., Ghiasloo, M., Lecomte, K., Boone, F., Ciers, M., Raaijmakers, K., Vandamme, N., Roels, J., Maschalidi, S., et al. (2023) · Autophagy · doi:10.1080/15548627.2023.2247742 · Cited by 18
“…keratinocytes to apoptotic death promoted the precocious activation of HFSCs observed in Δ Ker atg16l1 skin, we crossed the Δ Ker atg16l1 mice onto a CASP8 RIPK3-deficient ( casp8 -/- ripk3 -/- ) genetic background in order to avoid embryonic lethality due to Casp8 deficiency [35,36].”
Divergent roles of RIPK3 and MLKL in high-fat diet–induced obesity and MAFLD in mice
Tye, H., Conos, S. A., Djajawi, T. M., Gottschalk, T. A., Abdoulkader, N., Kong, I. Y., Kammoun, H. L., Narayana, V. K., Kratina, T., Speir, M., et al. (2024) · Life Science Alliance · doi:10.26508/lsa.202302446 · Cited by 17
Poor antibody validation is a challenge in biomedical research: a case study for detection of c-FLIP
Bucur, O., Pennarun, B., Stancu, A. L., Nadler, M. J. S., Muraru, M. S., Bertomeu, T., & Khosravi‐Far, R. (2013) · APOPTOSIS · doi:10.1007/s10495-013-0880-0 · Cited by 17
“Novel c-FLIP functions have also been described whereby c-FLIP forms a proteolytically active complex with caspase 8 critical to inhibit RIPK3dependent necrosis [18, 19].”
BackgroundSchock, S., Young, J. A., He, T. H., Sun, Y., & Winoto, A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0124391 · Cited by 17
Hüttmann, J., Krause, E., Schommartz, T., & Brune, W. (2015) · Journal of Virology · doi:10.1128/jvi.02729-15 · Cited by 17
“M45 inhibits necroptosis by interacting with RIP1 and RIP3 via a RIP homotypic interaction motif (RHIM), thereby inhibiting formation of the necroptosis-inducing RIP1-RIP3 complex (28, 29).”
BackgroundInfluentialGonzaga, A. C. R., Campolina-Silva, G. H., Gomes, H. W., Moura-Cordeiro, J. D., Santos, L. C. F., Mahecha, G. A. B., Santos, M. M., & Oliveira, C. A. (2017) · The Prostate · doi:10.1002/pros.23349 · Cited by 17
Biswas, S., & Shisler, J. L. (2017) · Journal of Virology · doi:10.1128/jvi.00276-17 · Cited by 20
Koraka, P., Martina, B. E. E., van den Ham, H., Zaaraoui‐Boutahar, F., van IJcken, W. F. J., Roose, J. M., van Amerongen, G., Andeweg, A. C., & Osterhaus, A. D. M. E. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00397 · Cited by 17
“For example, CASP-8—a main effector molecule of apoptosis—can also play a key role in suppressing necroptosis (Oberst et al., 2011).”
BackgroundThe Necrosome in Acute Kidney Injury
Xu, Y., & Han, J. (2016) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2016.03.007 · Cited by 17
Gehrke, N., Nagel, M., Straub, B. K., Wörns, M., Schuchmann, M., Galle, P. R., & Schattenberg, J. M. (2017) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00097.2017 · Cited by 17
Distinguishing Necroptosis from Apoptosis
Shlomovitz, I., Zargarian, S., Erlich, Z., Edry‐Botzer, L., & Gerlic, M. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8754-2_4 · Cited by 17
Dasari, T. K., Geiger, R., Karki, R., Banoth, B., Sharma, B. R., Gurung, P., Burton, A. R., & Kanneganti, T. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.010623 · Cited by 17
Sakamaki, K., Iwabe, N., Iwata, H., Imai, K., Takagi, C., Chiba, K., Shukunami, C., Tomii, K., & Ueno, N. (2015) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2015.08.005 · Cited by 16
Lomphithak, T., Choksi, S., Mutirangura, A., Tohtong, R., Tencomnao, T., Usubuchi, H., Unno, M., Sasano, H., & Jitkaew, S. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00661-3 · Cited by 16
“caspase inhibition has previously been reported to cause a switch from apoptosis to necroptosis [62].”
BackgroundZhao, J., Huang, X., McLeod, P., Jiang, J., Liu, W., Haig, A. R., Jevnikar, A. M., Jiang, Z., & Zhang, Z. (2021) · American Journal of Transplantation · doi:10.1111/ajt.16584 · Cited by 16
Programmed Cell Death-Dependent Host Defense in Ocular Herpes Simplex Virus Infection
Guo, H., Koehler, H. S., Dix, R. D., & Mocarski, E. S. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.869064 · Cited by 20
“…delicate balance of apoptosis and necroptosis pathways was first brought to light in studies that revealed a RIPK1–RIPK3-dependent process dictating midgestational embryonic lethality of caspase-8-deficient mice (Kaiser et al., 2011; Oberst et al., 2011) or FADD-deficient mice (Zhang et al., 2011).”
BackgroundPathway of Cell Death and Its Role in Virus Infection
Chen, X., Zhang, W., Yi, W., Liu, Y., Bi, X., Lin, Y., Deng, W., Dong, J., Li, M., & Xie, Y. (2022) · Viral Immunology · doi:10.1089/vim.2022.0010 · Cited by 16
Caspase cleavage of RIPK3 after Asp333 is dispensable for mouse embryogenesis
Newton, K., Wickliffe, K. E., Maltzman, A., Dugger, D. L., Webster, J. D., Guo, H., & Dixit, V. M. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-023-01255-5 · Cited by 17
“The catalytic activity of caspase-8 mediates both apoptosis induction and necroptosis suppression [9, 14, 15].”
InfluentialThe contribution of the programmed cell death machinery in innate immune cells to lupus nephritis
Tsai, F., Perlman, H., & Cuda, C. M. (2016) · Clinical Immunology · doi:10.1016/j.clim.2016.10.007 · Cited by 16
Caspase-8 and FLIP Regulate RIG-I/MDA5-induced Innate Immune Host Responses to Picornaviruses
Buskiewicz, I. A., Koenig, A., Huber, S. A., & Budd, R. C. (2012) · Future Virology · doi:10.2217/fvl.12.115 · Cited by 16
Techniques to Distinguish Apoptosis from NecroptosisPreprint
Feoktistova, M., Wållberg, F., Tenev, T., Geserick, P., Leverkus, M., & Meier, P. (2016) · Cold Spring Harbor Protocols · doi:10.1101/pdb.top070375 · Cited by 16
“For example, ectopic expression of the short or long isoform of cFLIP blocks apoptosis induced by treatment with TNF and IAP-antagonists (Feoktistova et al. 2011; Oberst et al. 2011; Pop et al. 2011) (Fig.”
Ge, Q., Zhang, T., Yu, J., Lu, X., Xiao, S., Zhang, T., Qing, T., Xiao, Z., Zeng, L., & Luo, L. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117706 · Cited by 16
Kobayashi, Y., Hashizume, H., Takiguchi, S., Ji, J., Kawano, R., Koiwai, K., Yamamoto, H., Elbadawy, M., Omatsu, T., Abugomaa, A., et al. (2025) · Scientific Reports · doi:10.1038/s41598-024-84297-0 · Cited by 20
Bhatti, I. A., Abhari, B. A., & Fulda, S. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.07.008 · Cited by 18
Liao, S., Luo, Y., Chunchai, T., Singhanat, K., Arunsak, B., Benjanuwattra, J., Apaijai, N., Chattipakorn, N., & Chattipakorn, S. C. (2022) · Inflammation Research · doi:10.1007/s00011-022-01590-2 · Cited by 14
Mechanisms of Cell Death and Relevance to Drug Toxicity
Dara, L., Han, D., & Kaplowitz, N. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-387817-5.00006-6 · Cited by 15
Modulation of Cell Death Pathways by Hepatitis C Virus Proteins in Huh7.5 Hepatoma Cells
Masalova, O. V., Ивановна, Л. Е., Solyev, P. N., Zakirova, N. F., Prassolov, V., Kochetkov, S. N., Ivanov, A. V., & Aa, K. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112346 · Cited by 15
“Interestingly, in HCV-unrelated studies, caspase-8 was shown to inhibit necrosis [55].”
BackgroundRole of Caspases and Gasdermin A during HSV-1 Infection in Mice
Li, L., Kovacs, S. B., Jørgensen, I., Larson, H. N., Lazear, H. M., & Miao, E. A. (2022) · Viruses · doi:10.3390/v14092034 · Cited by 15
“Since Casp8–/– mice are embryonically lethal due to unchecked necroptosis that is executed by the RIPK3-MLKL axis [33,79], we compared WT and Casp8+/–Ripk3–/– with Casp8–/–Ripk3–/– mice during HSV-1 skin infection to assess the role of caspase-8.”
BackgroundLadik, M., Valenta, H., Erard, M., Vandenabeele, P., & Riquet, F. B. (2023) · Frontiers in Cell Death · doi:10.3389/fceld.2023.1127330 · Cited by 14
“This regulated cell death modality which appears to play an essential role during development (Kaiser et al., 2011; Oberst et al., 2011), is also associated with pathological situations such as inflammatory diseases (e.”
BackgroundMalireddi, R. K. S., Bynigeri, R. R., Mall, R., Connelly, J. P., Pruett‐Miller, S. M., & Kanneganti, T. (2023) · Communications Biology · doi:10.1038/s42003-023-05414-9 · Cited by 16
Modulation of extrinsic apoptotic pathway by intracellular glycosylation
Seyrek, K., Ivanisenko, N. V., König, C., & Lavrik, I. N. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2024.01.003 · Cited by 17
Regulated Cell Death Pathways in Pathological Cardiac Hypertrophy
Wu, S., Ding, D., & Wang, D. (2024) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2510366 · Cited by 14
Mechanistic Insights into Influenza A Virus-Induced Cell Death and Emerging Treatment Strategies
Sun, Y., & Liu, K. (2024) · Veterinary Sciences · doi:10.3390/vetsci11110555 · Cited by 20
Proteolytic control of regulated necrosis
Chico, J. F., Saggau, C., & Adam, D. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2017.05.025 · Cited by 16
Zhong, M.-Y., Huang, Y., Zeng, B., Xu, L., Zhong, C.-S., Qiu, J.-H., Ye, X.-J., Chen, M., Hu, B., Ouyang, D., et al. (2021) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2021004 · Cited by 14
Endothelial Caspase-8 prevents fatal necroptotic hemorrhage caused by commensal bacteria
Bader, S. M., Preston, S., Saliba, K., Lipszyc, A. C., Grant, Z. L., Mackiewicz, L., Baldi, A., Hempel, A., Clark, M. P., Peiris, T., et al. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-01042-8 · Cited by 14
“These data align with the notion that Caspase-8 activity triggers apoptosis [10], whereas its absence licenses MLKL-dependent necroptotic cell death [22, 23, 30].”
BackgroundNon-coding RNAs in necroptosis, pyroptosis, and ferroptosis in cardiovascular diseases
Cai, Y., Zhou, Y., Li, Z., Xia, P., ChenFu, X., Shi, A., Zhang, J., & Yu, P. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.909716 · Cited by 14
Dual Face Apoptotic Machinery: From Initiator of Apoptosis to Guardian of Necroptosis
Declercq, W., Takahashi, N., & Vandenabeele, P. (2011) · Immunity · doi:10.1016/j.immuni.2011.10.007 · Cited by 14
“The importance of controlling necroptosis during development is evident from the embryonic mortality of Fadd / or Casp8 / mice, which can be rescued by ablation of RIPK1 or RIPK3 (Kaiser et al., 2011; Oberst et al., 2011; Zhang et al., 2011).”
BackgroundSipieter, F., Ladik, M., Vandenabeele, P., & Riquet, F. B. (2014) · Biotechnology Journal · doi:10.1002/biot.201300200 · Cited by 14
DONG, Y., BAO, C., Yu, J., & Liu, X. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.5311 · Cited by 14
“Previous studies have demonstrated that knockout of RIP3 is able to promote cell survival even in the lethal phenotype of caspase‑8 deficient mice (12,38).”
Fuke, N., Takagi, T., Higashimura, Y., Tsuji, T., Umeda, R., Mizushima, K., Tanaka, M., Suganuma, H., Aizawa, K., Yajima, N., et al. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izx003 · Cited by 15
Peterson, L. W., & Brodsky, I. E. (2020) · Current Opinion in Microbiology · doi:10.1016/j.mib.2020.01.015 · Cited by 12
Amstein, L., Ackermann, J., Hannig, J., Đikić, I., Fulda, S., & Koch, I. (2022) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1010383 · Cited by 14
“While cFLIPL, binding to CASP8 and FADD, has a survival function, blocking apoptosis and necroptosis, cFLIPS, binding to CASP8, inhibits full activation of caspase activity [89,90].”
BackgroundSelective induction of programmed cell death using synthetic biology tools
Shkarina, K., & Brož, P. (2023) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2023.07.012 · Cited by 16
“In viable cells, caspase-8 activity is essential for putting a brake on nec-roptosis [84], and both its enzymatic and non-enzymatic activity contributes to the regulation of NF-kB signaling and gene expression independently of apoptosis [85,86].”
BackgroundExploring caspase functions in mouse models
Švandová, E., Veselá, B., Janečková, E., Chai, Y., & Matalová, E. (2024) · APOPTOSIS · doi:10.1007/s10495-024-01976-z · Cited by 14
“Apart from the apoptosis, caspase-8 is essential for inhibition of necroptosis mediated by Receptor Inter - acting Serine/Threonine Kinase (RIPK3) and Mixed Lin - eage Kinase domain-Like (MLKL) [79 – 82 ].”
BackgroundThe interaction between RIPK1 and FADD controls perinatal lethality and inflammation
Rodríguez, D. A., Tummers, B., Shaw, J. J. P., Quarato, G., Weinlich, R., Cripps, J. G., Fitzgerald, P., Janke, L. J., Pelletier, S. W., Crawford, J. C., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114335 · Cited by 14
“Since the embryonic lethality of Fadd −/− or Casp8 −/− mice can be prevented by co-ablating Ripk3 or Mlkl 2–4, 12 and the RIPK1 To determine if the lethal effects of RIPK3 in our mutant mice were exclusively due to necroptosis, we ablated the necroptosis effector MLKL. Ripk1 RE/RE Mlkl −/− mice…”
BackgroundSelf-citation
Metadata
- Authors
- Oberst, A., Dillon, C. P., Weinlich, R., McCormick, L. L., Fitzgerald, P., Pop, C., Hakem, R., Salvesen, G. S., & Green, D. R.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Green, Douglas R.
- ORCID
- Venue
- Nature
- Published
- 2011-03-02
- Volume
- 471
- Issue
- 7338
- Pages
- 363-367
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3077893
- OpenAlex
- W1975593978
- Cited by
- 1,278
- References
- 32
- Citations by year
- 2026: 49 · 2025: 68 · 2024: 84 · 2023: 69 · 2022: 88 · 2021: 81 · 2020: 88 · 2019: 71 · 2018: 87 · 2017: 80 · 2016: 102 · 2015: 83 · 2014: 116 · 2013: 81 · 2012: 81
- FWCI
- 42.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Ariad Pharmaceuticals
- National Institutes of Health
- Canadian Institutes of Health Research
- National Cancer Institute (P01CA069381)
- National Institute of Allergy and Infectious Diseases (R01AI044828, R37AI044828)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- caspase-8, RIPK3, necroptosis, apoptosis, death receptors, Fas, embryonic lethality, Fas ligand, TNF-alpha resistance, cell death regulation, proteolytic complex, lymphocyte activation
- MeSH terms
- Animals, Cell Line, Female, Male, Necrosis, Phenotype, Tumor Necrosis Factor-alpha, Viral Proteins, Serpins, Apoptosis, fas Receptor, Multiprotein Complexes, Mice, Caspase 8, Receptor-Interacting Protein Serine-Threonine Kinases, CASP8 and FADD-Like Apoptosis Regulating Protein, Biocatalysis, Caspase Inhibitors
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