Protective Roles for Caspase-8 and cFLIP in Adult Homeostasis

Weinlich, Ricardo; Oberst, Andrew; Dillon, Christopher P.; Janke, Laura J.; Milasta, Sandra; Lukens, John R.; Rodriguez, Diego A.; Gurung, Prajwal; Savage, Chandra; Kanneganti, Thirumala D.; Green, Douglas R.

doi:10.1016/j.celrep.2013.08.045

Cited by 157Cell death mechanisms and regulationNF-κB Signaling PathwaysInflammasome and immune disorders

Protective Roles for Caspase-8 and cFLIP in Adult Homeostasis

Open access

Weinlich, Ricardo, Oberst, Andrew, Dillon, Christopher P., Janke, Laura J., Milasta, Sandra, Lukens, John R., Rodriguez, Diego A., Gurung, Prajwal +3 more·2013·Cell Reports

DOI 10.1016/j.celrep.2013.08.045PMC PMC3843376

Open this paper in CoChat — free account

Abstract

Caspase-8 or cellular FLICE-like inhibitor protein (cFLIP) deficiency leads to embryonic lethality in mice due to defects in endothelial tissues. Caspase-8(-/-) and receptor-interacting protein kinase-3 (RIPK3)(-/-), but not cFLIP(-/-) and RIPK3(-/-), double-knockout animals develop normally, indicating that caspase-8 antagonizes the lethal effects of RIPK3 during development. Here, we show that the acute deletion of caspase-8 in the gut of adult mice induces enterocyte death, disruption of tissue homeostasis, and inflammation, resulting in sepsis and mortality. Likewise, acute deletion of caspase-8 in a focal region of the skin induces local keratinocyte death, tissue disruption, and inflammation. Strikingly, RIPK3 ablation rescues both phenotypes. However, acute loss of cFLIP in the skin produces a similar phenotype that is not rescued by RIPK3 ablation. TNF neutralization protects from either acute loss of caspase-8 or cFLIP. These results demonstrate that caspase-8-mediated suppression of RIPK3-induced death is required not only during development but also for adult homeostasis. Furthermore, RIPK3-dependent inflammation is dispensable for the skin phenotype.

Integrity signals

Registry

Crossref · 10.1016/j.celrep.2013.08.045

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Concurrent deletion of Ripk3 averts perturbations of cutaneous and intestinal homeostasis imposed by tissue-specific ablation of Fadd or Casp8.
“Along similar lines, the concurrent deletion of Ripk3 averts perturbations of cutaneous and intestinal homeostasis imposed by the tissue-specific ablation of Fadd or Casp8 [483, 487, 488].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [483]
Cflar−/− mice require concomitant knockout of Ripk3 and Fadd to develop into adulthood, underscoring inhibitory role of c-FLIP in both necroptosis and extrinsic apoptosis.
“Of note, Cflar−/− mice require the concomitant knockout of Ripk3 and Fadd to develop into adulthood, which underscores the inhibitory role of c-FLIP in both necroptosis and extrinsic apoptosis reported above [483, 486].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [483]

Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
Srinivas, S., Watanabe, T., Lin, C.-S., William, C. M., Tanabe, Y., Jessell, T. M., & Costantini, F. (2001) · BMC Developmental Biology · doi:10.1186/1471-213x-1-4 · Cited by 3,121 · see citing works
Inhibition of death receptor signals by cellular FLIP
Irmler, M., Thome, M., Hahne, M., Schneider, P., Hofmann, K., Steiner, V., Bodmer, J.-L., Schröter, M., Burns, K., Mattmann, C., et al. (1997) · Nature · doi:10.1038/40657 · Cited by 2,548 · 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
Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally.
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 · see citing works
Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
Oberst, A., Dillon, C. P., Weinlich, R., McCormick, L. L., Fitzgerald, P., Pop, C., Hakem, R., Salvesen, G. S., & Green, D. R. (2011) · Nature · doi:10.1038/nature09852 · Cited by 1,278 · cited 8× · see citing works
“Embryonic lethality in caspase-8−/− mice can be fully rescued by ablation of RIPK3 (Kaiser et al., 2011; Oberst et al., 2011); therefore four genotypes were examined: CreER−, casp8f/f, ripk3+/+; CreER−, casp8f/f, ripk3−/−; CreER+, casp8f/f, ripk3+/+ and CreER+, casp8f/f, ripk3−/−.”
BackgroundMethodInfluentialSelf-citation
RIP3 mediates the embryonic lethality of caspase-8-deficient mice
Kaiser, W. J., Upton, J. W., Long, A. B., Livingston-Rosanoff, D., Daley-Bauer, L. P., Hakem, R., Caspary, T., & Mocarski, E. S. (2011) · Nature · doi:10.1038/nature09857 · Cited by 1,057 · see citing works
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 886 · see citing works
Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis
Günther, C., Martini, E., Wittkopf, N., Amann, K., Weigmann, B., Neumann, H., Waldner, M. J., Hedrick, S. Μ., Tenzer, S., Neurath, M. F., et al. (2011) · Nature · doi:10.1038/nature10400 · Cited by 882 · see citing works
The protein structures that shape caspase activity, specificity, activation and inhibition
Fuentes‐Prior, P., & Salvesen, G. S. (2004) · Biochemical Journal · doi:10.1042/bj20041142 · Cited by 877 · see citing works
The Specific and Essential Role of MAVS in Antiviral Innate Immune Responses
Sun, Q., Sun, L., Liu, H.-H., Chen, X., Seth, R. B., Forman, J., & Chen, Z. J. (2006) · Immunity · doi:10.1016/j.immuni.2006.04.004 · Cited by 604 · see citing works
FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation
Welz, P.-S., Wullaert, A., Vlantis, K., Kondylis, V., Fernández-Majada, V., Ermolaeva, M., Kirsch, P., Sterner-Kock, A., van Loo, G., & Pasparakis, M. (2011) · Nature · doi:10.1038/nature10273 · Cited by 594 · cited 2× · see citing works
“Although there is no specific marker for necroptosis, the combination of H&E, TUNEL, cleaved caspase-3 staining and ultrastructure is evidence for non-apoptotic, necrosis-like cell death (Bonnet et al., 2011; Gunther et al., 2011; Welz et al., 2011).”
Background
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
Cellular FLICE-inhibitory Protein Splice Variants Inhibit Different Steps of Caspase-8 Activation at the CD95 Death-inducing Signaling Complex
Krueger, A., Schmitz, I., Baumann, S., Krammer, P. H., & Kirchhoff, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101780200 · Cited by 565 · see citing works
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
Newton, 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
Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity.Preprint
Salmena, L., Lemmers, B., Hakem, A., Matysiak-Zablocki, E., Murakami, K., Au, P. Y. B., Berry, D., Tamblyn, L., Shehabeldin, A., Migon, E., et al. (2003) · Genes & Development · doi:10.1101/gad.1063703 · Cited by 517 · see citing works
Requirement for Casper (c-FLIP) in Regulation of Death Receptor–Induced Apoptosis and Embryonic Development
Yeh, W.-C., Itie, A., Elia, A. J., Ng, M., Shu, H.-B., Wakeham, A., Mirtsos, C., Suzuki, N., Bonnard, M., Goeddel, D. V., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)80214-9 · Cited by 515 · see citing works
Inhibitor of Apoptosis Proteins Limit RIP3 Kinase-Dependent Interleukin-1 Activation
Vince, J. E., Wong, W. W.-L., Gentle, I., Lawlor, K. E., Allam, R., O'Reilly, L., Mason, K., Gross, O., Ma, S., Guarda, G., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.012 · Cited by 491 · see citing works
Caspase-8 Serves Both Apoptotic and Nonapoptotic Roles1
Kang, T., Ben-Moshe, T., Varfolomeev, E., Pewzner‐Jung, Y., Yogev, N., Jurewicz, A., Waisman, A., Brenner, O., Haffner, R., Gustafsson, E., et al. (2004) · Journal of Immunology · doi:10.4049/jimmunol.173.5.2976 · Cited by 425 · see citing works
Caspase-8 Blocks Kinase RIPK3-Mediated Activation of the NLRP3 Inflammasome
Kang, T.-B., Yang, S.-H., Toth, B., Kovalenko, A., & Wallach, D. (2013) · Immunity · doi:10.1016/j.immuni.2012.09.015 · Cited by 419 · 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
Survival Function of the FADD-CASPASE-8-cFLIPL Complex
Dillon, C. P., Oberst, A., Weinlich, R., Janke, L. J., Kang, T.-B., Ben-Moshe, T., Mak, T. W., Wallach, D., & Green, D. R. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.03.010 · Cited by 331 · cited 6× · see citing works
“, 2011), and can also sensitize to FADD-caspase-8dependent apoptosis (Dillon et al., 2012; Irmler et al., 1997; Yeh et al., 2000).”
BackgroundResultInfluentialSelf-citation
The Adaptor Protein FADD Protects Epidermal Keratinocytes from Necroptosis In Vivo and Prevents Skin Inflammation
Bonnet, M. C., Preukschat, D., Welz, P.-S., van Loo, G., Ermolaeva, M. A., Bloch, W., Haase, I., & Pasparakis, M. (2011) · Immunity · doi:10.1016/j.immuni.2011.08.014 · Cited by 295 · see citing works
A Noninvasive Genetic/Pharmacologic Strategy for Visualizing Cell Morphology and Clonal Relationships in the Mouse
Badea, T. C., Wang, Y., & Nathans, J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-06-02314.2003 · Cited by 256 · see citing works
Different Subcellular Distribution of Caspase-3 and Caspase-7 following Fas-induced Apoptosis in Mouse Liver
Chandler, J. M., Cohen, G. M., & MacFarlane, M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.18.10815 · Cited by 237 · see citing works
Means to an end: apoptosis and other cell death mechanisms
(2011) · Choice Reviews Online · doi:10.5860/choice.48-5678 · Cited by 224 · see citing works
Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease
Kovalenko, A., Kim, J., Kang, T., Rajput, A., Bogdanov, K., Dittrich‐Breiholz, O., Kracht, M., Brenner, O. J., & Wallach, D. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090616 · Cited by 212 · see citing works
Metabolic inhibitors sensitize for CD95 (APO-1/Fas)-induced apoptosis by down-regulating Fas-associated death domain-like interleukin 1-converting enzyme inhibitory protein expression.
Fulda, S., Meyer, É., & Debatin, K. (2000) · PubMed · Cited by 203 · see citing works
Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease
Takeuchi, O., Fisher, J. K., Suh, H., Harada, H., Malynn, B. A., & Korsmeyer, S. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504783102 · Cited by 203 · see citing works
RIG-I RNA Helicase Activation of IRF3 Transcription Factor Is Negatively Regulated by Caspase-8-Mediated Cleavage of the RIP1 Protein
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
An auxiliary mode of apoptotic DNA fragmentation provided by phagocytesPreprint
McIlroy, D., Tanaka, M., Sakahira, H., Fukuyama, H., Suzuki, M., Yamamura, K., Ohsawa, Y., Uchiyama, Y., & Nagata, S. (2000) · Genes & Development · doi:10.1101/gad.14.5.549 · Cited by 193 · see citing works
Oral IDN‐6556, an antiapoptotic caspase inhibitor, may lower aminotransferase activity in patients with chronic hepatitis C†
Pockros, P. J., Schiff, E. R., Shiffman, M. L., McHutchison, J. G., Gish, R. G., Afdhal, N. H., Makhviladze, M., Huyghe, M., Hecht, D., Oltersdorf, T., et al. (2007) · Hepatology · doi:10.1002/hep.21664 · Cited by 190 · see citing works
Caspase inhibitors: viral, cellular and chemical
Callus, B. A., & Vaux, D. L. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402034 · Cited by 190 · see citing works
Cutting Edge: Innate Immunity Conferred by B Cells Is Regulated by Caspase-8
Beisner, D. R., Ch’en, I. L., Kolla, R. V., Hoffmann, A., & Hedrick, S. Μ. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.6.3469 · Cited by 181 · see citing works
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of GS-9450 in Subjects With Nonalcoholic Steatohepatitis
Ratziu, V., Sheikh, M. Y., Sanyal, A. J., Lim, J. K., Conjeevaram, H. S., Chalasani, N., Abdelmalek, M. F., Bakken, A., Renou, C., Palmer, M., et al. (2011) · Hepatology · doi:10.1002/hep.24747 · Cited by 164 · see citing works
Dynamic expression of epidermal caspase 8 simulates a wound healing response
Lee, P., Lee, D.-J., Chan, C., Chen, S.-W., Ch’en, I., & Jamora, C. (2009) · Nature · doi:10.1038/nature07687 · Cited by 163 · 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
Self-citation
ICE-protease inhibitors block murine liver injury and apoptosis caused by CD95 or by TNF-α
Künstle, G., Leist, M., Uhlig, S., Révész, L., Feifel, R., MacKenzie, A. R., & Wendel, A. (1997) · Immunology Letters · doi:10.1016/s0165-2478(96)02642-9 · Cited by 134 · see citing works
c-FLIP Maintains Tissue Homeostasis by Preventing Apoptosis and Programmed Necrosis
Piao, X., Komazawa‐Sakon, S., Nishina, T., Koike, M., Piao, J., Ehlken, H., Kurihara, H., Hara, M., van Rooijen, N., Schütz, G., et al. (2012) · Science Signaling · doi:10.1126/scisignal.2003558 · Cited by 78 · see citing works
Ripped to death
Weinlich, R., Dillon, C. P., & Green, D. R. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.09.002 · Cited by 68 · see citing works
Self-citation
FLIP: a novel regulator of macrophage differentiation and granulocyte homeostasis
Huang, Q.-Q., Perlman, H., Huang, Z., Birkett, R., Kan, L., Agrawal, H., Misharin, A. V., Gurbuxani, S. K., Crispino, J. D., & Pope, R. M. (2010) · Blood · doi:10.1182/blood-2009-11-252841 · Cited by 31 · see citing works
c-FLIP Maintains Tissue Homeostasis by Preventing Apoptosis and Programmed Necrosis
朴, 雪. (2014) · Institutional Repositories DataBase (IRDB) · Cited by 29 · see citing works
Anti‐inflammatory functions of the “apoptotic” caspases
Wallach, D., Kang, T., Rajput, A., Kim, J., Bogdanov, K., Yang, S., & Kovalenko, A. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05742.x · Cited by 9 · see citing works

Flagged first, then by citations

1 of the 43 references couldn’t be matched to a known paper.

Sorted by citations

Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018.
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-citation
Cell death: a review of the major forms of apoptosis, necrosis and autophagy
D'Arcy, M. (2019) · Cell Biology International · doi:10.1002/cbin.11137 · Cited by 2,324 · 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
Necroptosis in development, inflammation and disease
Weinlich, R., Oberst, A., Beere, H. M., & Green, D. R. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.149 · Cited by 1,016 · see citing works
Self-citation
Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases
Yuan, J., Amin, P., & Ofengeim, D. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0093-1 · Cited by 967 · see citing works
Death by TNF: a road to inflammation
Loo, G., & Bertrand, M. J. M. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00792-3 · Cited by 977 · see citing works
Mechanisms regulating skin immunity and inflammation
Pasparakis, M., Haase, I., & Nestle, F. O. (2014) · Nature reviews. Immunology · doi:10.1038/nri3646 · Cited by 896 · see citing works
Caspase‐8: regulating life and death
Tummers, B., & Green, D. R. (2017) · Immunological Reviews · doi:10.1111/imr.12541 · Cited by 754 · see citing works
Self-citation
Necroptosis: Mechanisms and Relevance to Disease
Galluzzi, L., Kepp, O., Chan, F. K.-M., & Kroemer, G. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-052016-100247 · Cited by 721 · 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
Self-citation
Regulated Cell Death in AKI
Linkermann, A., Chen, G., Dong, G., Kunzendorf, U., Krautwald, S., & Dong, Z. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014030262 · Cited by 564 · see citing works
The diverse role of RIP kinases in necroptosis and inflammation
Silke, J., Rickard, J. A., & Gerlic, M. (2015) · Nature Immunology · doi:10.1038/ni.3206 · Cited by 522 · see citing works
Necroptosis in health and diseases
Zhou, W., & Yuan, J. (2014) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2014.07.013 · Cited by 414 · see citing works
Necroptosis and Inflammation
Newton, K., & Manning, G. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014830 · Cited by 401 · see citing works
Characterization of RIPK3-mediated phosphorylation of the activation loop of MLKL during necroptosis
Rodríguez, D. A., Weinlich, R., Brown, S., Guy, C. S., Fitzgerald, P., Dillon, C. P., Oberst, A., Quarato, G., Low, J. A., Cripps, J. G., et al. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.70 · Cited by 379 · see citing works
Self-citation
RIPK1 and RIPK3: critical regulators of inflammation and cell death
Newton, K. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.01.001 · Cited by 367 · see citing works
Die another way – non-apoptotic mechanisms of cell death
Tait, S. W. G., Ichim, G., & Green, D. R. (2014) · Journal of Cell Science · doi:10.1242/jcs.093575 · Cited by 366 · see citing works
Self-citation
Apoptotic cell death in disease—Current understanding of the NCCD 2023
Vitale, I., Pietrocola, F., Guilbaud, E., Aaronson, S. A., Abrams, J., Adam, D., Agostini, M., Agostinis, P., Alnemri, E. S., Altucci, L., et al. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01153-w · Cited by 359 · see citing works
Self-citation
Onto better TRAILs for cancer treatment
de Miguel, D., Lemke, J., Anel, A., Walczak, H., & Martínez‐Lostao, L. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2015.174 · Cited by 304 · see citing works
A positive feedback loop between RIP3 and JNK controls non‐alcoholic steatohepatitis
Gautheron, J., Vucur, M., Reisinger, F., Cardenas, D. V., Roderburg, C., Koppe, C., Kreggenwinkel, K., Schneider, A. T., Bartneck, M., Neumann, U. P., et al. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201403856 · Cited by 314 · see citing works
Checkpoints in TNF-Induced Cell Death: Implications in Inflammation and Cancer
Annibaldi, A., & Meier, P. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.11.002 · Cited by 287 · see citing works
Dying cells fan the flames of inflammation
Newton, K., Dixit, V. M., & Kayagaki, N. (2021) · Science · doi:10.1126/science.abi5934 · Cited by 278 · see citing works
FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells
Schwarzer, R., Jiao, H., Wachsmuth, L., Tresch, A., & Pasparakis, M. (2020) · Immunity · doi:10.1016/j.immuni.2020.04.002 · Cited by 277 · see citing works
RIP kinases as modulators of inflammation and immunity
He, S., & Wang, X. (2018) · Nature Immunology · doi:10.1038/s41590-018-0188-x · Cited by 246 · see citing works
An Inflammatory Perspective on Necroptosis
Kearney, C. J., & Martin, S. J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.024 · Cited by 227 · see citing works
The interplay of IKK , NF ‐κB and RIPK 1 signaling in the regulation of cell death, tissue homeostasis and inflammation
Kondylis, V., Kumari, S., Vlantis, K., & Pasparakis, M. (2017) · Immunological Reviews · doi:10.1111/imr.12550 · Cited by 226 · see citing works
Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis
Wegner, K. W., Saleh, D., & Degterev, A. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.12.005 · Cited by 188 · see citing works
Holding RIPK1 on the Ubiquitin Leash in TNFR1 Signaling
Peltzer, N., Darding, M., & Walczak, H. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.01.006 · Cited by 184 · see citing works
Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis
Kumari, S., Redouane, Y., López-Mosqueda, J., Shiraishi, R., Romanowska, M., Lutzmayer, S., Kuiper, J. W., Martínez, C., Đikić, I., Pasparakis, M., et al. (2014) · eLife · doi:10.7554/elife.03422 · Cited by 176 · see citing works
Novel Roles for Caspase-8 in IL-1β and Inflammasome Regulation
Gurung, P., & Kanneganti, T. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.08.025 · Cited by 178 · see citing works
Self-citation
FLIP the Switch: Regulation of Apoptosis and Necroptosis by cFLIP
Tsuchiya, Y., Nakabayashi, O., & Nakano, H. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161226232 · Cited by 172 · see citing works
Myeloid-Derived Suppressor Activity Is Mediated by Monocytic Lineages Maintained by Continuous Inhibition of Extrinsic and Intrinsic Death Pathways
Haverkamp, J. M., Smith, A. M., Weinlich, R., Dillon, C. P., Qualls, J. E., Neale, G. A. M., Koss, B. S., Kim, Y., Bronte, V., Herold, M. J., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.10.020 · Cited by 167 · see citing works
Self-citation
Programmed necrosis and necroptosis signalling
Feoktistova, M., & Leverkus, M. (2014) · FEBS Journal · doi:10.1111/febs.13120 · Cited by 153 · see citing works
Gut mucosal DAMPs in IBD: from mechanisms to therapeutic implications
Boyapati, R. K., Rossi, A. G., Satsangi, J., & Ho, G. (2016) · Mucosal Immunology · doi:10.1038/mi.2016.14 · Cited by 148 · see citing works
Nonapoptotic cell death in acute kidney injury and transplantation
Linkermann, A. (2016) · Kidney International · doi:10.1016/j.kint.2015.10.008 · Cited by 140 · see citing works
Cell death checkpoints in the TNF pathway
Huyghe, J., Priem, D., & Bertrand, M. J. M. (2023) · Trends in Immunology · doi:10.1016/j.it.2023.05.007 · Cited by 143 · see citing works
The Two Faces of Receptor Interacting Protein Kinase-1
Weinlich, R., & Green, D. R. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.11.001 · Cited by 127 · see citing works
Self-citation
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
Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver injury
Deutsch, M., Graffeo, C. S., Rokosh, R. S., Pansari, M., Ochi, A., Levie, E., Heerden, E. V., Tippens, D. M., Greco, S., Barilla, R., et al. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.126 · Cited by 131 · see citing works
Caspase‐8: not so silently deadly
Feltham, R., Vince, J. E., & Lawlor, K. E. (2017) · Clinical & Translational Immunology · doi:10.1038/cti.2016.83 · Cited by 123 · see citing works
The in vivo evidence for regulated necrosis
Tonnus, W., & Linkermann, A. (2017) · Immunological Reviews · doi:10.1111/imr.12551 · Cited by 109 · see citing works
Necroptosis and parthanatos are involved in remote lung injury after receiving ischemic renal allografts in rats
Zhao, H., Ning, J., Lemaire, A., Koumpa, F. S., Sun, J. J., Fung, A., Gu, J., Yi, B., Lu, K., & Ma, D. (2014) · Kidney International · doi:10.1038/ki.2014.388 · Cited by 106 · see citing works
Protease signaling in animal and plant‐regulated cell death
Salvesen, G. S., Hempel, A., & Coll, N. S. (2015) · FEBS Journal · doi:10.1111/febs.13616 · Cited by 104 · see citing works
Mitochondrial regulation of cell death: a phylogenetically conserved control
Galluzzi, L., Kepp, O., & Kroemer, G. (2016) · Microbial Cell · doi:10.15698/mic2016.03.483 · Cited by 106 · see citing works
The Inflammatory Signal Adaptor RIPK3: Functions Beyond Necroptosis
Moriwaki, K., & Chan, F. K.-M. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2016.08.007 · Cited by 102 · see citing works
TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1
Etemadi, N., Chopin, M., Anderton, H., Tanzer, M. C., Rickard, J. A., Abeysekera, W., Hall, C. M., Spall, S. K., Wang, B. H., Xiong, Y., et al. (2015) · eLife · doi:10.7554/elife.10592 · Cited by 102 · see citing works
LUBAC prevents lethal dermatitis by inhibiting cell death induced by TNF, TRAIL and CD95L
Taraborrelli, L., Peltzer, N., Montinaro, A., Kupka, S., Rieser, E., Hartwig, T., Sarr, A., Darding, M., Dráber, P., Haas, T. L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06155-8 · Cited by 100 · see citing works
Questions and controversies: the role of necroptosis in liver disease
Dara, L., Liu, Z., & Kaplowitz, N. (2016) · Cell Death Discovery · doi:10.1038/cddiscovery.2016.89 · Cited by 100 · see citing works
FLIP as a therapeutic target in cancer
Humphreys, L. M., Espona‐Fiedler, M., & Longley, D. B. (2018) · FEBS Journal · doi:10.1111/febs.14523 · Cited by 83 · see citing works
Critical function of the necroptosis adaptor RIPK3 in protecting from intestinal tumorigenesis
Bozec, D., Iuga, A. C., Roda, G., Dahan, S., & Yeretssian, G. (2016) · Oncotarget · doi:10.18632/oncotarget.10135 · Cited by 83 · see citing works
cFLIP Regulates Skin Homeostasis and Protects against TNF-Induced Keratinocyte Apoptosis
Panayotova‐Dimitrova, D., Feoktistova, M., Ploesser, M., Kellert, B., Hupe, M., Horn, S., Makarov, R., Jensen, F., Porubský, Š., Schmieder, A., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.09.035 · Cited by 77 · see citing works
Caspase-8 and FADD prevent spontaneous ZBP1 expression and necroptosis
Rodríguez, D. A., Quarato, G., Liedmann, S., Tummers, B., Zhang, T., Guy, C. S., Crawford, J. C., Palacios, G. F., Pelletier, S. W., Kalkavan, H., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2207240119 · Cited by 78 · see citing works
Self-citation
The Inflammatory Caspases-1 and -11 Mediate the Pathogenesis of Dermatitis in Sharpin-Deficient Mice
Douglas, T., Champagne, C., Morizot, A., Lapointe, J., & Saleh, M. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500542 · Cited by 74 · see citing works
ABIN3 Negatively Regulates Necroptosis-induced Intestinal Inflammation Through Recruiting A20 and Restricting the Ubiquitination of RIPK3 in Inflammatory Bowel Disease
Zhou, 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 72 · see citing works
NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells
Alrefai, H., Muhammad, K., Rudolf, R., Pham, D. A. T., Klein‐Hessling, S., Patra, A. K., Avots, A., Bukur, V., Şahin, U., Tenzer, S., et al. (2016) · Nature Communications · doi:10.1038/ncomms11724 · Cited by 72 · see citing works
Cryo-EM structural analysis of FADD:Caspase-8 complexes defines the catalytic dimer architecture for co-ordinated control of cell fate
Fox, J. L., Hughes, M. A., Meng, X., Sarnowska, N. A., Powley, I. R., Jukes‐Jones, R., Dinsdale, D. D., Ragan, T. J., Fairall, L., Schwabe, J. W. R., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20806-9 · Cited by 67 · see citing works
Caspase-8 auto-cleavage regulates programmed cell death and collaborates with RIPK3/MLKL to prevent lymphopenia
Li, X., Li, F., Zhang, X., Zhang, H., Zhao, Q., Li, M., Wu, X., Wang, L., Liu, J., Wu, X., et al. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-00938-9 · Cited by 68 · see citing works
Inhibition of Necroptosis Attenuates Kidney Inflammation and Interstitial Fibrosis Induced By Unilateral Ureteral Obstruction
Xiao, X., Du, C., Yan, Z., Shi, Y., Duan, H., & Ren, Y. (2017) · American Journal of Nephrology · doi:10.1159/000478746 · Cited by 60 · see citing works
DED or alive: assembly and regulation of the death effector domain complexes
Riley, J. S., Malik, A., Holohan, C., & Longley, D. B. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.213 · Cited by 57 · see citing works
STING induces ZBP1-mediated necroptosis independently of TNFR1 and FADD
Kelepouras, K., Saggau, J., Bonasera, D., Kiefer, C., Locci, F., Rakhsh-Khorshid, H., Grauvogel, L., Varanda, A. B., Peifer, M., Loricchio, E., et al. (2025) · Nature · doi:10.1038/s41586-025-09536-4 · Cited by 57 · see citing works
Airway epithelial cell necroptosis contributes to asthma exacerbation in a mouse model of house dust mite-induced allergic inflammation
Oikonomou, N., Schuijs, M. J., Chatzigiagkos, A., Androulidaki, A., Aidinis, V., Hammad, H., Lambrecht, B. N., & Pasparakis, M. (2021) · Mucosal Immunology · doi:10.1038/s41385-021-00415-5 · Cited by 55 · see citing works
cFLIPL acts as a suppressor of TRAIL- and Fas-initiated inflammation by inhibiting assembly of caspase-8/FADD/RIPK1 NF-κB-activating complexes
Davidovich, P. B., Higgins, C. A., Najda, Z., Longley, D. B., & Martin, S. J. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113476 · Cited by 57 · see citing works
Linear ubiquitination of cFLIP induced by LUBAC contributes to TNFα-induced apoptosis
Tang, Y., Joo, D., Liu, G., Tu, H., You, J., Jin, J., Zhao, X., Hung, M., & Lin, X. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005449 · Cited by 49 · see citing works
The interplay of autophagy and non-apoptotic cell death pathways
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2019.12.004 · Cited by 50 · see citing works
Necroptosis in inflammatory bowel disease and other intestinal diseases
Li, S., Ning, L., Lou, X., & Xu, G. (2018) · World Journal of Clinical Cases · doi:10.12998/wjcc.v6.i14.745 · Cited by 49 · see citing works
Inflammatory cell death in intestinal pathologies
Sharma, D., & Kanneganti, T. (2017) · Immunological Reviews · doi:10.1111/imr.12602 · Cited by 48 · see citing works
Self-citation
Balance between short and long isoforms of cFLIP regulates Fas-mediated apoptosis in vivo
Ram, D. R., Ilyukha, V., Volkova, T. O., Buzdin, A. A., Tai, A., Smirnova, I., & Poltorak, A. N. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1517562113 · 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
The Receptor Interacting Protein Kinases in the Liver
Dara, L. (2018) · Seminars in Liver Disease · doi:10.1055/s-0038-1629924 · Cited by 43 · see citing works
TRAIL-coated lipid-nanoparticles overcome resistance to soluble recombinant TRAIL in non-small cell lung cancer cells
de Miguel, D., Gallego-Lleyda, A., Ayuso, J. M., Erviti-Ardanaz, S., Pazo-Cid, R., del Agua, C., Fernández, L. J., Ochoa, I., Anel, A., & Martínez‐Lostao, L. (2016) · Nanotechnology · doi:10.1088/0957-4484/27/18/185101 · Cited by 40 · see citing works
Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency
Oda, H., Manthiram, K., Chavan, P. P., Rieser, E., Veli, Ö., Kaya, Ö., Rauch, C. T., Nakabo, S., Kuehn, H. S., Swart, M., et al. (2024) · Nature Immunology · doi:10.1038/s41590-024-01817-w · Cited by 40 · see citing works
Characterization of the Ripoptosome and Its Components
Schilling, R., Geserick, P., & Leverkus, M. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-801430-1.00004-4 · Cited by 38 · see citing works
Necroptosis in Nonalcoholic Steatohepatitis
Gautheron, J., Vucur, M., & Luedde, T. (2015) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2015.02.001 · Cited by 35 · see citing works
Prix Fixe: Efferocytosis as a Four-Course Meal
Martinez, J. (2015) · Current topics in microbiology and immunology · doi:10.1007/82_2015_467 · Cited by 33 · see citing works
CXCR4 Promotes Renal Tubular Cell Survival in Male Diabetic Rats: Implications for Ligand Inactivation in the Human Kidney
Siddiqi, F. S., Chen, L.-H., Advani, S. L., Thai, K., Batchu, S. N., Alghamdi, T. A., White, K., Sood, M. M., Gibson, I. W., Connelly, K. A., et al. (2014) · Endocrinology · doi:10.1210/en.2014-1650 · Cited by 32 · see citing works
Targeting intestinal epithelial cell–programmed necrosis alleviates tissue injury after intestinal ischemia/reperfusion in rats
Li, X., Ling, Y., Cao, Z., Shen, J., Chen, S., Liu, W., Yuan, B.-L., & Wen, S. (2018) · Journal of Surgical Research · doi:10.1016/j.jss.2018.01.007 · Cited by 31 · see citing works
Epithelial Cell Death and Inflammation in Skin
Kumari, S., & Pasparakis, M. (2015) · Current topics in microbiology and immunology · doi:10.1007/82_2015_466 · Cited by 31 · see citing works
Classification, Scoring, and Quantification of Cell Death in Tissue Sections
Janke, L. J., Ward, J. M., & Vogel, P. (2018) · Veterinary Pathology · doi:10.1177/0300985818800026 · Cited by 29 · see citing works
Self-citation
Role of programmed necrosis and cell death in intestinal inflammation
Dagenais, M., Douglas, T., & Saleh, M. (2014) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000117 · Cited by 29 · see citing works
Cloaked in ubiquitin, a killer hides in plain sight: the molecular regulation of RIPK 1
Justus, S. J., & Ting, A. T. (2015) · Immunological Reviews · doi:10.1111/imr.12304 · Cited by 27 · see citing works
Developmental checkpoints guarded by regulated necrosis
Dillon, C. P., Tummers, B., Baran, K., & Green, D. R. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2188-z · Cited by 26 · see citing works
Self-citation
Caspase‐8 in endothelial cells maintains gut homeostasis and prevents small bowel inflammation in mice
Tisch, N., Mogler, C., Stojanovic, A., Luck, R., Korhonen, E. A., Ellerkmann, A., Adler, H., Singhal, M., Schermann, G., Erkert, L., et al. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202114121 · Cited by 26 · see citing works
An updated view on the functions of caspases in inflammation and immunity
Songane, M., Khair, M., & Saleh, M. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.01.001 · Cited by 25 · see citing works
Irigenin sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells
Xu, Y., Gao, C., Pan, Z., & Zhou, C. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.01.003 · Cited by 25 · see citing works
RNF31 Regulates Skin Homeostasis by Protecting Epidermal Keratinocytes from Cell Death
Tang, Y., Tu, H., Liu, G., Zheng, G., Wang, M., Li, L., Zhao, X., & Lin, X. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800172 · Cited by 23 · see citing works
Cellular FADD-like IL-1β-converting enzyme-inhibitory protein attenuates myocardial ischemia/reperfusion injury via suppressing apoptosis and autophagy simultaneously
Liu, D., Wu, H., Li, Y. Z., Yang, J., Yang, J. M., Ding, J. W., Zhou, G., Zhang, J., Wang, X., & Fan, Z. X. (2021) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2021.02.026 · Cited by 24 · see citing works
Targeting caspase-8: a new strategy for combating hepatocellular carcinoma
Chen, H., Lin, Y., Chen, J., Luo, X., Kan, Y., He, Y., Zhu, R., Jin, J., Li, D., Wang, Y., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1501659 · Cited by 23 · see citing works
Association of autoimmunity and cancer: An emphasis on proteolytic enzymes
Tabrez, S. S. M., Jabir, N. R., Khan, M. I., Khan, M. S., Shakil, S., Siddiqui, A. N., Zaidi, S. K., Ahmed, A. B. A., & Kamal, M. A. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.05.006 · Cited by 23 · see citing works
Necroptotic movers and shakers: cell types, inflammatory drivers and diseases
Weir, A. L., Hughes, S. A., Rashidi, M., Hildebrand, J. M., & Vince, J. E. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2020.09.008 · Cited by 22 · see citing works
Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair
Lagunas, K. M., Savcigil, D. P., Zrilić, M., Fraile, C. C., Craxton, A., Self, E. L., Uranga-Murillo, I., de Miguel, D., Arias, M. A., Willenborg, S., et al. (2023) · Science Advances · doi:10.1126/sciadv.adg2829 · Cited by 24 · see citing works
A critical role for cellular inhibitor of protein 2 (cIAP2) in colitis-associated colorectal cancer and intestinal homeostasis mediated by the inflammasome and survival pathways
Dagenais, M., Dupaul-Chicoine, J., Champagne, C., Skeldon, A. M., Morizot, A., & Saleh, M. (2015) · Mucosal Immunology · doi:10.1038/mi.2015.46 · Cited by 24 · see citing works
Citrullinated myelin induces microglial TNFα and inhibits endogenous repair in the cuprizone model of demyelination
Standiford, M. M., Grund, E. M., & Howe, C. L. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02360-3 · Cited by 23 · see citing works
RIPK3 promoter hypermethylation in hepatocytes protects from bile acid-induced inflammation and necroptosis
Hoff, J. S., Xiong, L., Kammann, T., Neugebauer, S., Micheel, J., Ghait, M., Deshmukh, S. D., Gaßler, N., Bauer, M. W., & Press, A. T. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05794-0 · Cited by 22 · see citing works
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 21 · see citing works
Self-citation
TNF-R1 Cellular Nanovesicles Loaded on the Thermosensitive F-127 Hydrogel Enhance the Repair of Scalded Skin
Xi, L., Wang, L., Zhang, M., He, C., Yang, X., Pang, Y., Chen, H., & Cheng, F. (2023) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.2c01257 · Cited by 21 · see citing works
MLKL deficiency inhibits DSS-induced colitis independent of intestinal microbiota
Zhang, J., Qin, D., Yang, Y., Hu, G., Qin, X., Du, C., & Chen, W. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.01.018 · Cited by 20 · see citing works
Emerging Roles for RIPK1 and RIPK3 in Pathogen-Induced Cell Death and Host Immunity
Saleh, D., & Degterev, A. (2015) · Current topics in microbiology and immunology · doi:10.1007/82_2015_449 · Cited by 19 · see citing works
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 · see citing works
Unfolded protein response transcription factor XBP1 suppresses necroptosis-induced colitis by reinforcing the mucus barrier
Kaya, G. G., Schwarzer, R., Dannappel, M., Vlantis, K., Göbel, U., Kondylis, V., Nedospasov, S. A., & Pasparakis, M. (2025) · Immunity · doi:10.1016/j.immuni.2025.07.023 · Cited by 16 · see citing works
Breaking bad: necroptosis in the pathogenesis of gastrointestinal diseases
Patankar, J. V., Bubeck, M., Acera, M. G., & Becker, C. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1203903 · Cited by 16 · see citing works

Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
Oberst, A., Dillon, C. P., Weinlich, R., McCormick, L. L., Fitzgerald, P., Pop, C., Hakem, R., Salvesen, G. S., & Green, D. R. (2011) · Nature · doi:10.1038/nature09852 · Cited by 1,278 · see citing works
Self-citation
Abstract SY27-01: Cutting both ways: Why FADD, FLIP, and Caspase-8 are required for embryonic development
Green, D. R. (2012) · Cancer Research · doi:10.1158/1538-7445.am2012-sy27-01
Self-citation
Caspase-8 deficiency in mouse embryos triggers chronic RIPK1-dependent activation of inflammatory genes, independently of RIPK3
Kang, T., Jeong, J.-S., Yang, S., Kovalenko, A., & Wallach, D. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0104-9 · Cited by 39 · see citing works
RIP3 mediates the embryonic lethality of caspase-8-deficient mice
Kaiser, W. J., Upton, J. W., Long, A. B., Livingston-Rosanoff, D., Daley-Bauer, L. P., Hakem, R., Caspary, T., & Mocarski, E. S. (2011) · Nature · doi:10.1038/nature09857 · Cited by 1,057 · see citing works
Survival Function of the FADD-CASPASE-8-cFLIPL Complex
Dillon, C. P., Oberst, A., Weinlich, R., Janke, L. J., Kang, T.-B., Ben-Moshe, T., Mak, T. W., Wallach, D., & Green, D. R. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.03.010 · Cited by 331 · see citing works
Self-citation

Authors: Weinlich, R., Oberst, A., Dillon, C. P., Janke, L. J., Milasta, S., Lukens, J. R., Rodriguez, D. A., Gurung, P., Savage, C., Kanneganti, T. D., & Green, D. R.
Affiliations: St. Jude Children's Research Hospital (US)
University of Washington (US)
Corresponding author: Green, Douglas R.
ORCID: Weinlich, Ricardo
Oberst, Andrew
Dillon, Christopher P.
Janke, Laura J.
Lukens, John R.
Gurung, Prajwal
Kanneganti, Thirumala D.
Green, Douglas R.
Venue: Cell Reports
Publisher: Elsevier BV
Published: 2013-10
Volume: 5
Issue: 2
Pages: 340-348
ISSN: 2211-1247 (ISSN-L)
DOI: 10.1016/j.celrep.2013.08.045
PMC: PMC3843376
OpenAlex: W1981860684
Cited by: 157
References: 43
Citations by year: 2026: 5 · 2025: 6 · 2024: 8 · 2023: 12 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 12 · 2018: 18 · 2017: 12 · 2016: 25 · 2015: 22 · 2014: 15 · 2013: 1
FWCI: 9.41
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/3.0/ (vor)
Locations: Cell Reports (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Friedreich's Ataxia Research Alliance
American Lebanese Syrian Associated Charities
National Cancer Institute (R01CA169291, CA169291, P30CA021765)
National Institute of Allergy and Infectious Diseases (R01AI044828, AI47891, AI44828, R01AI047891, 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, c-FLIP, RIPK3, necroptosis, keratinocyte death, tissue homeostasis, sepsis, skin inflammation, intestinal inflammation, TNF-α, embryonic lethality
MeSH terms: Animals, Homeostasis, Neutrophils, Skin, Tamoxifen, Tumor Necrosis Factor-alpha, Apoptosis, Mice, Knockout, Enterocytes, Mice, Caspase 8, Receptor-Interacting Protein Serine-Threonine Kinases, CASP8 and FADD-Like Apoptosis Regulating Protein

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Protective Roles for Caspase-8 and cFLIP in Adult Homeostasis

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks