The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition
Open accessAbstract
Significance: The protein kinase receptor interacting protein 1 controls signaling via death receptors, Toll-like receptors, and retinoic acid-inducible gene 1-like receptors, dictating inflammatory outcomes as broad as cytokine activation and cell death. RIP1 makes a vital contribution during development, evident from the fact that RIP1-deficient mice die soon after birth. Here, we show that a kinase-independent function of RIP1 dampens the consequences of innate immune cell death. During parturition, RIP1 prevents the lethal consequences of RIP3-dependent necroptosis as well as caspase 8 (Casp8)-dependent apoptosis. In contrast to the RIP1-deficient phenotype, mice lacking a combination of RIP1, RIP3, and Casp8 are born and mature into viable, fertile, and immunocompetent adults. These results demonstrate the important protective role of RIP1 against physiologic and microbial death cues encountered at birth.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“Moreover, Ripk1−/− cells display increased sensitivity to necroptosis and/or extrinsic apoptosis induced by a set of innate immune stimuli [499].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [499]
In the citing paper
“Intriguingly, the pro-survival role of RIPK1 in development seems to be independent of both its kinase activity and RIPK3 binding, as demonstrated by the fact that mice genetically engineered to express a kinase-dead variant of RIPK1 (e.g., RIPK1K45A) are viable and fertile [447, 499, 508].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [499]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
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
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
Crosstalk in NF-κB Signaling Pathways
Oeckinghaus, A., Hayden, M. S., & Ghosh, S. (2011) · Nature Immunology · doi:10.1038/ni.2065 · Cited by 1,942
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 2×
“RIP1 remains a component of a death receptor-free cytosolic complex, termed complex II (also called the ripoptosome) (1–3), together with FADD, Casp8, and cFLIP where cFLIP levels control Casp8 activation (13) and death (14).”
BackgroundThe 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
The Death Domain Kinase RIP Mediates the TNF-Induced NF-κB Signal
Kelliher, M. A., Grimm, S., Ishida, Y., Kuo, F., Stanger, B. Z., & Leder, P. (1998) · Immunity · doi:10.1016/s1074-7613(00)80535-x · Cited by 1,102
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
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
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
Self-citation
Cited by
Sorted by citations
Items 101–200 of 291
ZBP1/DAI Drives RIPK3-Mediated Cell Death Induced by IFNs in the Absence of RIPK1
Ingram, J. P., Thapa, R. J., Fisher, A. D., Tummers, B., Zhang, T., Yin, C., Rodríguez, D. A., Guo, H., Lane, R. K., Williams, R. M., et al. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1900216 · Cited by 108
“Early-passage Ripk1 (3), Ripk1Ripk3 (4, 5), Zbp1 (7), and Ripk1Zbp1 murine embryo fibroblasts (MEFs) were generated inhouse from E14.”
BackgroundMethodResultInfluentialSelf-citationNecroptosis: The Trojan horse in cell autonomous antiviral host defense
Mocarski, E. S., Guo, H., & Kaiser, W. J. (2015) · Virology · doi:10.1016/j.virol.2015.03.016 · Cited by 108
“…understood that midgestational death due to germ line deficiency in Casp8 (or FADD) is due to canonical RIP1-RIP3 necroptosis, particularly because the phenotype is reversed by either kinase-inactive RIP3 (Mandal et al., 2014; Newton et al., 2014) or kinase-inactive RIP1 (Kaiser et al., 2014).”
BackgroundInfluentialSelf-citationCurrent translational potential and underlying molecular mechanisms of necroptosis
Molnár, T., Mázló, A., Tslaf, V., Szöllősi, A. G., Emri, G., & Koncz, G. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-2094-z · Cited by 110
Roderick, J. E., Hermance, N. M., Zelic, M., Simmons, M. J., Polykratis, A., Pasparakis, M., & Kelliher, M. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409389111 · Cited by 101
“In addition to TNF, RIPK1-deficient MEF are sensitive to necroptosis induced by type I or type II IFN treatment (24, 25, 43).”
BackgroundResultInfluentialManipulation 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
“1 3 consequence of such pathogen–host détente is a propensity for untoward developmental and immunological defects arising from an imbalance in key ripoptosome components [35, 38, 41, 42].”
BackgroundSelf-citationLi, X., Zhang, M., Huang, X., Liang, W. P., Li, G., Lu, X., Li, Y., Pan, H., Shi, L., Zhu, H., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19935-y · Cited by 99
Necroptosis-independent signaling by the RIP kinases in inflammation
Moriwaki, K., & Chan, F. K.-M. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2203-4 · Cited by 99
Immunological consequences of kidney cell death
Sarhan, M., von Mäßenhausen, A., Hugo, C., Oberbauer, R. W., & Linkermann, A. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0057-9 · Cited by 100
Zhang, X., Fan, C., Zhang, H., Zhao, Q., Liu, Y., Xu, C., Xie, Q., Wu, X., Yu, X., Zhang, J., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.103 · Cited by 93
“The death of Fadd / or Casp8 / embryo can be rescued by co-deletion of Ripk1; however, similar to Ripk1 / mice, these mice die perinatally (Zhang et al., 2011; Rickard et al., 2014; Dillon et al., 2014; Kaiser et al., 2014; Kelliher et al., 1998).”
InfluentialZhang, X., Zhang, H., Xu, C., Li, M., Li, M., Pu, W., Pu, W., Zhou, B., Wang, H., Li, D., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11839-w · Cited by 94
RIP kinase 1–dependent endothelial necroptosis underlies systemic inflammatory response syndrome
Zelic, M., Roderick, J. E., O’Donnell, J. A., Lehman, J. W., Lim, S. E., Janardhan, H. P., Trivedi, C. M., Pasparakis, M., & Kelliher, M. A. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96147 · Cited by 93
Mannion, J., Gifford, V., Bellenie, B. R., Fernando, W., Garcia, L. R., Wilson, R., John, S. W., Udainiya, S., Patin, E. C., Tiu, C., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.04.025 · Cited by 92
Self-citationThe microbiota influences cell death and microglial colonization in the perinatal mouse brain
Castillo-Ruiz, A., Mosley, M., George, A. J., Mussaji, L. F., Fullerton, E. F., Ruszkowski, E. M., Jacobs, A. J., Gewirtz, A. T., Chassaing, B., & Forger, N. G. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.08.027 · Cited by 91
“Parturition is associated with an acute phase inflammatory response in the newborn (Kaiser et al., 2014; Marchini et al., 2000) but it was unknown whether this response is triggered by microbial exposure at birth, or whether it extends to the central nervous system.”
Hildebrand, J. M., Kauppi, M., Majewski, I. J., Liu, Z., Cox, A., Miyake, S., Petrie, E. J., Silk, M. A., Li, Z., Tanzer, M. C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16819-z · Cited by 94
Roles of RIPK1 as a stress sentinel coordinating cell survival and immunogenic cell death
Clucas, J., & Meier, P. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00623-w · Cited by 96
“Likewise, pharmacological inhibition of RIPK1 also impacts both kinase and scaffolding functions, effectively shutting down complex II/ripoptosome formation and concomitantly blocking caspase 8-driven apoptosis or RIPK3-mediated necroptosis 45–49 .”
BackgroundThe role of caspase-8 in inflammatory signalling and pyroptotic cell death
Pang, J., & Vince, J. E. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101832 · Cited by 90
Liu, X., Li, Y., Peng, S., Yu, X., Li, W., Shi, F., Luo, X., Tang, M., Tan, Z., Bode, A. M., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0081-9 · Cited by 91
RIP Kinases in Liver Cell Death, Inflammation and Cancer
Kondylis, V., & Pasparakis, M. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.10.007 · Cited by 85
Necroptosis and its role in infectious diseases
Xia, X., Lei, L., Wang, S., Hu, J., & Zhang, G. (2020) · APOPTOSIS · doi:10.1007/s10495-019-01589-x · Cited by 83
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 85
“RIPK1 also procures cell survival during intestinal injury and inflammation in response to innate immune signals and cytokines such as TNFα, IFNβ, IFNγ, and the TLR3 ligand Poly (I:C) [17-20].”
BackgroundAn Overview of Pathways of Regulated Necrosis in Acute Kidney Injury
Kers, J., Leemans, J. C., & Linkermann, A. (2016) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2016.03.002 · Cited by 80
“Clearly, RIPK1 was shown to be required to prevent spontaneous RIPK3-oligomerization (Kearney et al., 2014; Orozco et al., 2014) and this function must be independent of the kinase domain of RIPK1 (Dillon et al., 2014; Kaiser et al., 2014; Rickard et al., 2014; Roderick et al., 2014).”
BackgroundRIPK1 can function as an inhibitor rather than an initiator of RIPK3‐dependent necroptosis
Kearney, C. J., Cullen, S. P., Clancy, D. M., & Martin, S. J. (2014) · FEBS Journal · doi:10.1111/febs.13034 · Cited by 85
Hänggi, K., Vasilikos, L., Valls, A. F., Yerbes, R., Knop, J., Spilgies, L. M., Rieck, K., Misra, T., Bertin, J., Gough, P. J., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.20 · Cited by 76
“35,36 However, as RIPK1 has been shown to have alternative function in regulating apoptosis and necroptosis 37 – 39 and also directly influencing inflammation, 24,40,41 further downstream effectors of necroptosis such as the use of Mlkl − / − mice are required to prove the role of necroptosis.”
Self-citationThe Autophagy-Initiating Kinase ULK1 Controls RIPK1-Mediated Cell Death
Wu, W., Wang, X., Berleth, N., Deitersen, J., Wallot-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 72
Genetic Regulation of RIPK1 and Necroptosis
Xu, D., Zou, C., & Yuan, J. (2021) · Annual Review of Genetics · doi:10.1146/annurev-genet-071719-022748 · Cited by 80
Die Another Day: Inhibition of Cell Death Pathways by Cytomegalovirus
Brune, W., & Andoniou, C. E. (2017) · Viruses · doi:10.3390/v9090249 · Cited by 77
Generation of small molecules to interfere with regulated necrosis
Degterev, A., & Linkermann, A. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2198-x · Cited by 72
“, in response to IFN or TLR signals [53, 61], and in vivo during mammalian parturition [74].”
BackgroundThe role of regulated necrosis in endocrine diseases
Tonnus, W., Belavgeni, A., Beuschlein, F., Eisenhofer, G., Faßnacht, M., Kroiß, M., Krone, N. P., Reincke, M., Bornstein, S. R., & Linkermann, A. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00499-w · Cited by 74
Shutinoski, B., Alturki, N. A., Rijal, D., Bertin, J., Gough, P. J., Schlossmacher, M. G., & Sad, S. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.51 · Cited by 71
“appears to have a scaffolding function, which may influence immune homeostasis.(6,7) Depending on the interacting partners and posttranslational modifications, RIPK1 has a multifaceted role in cell signaling and cell survival.”
BackgroundSelf-citationPhenytoin inhibits necroptosis
von Mäßenhausen, A., Tonnus, W., Himmerkus, N., Parmentier, S. P., Saleh, D., Rodríguez, D. A., Ousingsawat, J., Ang, R. L., Weinberg, J. M., Sanz, A. B., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0394-3 · Cited by 75
Self-citationNi, H., Chao, X., Kaseff, J., Deng, F., Wang, S., Shi, Y., Li, T., Ding, W., & Jaeschke, H. (2019) · American Journal Of Pathology · doi:10.1016/j.ajpath.2019.03.010 · Cited by 72
“Peter Gough (GlaxoSmithKline, Research Triangle Park, NC).(27,28) Briefly, Ripk3 KDKI mice were generated by homologous recombination using a targeting construct that mutated the catalytic lysine residue to alanine (K51A) to eliminate all kinase activity.”
MethodUnleashing TNF cytotoxicity to enhance cancer immunotherapy
Freeman, A. J., Kearney, C. J., Silke, J., & Oliaro, J. (2021) · Trends in Immunology · doi:10.1016/j.it.2021.10.003 · Cited by 69
Daley‐Bauer, L. P., Roback, L., Crosby, L. N., McCormick, A. L., Feng, Y., Kaiser, W. J., & Mocarski, E. S. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1616829114 · Cited by 65
“C57BL/6J mice (Jackson Laboratory), Ripk3−/−, DKO (9), KKH (40), Ripk1K45A/K45A (41), and TNFα−/−Dai−/− generated by crossing Dai−/− mice (42) with Tnfα−/− mice (B6;129S-Tnf tm1Gkl/J; Jackson Laboratory) were used in this study.”
MethodInfluentialSelf-citationNecroptosis in heart disease: Molecular mechanisms and therapeutic implications
Guo, X., Chen, Y., & Liu, Q. (2022) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2022.05.006 · Cited by 70
RIPK1 prevents TRADD-driven, but TNFR1 independent, apoptosis during development
Anderton, H., Bandala‐Sanchez, E., Simpson, D. S., Rickard, J. A., Ng, A. P., Rago, L. D., Hall, C. M., Vince, J. E., Silke, J., Liccardi, G., et al. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0166-8 · Cited by 65
RIP3 Regulates Autophagy and Promotes Coxsackievirus B3 Infection of Intestinal Epithelial Cells
Harris, K. G., Morosky, S. A., Drummond, C., Patel, M., Kim, C., Stolz, D. B., Bergelson, J. M., Cherry, S. R., & Coyne, C. B. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.07.007 · Cited by 64
“Whereas RIP1 is required for TNF-a-induced RIP3dependent necroptosis, recent evidence has shown that RIP1 negatively regulates TRIF-mediated, IFN-mediated, and spontaneous RIP3-dependent necroptosis in a kinase-independent fashion (Dillon et al., 2014; Kaiser et al., 2014; Rickard et al., 2014).”
BackgroundFang, T., Yao, J., Yan, M., Sun, X., Wang, W., Gao, W., Tian, Z., Guo, S., Dong, Z., Li, B., et al. (2016) · Scientific Reports · doi:10.1038/srep21992 · Cited by 66
Sharifi, M., Hosseinali, S. H., Saboury, A. A., Szegezdi, É., & Falahati, M. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.02.007 · Cited by 62
Tan, Y., Sementino, E., Cheung, M., Peri, S., Menges, C. W., Kukuyan, A.-M., Zhang, T., Khazak, V., Fox, L. A., Ross, E. A., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3683 · Cited by 63
Self-citationSuda, J., Dara, L., Yang, L., Aghajan, M., Song, Y., Kaplowitz, N., & Liu, Z. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600690 · Cited by 63
Tyrosine Kinase SYK Licenses MyD88 Adaptor Protein to Instigate IL-1α-Mediated Inflammatory Disease
Gurung, P., Fan, G., Lukens, J. R., Vogel, P., Tonks, N. K., & Kanneganti, T. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.014 · Cited by 64
“Therefore to further ascertain the role of RIPK1 in this inflammatory skin disease, we took advantage of Casp8 / 3 Ripk3 / 3 Ripk1 / mice, which were crossed with Ptpn6 mice (Dillon et al., 2014; Kaiser et al., 2014; Rickard et al., 2014).”
InfluentialPtpn6 inhibits caspase-8- and Ripk3/Mlkl-dependent inflammation
Speir, M., Nowell, C. J., Chen, A. A., O’Donnell, J. A., Shamie, I., Lakin, P. R., D’Cruz, A. A., Braun, R. O., Babon, J. J., Lewis, R. S., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0550-7 · Cited by 61
Yin, H., Guo, X., Chen, Y., Zeng, Y., Mo, X., Hong, S., He, H., Li, J., Steinmetz, R. N., & Liu, Q. (2022) · Journal of Clinical Investigation · doi:10.1172/jci152297 · Cited by 57
“We crossed Tab2fl/fl-MerCreMer mice with Ripk1K45A-knockin mice, which carry a RIPK1 kinase-dead K45A (lysine 45 to alanine) mutation (47).”
MethodFrom (Tool)Bench to Bedside: The Potential of Necroptosis Inhibitors
Gardner, C. R., Davies, K. A., Zhang, Y., Brzozowski, M., Czabotar, P. E., Murphy, J. M., & Lessène, G. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01621 · Cited by 60
The RIPK1 death domain restrains ZBP1- and TRIF-mediated cell death and inflammation
Imai, T., Lin, J., Kaya, G. G., Ju, E., Kondylis, V., Kelepouras, K., Liccardi, G., KIM, C. S., & Pasparakis, M. (2024) · Immunity · doi:10.1016/j.immuni.2024.04.016 · Cited by 58
Molecular Cell Biology of Apoptosis and Necroptosis in Cancer
Dillon, C. P., & Green, D. R. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-39406-0_1 · Cited by 62
Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease
Benn, C., & Dawson, L. A. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00242 · Cited by 59
Controlled detonation: evolution of necroptosis in pathogen defense
Brault, M., & Oberst, A. (2016) · Immunology and Cell Biology · doi:10.1038/icb.2016.117 · Cited by 57
Relevance of necroptosis in cancer
Lalaoui, N., & Brumatti, G. (2016) · Immunology and Cell Biology · doi:10.1038/icb.2016.120 · Cited by 56
Proteomic analysis of necroptotic extracellular vesicles
Shlomovitz, I., Erlich, Z., Arad, G., Edry‐Botzer, L., Zargarian, S., Cohen, H., Manko, T., Ofir‐Birin, Y., Cooks, T., Regev‐Rudzki, N., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04317-z · Cited by 55
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 54
CRISPR whole-genome screening identifies new necroptosis regulators and RIPK1 alternative splicing
Callow, M. G., Watanabe, C. K., Wickliffe, K. E., Bainer, R. O., Kummerfeld, S., Weng, J., Cuellar, T. L., Janakiraman, V., Chen, H., Chih, B., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0301-y · Cited by 49
Bone Marrow–Derived RIPK3 Mediates Kidney Inflammation in Acute Kidney Injury
Martin-Sanchez, D., Guerrero-Mauvecin, J., Fontecha‐Barriuso, M., Méndez‐Barbero, N., Saiz, M. L., Lopez-Diaz, A. M., Sánchez-Niño, M. D., Carrasco, S., Cannata-Ortiz, P., Ruiz‐Ortega, M., et al. (2022) · Journal of the American Society of Nephrology · doi:10.1681/asn.2021030383 · Cited by 54
“The efficacy of BM reconstitution was tested by PCR analysis on blood samples with the same primers used for tail Ripk3 genotyping.(27) In all experimental models, plasma samples were collected at the time of euthanasia.”
MethodNecroptosis in acute kidney injury: a shedding light
Wang, S., Zhang, C., Hu, L., & Yang, C. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.37 · Cited by 54
“Recent exciting findings showed that kinase-inactive Rip1 mutant D138N and K45A knockin mice are viable.(30,31) Importantly, in addition, cells derived from these mice are resistant to necroptosis, but mediate NF-κB pathway normally.”
BackgroundMechanical force-mediated pathological cartilage thinning is regulated by necroptosis and apoptosis
Zhang, C., Lin, S., Li, T., Jiang, Y., Huang, Z., Wen, J., Cheng, W., & Li, H. (2017) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2017.03.018 · Cited by 54
Molecular mechanisms of necroptosis and relevance for neurodegenerative diseases.
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2019.12.006 · Cited by 51
Sansone, C., Bruno, A., Piscitelli, C., Baci, D., Fontana, A., Brunet, C., Noonan, D. M., & Albini, A. (2021) · Cells · doi:10.3390/cells10020231 · Cited by 55
Post-translational control of RIPK3 and MLKL mediated necroptotic cell death
Murphy, J. M., & Vince, J. E. (2015) · F1000Research · doi:10.12688/f1000research.7046.1 · Cited by 55
Lü, J., Sun, Z., Fang, Y., Zheng, J., Xu, S., Xu, W., Shi, L., Mei, S., Wu, H., Liang, F., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01360 · Cited by 52
RIPK1 blocks T cell senescence mediated by RIPK3 and caspase-8
Imanishi, T., Unno, M., Yoneda, N., Motomura, Y., Mochizuki, M., Sasaki, T., Pasparakis, M., & Saito, T. (2023) · Science Advances · doi:10.1126/sciadv.add6097 · Cited by 50
“Because RIPK1 blocks caspase-8–dependent apoptosis and RIPK3-dependent necroptosis during development (19, 20), it is likely that caspase-8 and RIPK3 are involved in the increased activation of Akt, mTORC1, and ERK signaling in RIPK1-KO T cells.”
BackgroundRegulation of the release of damage-associated molecular patterns from necroptotic cells
Nakano, H., Murai, S., & Moriwaki, K. (2022) · Biochemical Journal · doi:10.1042/bcj20210604 · Cited by 54
Kinase domain dimerization drives RIPK3-dependent necroptosis
Raju, S., Whalen, D. M., Mengistu, M., Swanson, C. J., Quinn, J. G., Taylor, S. S., Webster, J. D., Newton, K., & Shaw, A. S. (2018) · Science Signaling · doi:10.1126/scisignal.aar2188 · Cited by 48
Death in the fast lane: what's next for necroptosis?
Oberst, A. (2015) · FEBS Journal · doi:10.1111/febs.13520 · Cited by 47
RIPK1 in the inflammatory response and sepsis: Recent advances, drug discovery and beyond
Liu, X., Tang, A.-L., Chen, J., Gao, N., Zhang, G., & Xiao, C. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1114103 · Cited by 48
“Mutations at the K45A site, which result in a loss of kinase activity, protect cells from TNF-astimulated necroptosis (26).”
BackgroundRIP3-mediated necroptosis is regulated by inter-filament assembly of RIP homotypic interaction motif
Hu, H., Wu, X., Wu, G., Nan, N., Zhang, J., Zhu, X., Zhang, Y., Shu, Z., Liu, J., Liu, X., et al. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0598-9 · Cited by 47
25 years of research put RIPK1 in the clinic
Liu, L., & Lalaoui, N. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.08.007 · Cited by 45
RIP1 kinase activity-dependent roles in embryonic development of Fadd-deficient mice
Liu, Y., Fan, C., Zhang, Y., Yu, X., Wu, X., Zhang, X., Zhao, Q., Zhang, H., Xie, Q., Li, M., et al. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.78 · Cited by 42
“necroptosis.(28,29,31,32,36) Although it is required for necroptosis signaling, a role of RIP1 kinase activity of RIP1 on the”
BackgroundThe latest information on the RIPK1 post-translational modifications and functions
Wang, Q., Fan, D., Xia, Y., Ye, Q., Xi, X., Zhang, G., & Xiao, C. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112082 · Cited by 41
Mechanisms of RIPK3‐induced inflammation
Shlomovitz, I., Zargrian, S., & Gerlic, M. (2016) · Immunology and Cell Biology · doi:10.1038/icb.2016.124 · Cited by 43
The Receptor Interacting Protein Kinases in the Liver
Dara, L. (2018) · Seminars in Liver Disease · doi:10.1055/s-0038-1629924 · Cited by 43
Kupka, S., Reichert, M., Dráber, P., & Walczak, H. (2016) · FEBS Journal · doi:10.1111/febs.13644 · Cited by 41
Webb, L. V., Barbarulo, A., Huysentruyt, J., Berghe, T. V., Takahashi, N., Ley, S. C., Vandenabeele, P., & Seddon, B. P. (2019) · Immunity · doi:10.1016/j.immuni.2019.01.004 · Cited by 42
“, 2014) also suggest that thymopoeisis is normal in the absence of death machinery and have peripheral T cells that can mount anti-viral responses (Kaiser et al., 2014).”
BackgroundRIP1 kinase mediates angiogenesis by modulating macrophages in experimental neovascularization
Ueta, T., Ishihara, K., Notomi, S., Lee, J., Maidana, D. E., Efstathiou, N. E., Murakami, Y., Hasegawa, E., Azuma, K., Toyono, T., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908355116 · Cited by 41
RIPK1 Promotes Energy Sensing by the mTORC1 Pathway
Najafov, A., Luu, H. S., Mookhtiar, A. K., Mifflin, L., Xia, H., Amin, P. P., Ordureau, A., Wang, H., & Yuan, J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.11.008 · Cited by 40
ZBP1 and TRIF trigger lethal necroptosis in mice lacking caspase-8 and TNFR1
Solon, M., Ge, N., Hambro, S., Haller, S., Jiang, J. W., Baca, M., Preston, J., Maltzman, A., Wickliffe, K. E., Liang, Y., et al. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-024-01286-6 · Cited by 41
Dendritic Cell RIPK1 Maintains Immune Homeostasis by Preventing Inflammation and Autoimmunity
O’Donnell, J. A., Lehman, J. W., Roderick, J. E., Martinez‐Marin, D., Zelic, M., Doran, C. G., Hermance, N. M., Lyle, S. R., Pasparakis, M., Fitzgerald, K. A., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1701229 · Cited by 39
Development of a RIPK1 degrader to enhance antitumor immunity
Yu, X., Lu, D., Qi, X., Paudel, R. R., Lin, H., Holloman, B. L., Jin, F., Xu, L., Ding, L., Peng, W., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-55006-2 · Cited by 43
Wang, Z., Feng, J., Yu, J., & Chen, G. (2019) · Journal of Cell Science · doi:10.1242/jcs.227777 · Cited by 35
“In addition to TNF-induced phosphorylation ofRIPK1 andRIPK3, the spontaneous phosphorylation of RIPK1 and RIPK3 in the early signaling stage before TNF treatment is also indispensable for necroptosis induction because suppression of RIPK1 and RIPK3 spontaneous phosphorylation through kinase-dead mutation blocks necros…”
BackgroundKinase-independent functions of RIPK1 regulate hepatocyte survival and liver carcinogenesis
Van, T.-M., Polykratis, A., Straub, B. K., Kondylis, V., Papadopoulou, N., & Pasparakis, M. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92508 · Cited by 35
IAP gene deletion and conditional knockout models
Silke, J., & Vaux, D. L. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.12.004 · Cited by 32
Feltham, R., & Silke, J. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.67 · Cited by 33
TRADD regulates perinatal development and adulthood survival in mice lacking RIPK1 and RIPK3
Dowling, J. P., Alsabbagh, M. Y., Casale, C. D., Liu, Z.-G., & Zhang, J. (2019) · Nature Communications · doi:10.1038/s41467-019-08584-5 · Cited by 30
Croker, B. A., Silke, J., & Gerlic, M. (2015) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000148 · Cited by 33
Down the rabbit hole: Is necroptosis truly an innate response to infection?
Pearson, J. S., & Murphy, J. M. (2017) · Cellular Microbiology · doi:10.1111/cmi.12750 · Cited by 28
“…normal mammalian development (Murphy et al., 2013; Newton et al., 2004), although dysregulated necroptosis is known to be deleterious to development (Dillon et al., 2014; Kaiser et al., 2011; Kaiser et al., 2014; Kelliher et al., 1998; Rickard et al., 2014a; Welz et al., 2011; Zhang et al., 1998).”
BackgroundTargeting RIP Kinases in Chronic Inflammatory Disease
Speir, M., Djajawi, T. M., Conos, S. A., Tye, H., & Lawlor, K. E. (2021) · Biomolecules · doi:10.3390/biom11050646 · Cited by 30
Inflammatory cell death induced by cytotoxic lymphocytes: a dangerous but necessary liaison
de Miguel, D., Ramírez-Labrada, A., Uranga-Murillo, I., Hidalgo, S., Santiago, L., Gálvez, E. M., Arias, M. A., & Pardo, J. (2021) · FEBS Journal · doi:10.1111/febs.16093 · Cited by 33
“Therefore, RIPK1 acts as a regulator hub for both 11 apoptosis and necroptosis, especially in TNF signalling [75-77].”
BackgroundLi, J., Yang, K., Pan, X., Peng, H. C., Hou, C., Xiao, J., & Wang, Q. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s361541 · Cited by 29
“Apoptosis is an indispensable physiological process of tissue formation during embryogenesis and even after birth, and it results in the controlled death of the cell without releasing its contents out of the cells.(27) Differed from apoptosis, necroptosis and pyroptosis allow the release of immunogenic cellular conten…”
BackgroundDu, J., & Wang, Z. (2024) · Biomedicines · doi:10.3390/biomedicines12071525 · Cited by 28
“While double-knockout of RIPK3, Caspase-8, or FADD, along with RIPK1, only marginally prolongs survival [102–104], triple-knockout of RIPK1, RIPK3, and either Caspase-8 or FADD rescues RIPK1-deficient mice, allowing them to survive weaning and mature normally [105,106].”
BackgroundZhang, H., Li, X., Li, M., Li, F., Li, F., Wang, L., Zhang, Y., Zhang, Y., Luo, Y., Wang, H., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107650 · Cited by 27
A tale of two domains – a structural perspective of the pseudokinase, MLKL
Czabotar, P. E., & Murphy, J. M. (2015) · FEBS Journal · doi:10.1111/febs.13504 · Cited by 29
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 30
“Interestingly, because of the dual role of RIP1 in apoptosis and necroptosis, Ripk1-/- mice succumb soon after birth, and this perinatal lethality is only rescued by combined deletion of Caspase-8 and Ripk3 [43].”
BackgroundInfluentialCloaked 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
DAI Another Way: Necroptotic Control of Viral Infection
Upton, J. W., & Kaiser, W. J. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.01.016 · Cited by 27
Self-citationDevelopmental 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 28
“2c) [37, 81, 82].”
BackgroundA unique death pathway keeps RIPK1 D325A mutant mice in check at embryonic day 10.5
Zhang, Y., Huang, K., Zhang, Y., Tao, H., Li, L., Ruan, C., Sun, Y.-H., Shi, W., Han, W., Wu, S., et al. (2021) · PLoS Biology · doi:10.1371/journal.pbio.3001304 · Cited by 26
Caspase-8 restricts antiviral CD8 T cell hyperaccumulation
Feng, Y., Daley‐Bauer, L. P., Roback, L., Guo, H., Koehler, H. S., Potempa, M., Lanier, L. L., & Mocarski, E. S. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1904319116 · Cited by 26
“Abnormal B220CD3 T cells accumulate in aging DKO mice (13, 14, 29, 30), a phenomenon that has been ascribed to CASP8 function downstream of FADD signaling (11, 33).”
BackgroundSelf-citationThe interplay between cell death and senescence in cancer
Shimizu, K., Inuzuka, H., & Tokunaga, F. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.11.001 · Cited by 28
Dowling, J. P., Nair, A., & Zhang, J. (2015) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2015.00012 · Cited by 24
RIP kinases and necroptosis in aging and aging-related diseases
Yang, Y., Li, X., Zhang, T., & Xu, D. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac003 · Cited by 27
Unwinding the modalities of necrosome activation and necroptosis machinery in neurological diseases
Gupta, R. V., Kumari, S., Tripathi, R. S., Ambasta, R. K., & Kumar, P. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101855 · Cited by 27
Metadata
- Authors
- Kaiser, W. J., Daley-Bauer, L. P., Thapa, R. J., Mandal, P., Berger, S. B., Huang, C., Sundararajan, A., Guo, H., Roback, L., Speck, S. H., Bertin, J., Gough, P. J., Balachandran, S., & Mocarski, E. S.
- Affiliations
- Emory University (US)
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
- Fox Chase Cancer Center (US)
- GlaxoSmithKline (United States) (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-05-12
- Volume
- 111
- Issue
- 21
- Pages
- 7753-7758
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4040608
- OpenAlex
- W2069250210
- Cited by
- 291
- References
- 41
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 17 · 2023: 14 · 2022: 17 · 2021: 24 · 2020: 28 · 2019: 29 · 2018: 25 · 2017: 26 · 2016: 39 · 2015: 30 · 2014: 22
- FWCI
- 15.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DP5OD012198)
- U.S. Public Health Service (R5630363)
- National Cancer Institute (R01CA168621, T32CA009035)
- National Institute of Allergy and Infectious Diseases (R01AI020211, R21AI104212, R01AI118853)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- RIPK1, RIPK3, caspase-8, necroptosis, apoptosis, innate immunity, childbirth, perinatal lethality, kinase-independent function, TNF-α, interferon, double-stranded RNA, antiviral immunity
- MeSH terms
- Animals, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunity, Innate, Necrosis, Immunoblotting, Signal Transduction, Apoptosis, DNA Primers, Mice, Knockout, GTPase-Activating Proteins, Parturition, Mice, Caspase 8, Receptor-Interacting Protein Serine-Threonine Kinases, Gene Knock-In Techniques
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
