HOIP Deficiency Causes Embryonic Lethality by Aberrant TNFR1-Mediated Endothelial Cell Death
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Linear ubiquitination is crucial for innate and adaptive immunity. The linear ubiquitin chain assembly complex (LUBAC), consisting of HOIL-1, HOIP, and SHARPIN, is the only known ubiquitin ligase that generates linear ubiquitin linkages. HOIP is the catalytically active LUBAC component. Here, we show that both constitutive and Tie2-Cre-driven HOIP deletion lead to aberrant endothelial cell death, resulting in defective vascularization and embryonic lethality at midgestation. Ablation of tumor necrosis factor receptor 1 (TNFR1) prevents cell death, vascularization defects, and death at midgestation. HOIP-deficient cells are more sensitive to death induction by both tumor necrosis factor (TNF) and lymphotoxin-α (LT-α), and aberrant complex-II formation is responsible for sensitization to TNFR1-mediated cell death in the absence of HOIP. Finally, we show that HOIP's catalytic activity is necessary for preventing TNF-induced cell death. Hence, LUBAC and its linear-ubiquitin-forming activity are required for maintaining vascular integrity during embryogenesis by preventing TNFR1-mediated endothelial cell death.
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LUBAC is required for inhibition of TNF-induced cell death.
“which also explains the requirement of LUBAC for the inhibition of TNF-induced cell death [345].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [345]
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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 · see citing works
Manipulating the Mouse Embryo: A Laboratory Manual
Behringer, R. R., Gertsenstein, M., Nagy, K. V., & Nagy, A. (2002) · Cited by 2,046 · see citing works
A conditional knockout resource for the genome-wide study of mouse gene function
Skarnes, W. C., Rosen, B., West, A. P., Koutsourakis, M., Bushell, W., Iyer, V., Mujica, A. O., Thomas, M., Harrow, J., Cox, T., et al. (2011) · Nature · doi:10.1038/nature10163 · Cited by 1,708 · see citing works
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 · see citing works
Rothe, J., Lesslauer, W., Loetscher, H., Lang, Y., Koebel, P., Köntgen, F., Althage, A., Zinkernagel, R. M., Steinmetz, M., & Bluethmann, H. (1993) · Nature · doi:10.1038/364798a0 · Cited by 1,246 · see citing works
Pasparakis, M., Alexopoulou, L., Episkopou, V., & Kollias, G. A. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.4.1397 · Cited by 1,160 · 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
Involvement of linear polyubiquitylation of NEMO in NF-κB activation
Tokunaga, F., Sakata, S., Saeki, Y., Satomi, Y., Kirisako, T., Kamei, K., Nakagawa, T., Kato, M., Murata, S., Yamaoka, S., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1821 · Cited by 943 · see citing works
Linear ubiquitination prevents inflammation and regulates immune signalling
Gerlach, B., Cordier, S. M., Schmukle, A. C., Emmerich, C. H., Rieser, E., Haas, T. L., Webb, A. I., Rickard, J. A., Anderton, H., Wong, W. W.-L., et al. (2011) · Nature · doi:10.1038/nature09816 · Cited by 940 · see citing works
Self-citationFADD: 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
Characterization of receptors for human tumour necrosis factor and their regulation by γ-interferon
Aggarwal, B. B., Eessalu, T. E., & Hass, P. E. (1985) · Nature · doi:10.1038/318665a0 · Cited by 876 · see citing works
The emerging complexity of protein ubiquitination
Komander, D. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370937 · Cited by 821 · see citing works
Tenev, T., Bianchi, K., Darding, M., Broemer, M., Langlais, C., Wållberg, F., Zachariou, A., Lopez, J. S., MacFarlane, M., Cain, K., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.006 · Cited by 818 · see citing works
Self-citationZhang, J., Cado, D., Chen, A., Kabra, N., & Winoto, A. (1998) · Nature · doi:10.1038/32681 · Cited by 792 · see citing works
Haas, T. L., Emmerich, C. H., Gerlach, B., Schmukle, A. C., Cordier, S. M., Rieser, E., Feltham, R., Vince, J. E., Warnken, U. H., Wenger, T., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.10.013 · Cited by 768 · see citing works
Self-citationCharacterization of tumor necrosis factor-deficient mice
Marino, M. W., Dunn, A. R., Grail, D., Inglese, M., Noguchi, Y., Richards, E. A., Jungbluth, A., Wada, H., Moore, M. A. S., Williamson, B., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.8093 · Cited by 767 · see citing works
SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis
Ikeda, F., Deribe, Y. L., Skånland, S. S., Stieglitz, B., Grabbe, C., Franz-Wachtel, M., van Wijk, S. J. L., Goswami, P., Nagy, V., Terzic, J., et al. (2011) · Nature · doi:10.1038/nature09814 · Cited by 745 · see citing works
Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity
Gray, P. W., Aggarwal, B. B., Benton, C. V., Bringman, T. S., Henzel, W. J., Jarrett, J. A., Leung, D. W., Moffat, B., Ng, P., Svedersky, L. P., et al. (1984) · Nature · doi:10.1038/312721a0 · Cited by 641 · see citing works
SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex
Tokunaga, F., Nakagawa, T., Nakahara, M., Saeki, Y., Taniguchi, M., Sakata, S.-I., Tanaka, K., Nakano, H., & Iwai, K. (2011) · Nature · doi:10.1038/nature09815 · Cited by 609 · see citing works
Limb and Skin Abnormalities in Mice Lacking IKKα
Takeda, K., Takeuchi, O., Tsujimura, T., Itami, S., Adachi, O., Kawai, T., Sanjo, H., Yoshikawa, K., Terada, N., & Akira, S. (1999) · Science · doi:10.1126/science.284.5412.313 · Cited by 609 · see citing works
Widespread recombinase expression using FLPeR (Flipper) mice
Farley, F. W., Soriano, P. M., Steffen, L. S., & Dymecki, S. M. (2000) · genesis · doi:10.1002/1526-968x(200011/12)28:3/4 · Cited by 602 · see citing works
Embryonic Lethality, Liver Degeneration, and Impaired NF-κB Activation in IKK-β-Deficient Mice
Tanaka, M., Fuentes, M. E., Yamaguchi, T., Durnin, M., Dalrymple, S. A., Hardy, K. L., & Goeddel, D. V. (1999) · Immunity · doi:10.1016/s1074-7613(00)80042-4 · Cited by 569 · see citing works
Severe liver degeneration and lack of NF-kappaB activation in NEMO/IKKgamma-deficient mice.
Rudolph, D., Yeh, W., Wakeham, A. C., Rudolph, B., Nallainathan, D., Potter, J., Elia, A., & Mak, T. W. (2000) · PubMed Central · Cited by 518 · see citing works
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
Browning, J. L. (1993) · Cell · doi:10.1016/0092-8674(93)90574-a · Cited by 479 · see citing works
Rudolph, D., Yeh, W.-C., Wakeham, A., Rudolph, B., Nallainathan, D., Potter, J., Elia, A. J., & Mak, T. W. (2000) · Genes & Development · doi:10.1101/gad.14.7.854 · Cited by 479 · see citing works
NEMO/IKKγ-Deficient Mice Model Incontinentia Pigmenti
Schmidt‐Supprian, M., Bloch, W., Courtois, G., Addicks, K., Israël, A., Rajewsky, K., & Pasparakis, M. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80263-4 · Cited by 437 · see citing works
Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains
Emmerich, C. H., Ordureau, A., Strickson, S., Arthur, J. S. C., Pedrioli, P. G. A., Komander, D., & Cohen, P. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314715110 · Cited by 433 · 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
Functional complementation between FADD and RIP1 in embryos and lymphocytes
Zhang, H., Zhou, X., McQuade, T. J., Li, J., Chan, F. K.-M., & Zhang, J. (2011) · Nature · doi:10.1038/nature09878 · Cited by 422 · see citing works
A Lymphotoxin-β-Specific Receptor
Crowe, P. D., VanArsdale, T. L., Walter, B. N., Ware, C. F., Hession, C. A., Ehrenfels, B. N., Browning, J. L., Din, W. S., Goodwin, R. G., & Smith, C. A. (1994) · Science · doi:10.1126/science.8171323 · Cited by 389 · see citing works
The Ubiquitin Ligase XIAP Recruits LUBAC for NOD2 Signaling in Inflammation and Innate Immunity
Damgaard, R. B., Nachbur, U., Yabal, M., Wong, W. W.-L., Fiil, B. K., Kastirr, M., Rieser, E., Rickard, J. A., Bankovacki, A., Peschel, C., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.04.014 · Cited by 379 · see citing works
Self-citationDeath before birth: clues from gene knockouts and mutations
Copp, A. J. (1995) · Trends in Genetics · doi:10.1016/s0168-9525(00)89008-3 · Cited by 368 · 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
The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis
Rivkin, E., Almeida, S. M., Ceccarelli, D. F. J., Juang, Y.-C. A., MacLean, T. A., Srikumar, T., Huang, H., Dunham, W. H., Fukumura, R., ., G. X., et al. (2013) · Nature · doi:10.1038/nature12296 · Cited by 280 · see citing works
Haar, J. L., & Ackerman, G. A. (1971) · The Anatomical Record · doi:10.1002/ar.1091700206 · Cited by 273 · see citing works
Ubiquitin in the immune system
Zinngrebe, J., Montinaro, A., Peltzer, N., & Walczak, H. (2014) · The EMBO Reports · doi:10.1002/embr.201338025 · Cited by 227 · see citing works
Self-citationSeymour, R. E., Hasham, M. G., Cox, G. A., Shultz, L. D., HogenEsch, H., Roopenian, D. C., & Sundberg, J. P. (2007) · Genes and Immunity · doi:10.1038/sj.gene.6364403 · Cited by 212 · see citing works
Linear ubiquitin chains: NF-κB signalling, cell death and beyond
Iwaï, K., Fujita, H., & Sasaki, Y. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3836 · Cited by 207 · see citing works
IAPs limit activation of RIP kinases by TNF receptor 1 during development
Moulin, M., Anderton, H., Voss, A. K., Thomas, T., Wong, W. W., Bankovacki, A., Feltham, R., Chau, D., Cook, W. D., Silke, J., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.18 · Cited by 193 · see citing works
Self-citationKnockout mouse models to study Wnt signal transduction
van Amerongen, R., & Berns, A. J. M. (2006) · Trends in Genetics · doi:10.1016/j.tig.2006.10.001 · Cited by 181 · see citing works
RIPK-Dependent Necrosis and Its Regulation by Caspases: A Mystery in Five Acts
Green, D. R., Oberst, A., Dillon, C. P., Weinlich, R., & Salvesen, G. S. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.09.003 · Cited by 169 · see citing works
Generation and physiological roles of linear ubiquitin chains
Walczak, H., Iwaï, K., & Đikić, I. (2012) · BMC Biology · doi:10.1186/1741-7007-10-23 · Cited by 167 · see citing works
Self-citationLinear ubiquitination: a newly discovered regulator of cell signalling
Rieser, E., Cordier, S. M., & Walczak, H. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.11.007 · Cited by 159 · see citing works
Self-citationFolic acid prevents exencephaly in Cited2 deficient mice
Martı́nez-Barberá, J. P. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.3.283 · Cited by 153 · see citing works
Gustafsson, E., Brakebusch, C., Hietanen, K., & Fässler, R. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.4.671 · Cited by 149 · see citing works
Defective immune responses in mice lacking LUBAC‐mediated linear ubiquitination in B cells
Sasaki, Y., Sano, S., Nakahara, M., Murata, S., Kometani, K., Aiba, Y., Sakamoto, S., Watanabe, Y., Tanaka, K., Kurosaki, T., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.184 · Cited by 126 · see citing works
Etemadi, N., Holien, J. K., Chau, D., Dewson, G., Murphy, J. M., Alexander, W. S., Parker, M. W., Silke, J., & Nachbur, U. (2013) · FEBS Journal · doi:10.1111/febs.12419 · Cited by 73 · see citing works
Self-citationZak, D. E., Schmitz, F., Gold, E. S., Diercks, A. H., Peschon, J. J., Valvo, J., Niemistö, A., Podolsky, I., Fallen, S., Suen, R., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1107577108 · Cited by 66 · see citing works
Murphy, J. M., & Silke, J. (2014) · EMBO Reports · doi:10.1002/embr.201337970 · Cited by 66 · see citing works
Self-citationInlay, M. A., Serwold, T. F., Mosley, A. R., Fathman, J. W., Dimov, I. K., Seita, J., & Weissman, I. L. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.02.001 · Cited by 65 · see citing works
Schmukle, A. C., & Walczak, H. (2012) · Journal of Cell Science · doi:10.1242/jcs.091793 · Cited by 56 · see citing works
Self-citationHamaguchi, I., Morisada, T., Azuma, M., Murakami, K., Kuramitsu, M., Mizukami, T., Ohbo, K., Yamaguchi, K., Oike, Y., Dumont, D., et al. (2005) · Blood · doi:10.1182/blood-2005-05-1823 · Cited by 15 · see citing works
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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
Swatek, K. N., & Komander, D. (2016) · Cell Research · doi:10.1038/cr.2016.39 · Cited by 2,070 · see citing works
30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology
Zhang, Q., Lenardo, M. J., & Baltimore, D. (2017) · Cell · doi:10.1016/j.cell.2016.12.012 · Cited by 1,979 · see citing works
Regulation of tumour necrosis factor signalling: live or let die
Brenner, D., Blaser, H., & Mak, T. W. (2015) · Nature Reviews Immunology · doi:10.1038/nri3834 · Cited by 998 · 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
Breaking the chains: deubiquitylating enzyme specificity begets function
Clague, M. J., Urbé, S., & Komander, D. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0099-1 · Cited by 839 · see citing works
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
Wang, Y., & Kanneganti, T.-D. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.07.038 · Cited by 545 · 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
Self-citationUbiquitination in the regulation of inflammatory cell death and cancer
Cockram, P. E., Kist, M., Prakash, S., Chen, S., Wertz, I. E., & Vucic, D. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-020-00708-5 · Cited by 520 · see citing works
The deubiquitinase OTULIN is an essential negative regulator of inflammation and autoimmunity
Damgaard, R. B., Walker, J. A., Marco-Casanova, P., Morgan, N. V., Titheradge, H. L., Elliott, P. R., McHale, D., Maher, E. R., McKenzie, A. N. J., & Komander, D. (2016) · Cell · doi:10.1016/j.cell.2016.07.019 · Cited by 348 · see citing works
Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease
Lalaoui, N., Boyden, S. E., Oda, H., Wood, G., Stone, D. L., Chau, D., Liu, L., Stoffels, M., Kratina, T., Lawlor, K. E., et al. (2019) · Nature · doi:10.1038/s41586-019-1828-5 · Cited by 331 · see citing works
Self-citationWebster, J. D., & Vucic, D. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00365 · Cited by 315 · see citing works
Necroptosis molecular mechanisms: Recent findings regarding novel necroptosis regulators
Seo, J., Nam, Y., Kim, S., Oh, D., & Song, J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00634-7 · Cited by 310 · see citing works
Boisson, B., Laplantine, E., Dobbs, K., Cobat, A., Tarantino, N., Hazen, M. M., Lidov, H. G. W., Hopkins, G., Du, L., Belkadi, A., et al. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20141130 · Cited by 293 · see citing works
Dráber, P., Kupka, S., Reichert, M., Draberova, H., Lafont, É., de Miguel, D., Spilgies, L. M., Šurinová, S., Taraborrelli, L., Hartwig, T., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.11.009 · Cited by 288 · see citing works
Self-citationCheckpoints 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
TBK1 and IKKε prevent TNF-induced cell death by RIPK1 phosphorylation
Lafont, E., Draber, P., Rieser, E., Reichert, M., Kupka, S., de Miguel, D., Draberova, H., von Mässenhausen, A., Bhamra, A., Henderson, S., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0229-6 · Cited by 283 · see citing works
Self-citationZhou, Q., Yu, X., Demirkaya, E., Deuitch, N. T., Stone, D. L., Tsai, W. L., Kuehn, H. S., Wang, H., Yang, D., Park, Y. H., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612594113 · Cited by 274 · see citing works
TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice
Rickard, J. A., Anderton, H., Etemadi, N., Nachbur, U., Darding, M., Peltzer, N., Lalaoui, N., Lawlor, K. E., Vanyai, H. K., Hall, C. M., et al. (2014) · eLife · doi:10.7554/elife.03464 · Cited by 261 · see citing works
Self-citationMitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency
Giampazolias, E., Zunino, B., Dhayade, S., Bock, F., Cloix, C., Cao, K., Roca, A., Lopez, J., Ichim, G., Proïcs, E., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3596 · Cited by 258 · see citing works
Self-citationMore to Life than NF-κB in TNFR1 Signaling
Ting, A. T., & Bertrand, M. J. M. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.06.002 · Cited by 254 · see citing works
Phosphorylation and linear ubiquitin direct A20 inhibition of inflammation
Wertz, I. E., Newton, K., Seshasayee, D., Kusam, S., Lam, C., Zhang, J., Popovych, N., Helgason, E., Schoeffler, A. J., Jeet, S., et al. (2015) · Nature · doi:10.1038/nature16165 · Cited by 248 · see citing works
Intracellular regulation of TNF activity in health and disease
Varfolomeev, E. E., & Vucic, D. (2016) · Cytokine · doi:10.1016/j.cyto.2016.08.035 · Cited by 247 · see citing works
Aksentijevich, I. A., & Zhou, Q. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00399 · Cited by 212 · see citing works
LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis
Peltzer, N., Darding, M., Montinaro, A., Dráber, P., Draberova, H., Kupka, S., Rieser, E., Fisher, A. D., Hutchinson, J. C., Taraborrelli, L., et al. (2018) · Nature · doi:10.1038/s41586-018-0064-8 · Cited by 201 · see citing works
Self-citationOTULIN limits cell death and inflammation by deubiquitinating LUBAC
Heger, K., Wickliffe, K. E., Ndoja, A., Zhang, J., Murthy, A., Dugger, D. L., Maltzman, A., Melo, F. D. S. E., Hung, J., Zeng, Y., et al. (2018) · Nature · doi:10.1038/s41586-018-0256-2 · Cited by 200 · 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
Self-citationPoly-ubiquitination in TNFR1-mediated necroptosis
Dondelinger, Y., Darding, M., Bertrand, M. J. M., & Walczak, H. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2191-4 · Cited by 173 · see citing works
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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
A20 and cell death-driven inflammation
Priem, D., van Loo, G., & Bertrand, M. J. M. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.03.001 · Cited by 139 · see citing works
Ubiquitin enzymes in the regulation of immune responses
Ebner, P., Versteeg, G. A., & Ikeda, F. (2017) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2017.1325829 · Cited by 139 · see citing works
A20 at the Crossroads of Cell Death, Inflammation, and AutoimmunityPreprint
Martens, A., & Loo, G. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a036418 · Cited by 138 · see citing works
SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes
Kupka, S., De Miguel, D., Draber, P., Martino, L., Surinova, S., Rittinger, K., & Walczak, H. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.07.086 · Cited by 135 · see citing works
Self-citationLinear ubiquitination in immunity
Shimizu, Y., Taraborrelli, L., & Walczak, H. (2015) · Immunological Reviews · doi:10.1111/imr.12309 · Cited by 135 · see citing works
Self-citationThe regulation of necroptosis by post-translational modifications
Meng, Y., Sandow, J. J., Czabotar, P. E., & Murphy, J. M. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-020-00722-7 · Cited by 127 · see citing works
The Met1-Linked Ubiquitin Machinery: Emerging Themes of (De)regulation
Hrdinka, M., & Gyrd‐Hansen, M. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.09.001 · Cited by 118 · see citing works
Damgaard, R. B., Elliott, P. R., Swatek, K. N., Maher, E. R., Stepensky, P., Elpeleg, O. N., Komander, D., & Berkun, Y. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201809324 · Cited by 117 · see citing works
The ubiquitin system: a critical regulator of innate immunity and pathogen–host interactions
Li, J., Chai, Q., & Liu, C. H. (2016) · Cellular and Molecular Immunology · doi:10.1038/cmi.2016.40 · Cited by 115 · see citing works
The linear ubiquitin chain assembly complex regulates TRAIL‐induced gene activation and cell death
Lafont, E., Kantari‐Mimoun, C., Draber, P., De Miguel, D., Hartwig, T., Reichert, M., Kupka, S., Shimizu, Y., Taraborrelli, L., Spit, M., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201695699 · Cited by 114 · see citing works
Self-citationCellular IAP proteins and LUBAC differentially regulate necrosome-associated RIP1 ubiquitination
de Almagro, M. C., Goncharov, T., Newton, K., & Vucic, D. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.158 · Cited by 114 · see citing works
Regulation of the linear ubiquitination of STAT1 controls antiviral interferon signaling
Zuo, Y., Feng, Q., Jin, L., Huang, F., Miao, Y., Liu, J., Xu, Y., Chen, X., Zhang, H., Guo, T., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14948-z · Cited by 114 · see citing works
Roles of linear ubiquitinylation, a crucial regulator of NF ‐κB and cell death, in the immune system
Sasaki, K., & Iwaï, K. (2015) · Immunological Reviews · doi:10.1111/imr.12308 · Cited by 110 · see citing works
SPATA2 promotes CYLD activity and regulates TNF‐induced NF‐κB signaling and cell death
Schlicher, L., Wissler, M., Preiss, F., Brauns‐Schubert, P., Jakob, C., Dumit, V. I., Borner, C., Dengjel, J., & Maurer, U. (2016) · EMBO Reports · doi:10.15252/embr.201642592 · Cited by 110 · see citing works
Cell Death and Inflammation – A Vital but Dangerous Liaison
Peltzer, N., & Walczak, H. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.03.006 · Cited by 107 · see citing works
Self-citationLinear Ubiquitin Chains: Cellular Functions and Strategies for Detection and Quantification
Dittmar, G. A. G., & Winklhofer, K. F. (2020) · Frontiers in Chemistry · doi:10.3389/fchem.2019.00915 · Cited by 106 · see citing works
Multitasking Kinase RIPK1 Regulates Cell Death and InflammationPreprint
Newton, K. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a036368 · Cited by 106 · see citing works
Decoding immunogenic cell death from a dendritic cell perspective
Janssens, S., Rennen, S., & Agostinis, P. (2023) · Immunological Reviews · doi:10.1111/imr.13301 · Cited by 101 · 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
Self-citationHe, R., Liu, Y., Fu, W., He, X., Liu, S., Xiao, D., & Tao, Y. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02172-y · Cited by 99 · see citing works
Linear ubiquitin chains: enzymes, mechanisms and biology
Rittinger, K., & Ikeda, F. (2017) · Open Biology · doi:10.1098/rsob.170026 · Cited by 97 · see citing works
Tang, Y., Tu, H., Zhang, J., Zhao, X., Wang, Y., Qin, J., & Lin, X. (2019) · Nature Communications · doi:10.1038/s41467-019-12033-8 · Cited by 96 · see citing works
Linear ubiquitination at a glance
Spit, M., Rieser, E., & Walczak, H. (2019) · Journal of Cell Science · doi:10.1242/jcs.208512 · Cited by 94 · see citing works
Self-citationFujita, H., Tokunaga, A., Shimizu, S., Whiting, A. L., Aguilar-Alonso, F. A., Takagi, K., Walinda, E., Sasaki, Y., Shimokawa, T., Mizushima, T., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.112 · Cited by 93 · see citing works
LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation
Zinngrebe, J., Rieser, E., Taraborrelli, L., Peltzer, N., Hartwig, T., Ren, H., Kovács, I., Endres, C., Dráber, P., Darding, M., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20160041 · Cited by 92 · see citing works
Self-citationThe mechanism of linear ubiquitination in regulating cell death and correlative diseases
Gao, L., Zhang, W., Shi, X. H., Chang, X., Han, Y., Liu, C., Jiang, Z., & Yang, X. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06183-3 · Cited by 86 · see citing works
Recent advances in understanding inhibitor of apoptosis proteins
Lalaoui, N., & Vaux, D. L. (2018) · F1000Research · doi:10.12688/f1000research.16439.1 · Cited by 85 · see citing works
Chu, Y., Kang, Y., Yan, C., Yang, C., Zhang, T., Huo, H., & Liu, Y. (2020) · Autophagy · doi:10.1080/15548627.2020.1781393 · Cited by 85 · see citing works
The HOIL-1L ligase modulates immune signalling and cell death via monoubiquitination of LUBAC
Fuseya, Y., Fujita, H., Kim, M., Ohtake, F., Nishide, A., Sasaki, K., Saeki, Y., Tanaka, K., Takahashi, R., & Iwaï, K. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0517-9 · Cited by 84 · see citing works
Oda, H., Beck, D. B., Kuehn, H. S., Moura, N. S., Hoffmann, P. M., Ibarra, M. F., Stoddard, J. L., Tsai, W. L., Gutierrez-Cruz, G., Gadina, M., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00479 · Cited by 83 · see citing works
An 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 · see citing works
Mechanism and disease association of E2-conjugating enzymes: lessons from UBE2T and UBE2L3
Alpi, A. F., Chaugule, V. K., & Walden, H. (2016) · Biochemical Journal · doi:10.1042/bcj20160028 · Cited by 80 · see citing works
Chen, S., Wang, C., Yeo, S. K., Liang, C.-C., Okamoto, T., Sun, S., Wen, J., & Guan, J. (2016) · Genes & Development · doi:10.1101/gad.276428.115 · Cited by 80 · see citing works
OTULIN protects the liver against cell death, inflammation, fibrosis, and cancer
Damgaard, R. B., Jolin, H. E., Allison, M., Davies, S. E., Titheradge, H. L., McKenzie, A. N. J., & Komander, D. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0532-1 · Cited by 78 · see citing works
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 76 · see citing works
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
Posttranslational Modification as a Critical Determinant of Cytoplasmic Innate Immune Recognition
Baker, P. J., Nardo, D. D., Moghaddas, F., Tran, L. S., Bachem, A., Nguyen, T. A., Hayman, T. J., Tye, H., Vince, J. E., Bedoui, S., et al. (2017) · Physiological Reviews · doi:10.1152/physrev.00026.2016 · Cited by 74 · see citing works
The Met1-linked ubiquitin machinery in inflammation and infection
Fiil, B. K., & Gyrd‐Hansen, M. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-020-00702-x · Cited by 71 · see citing works
Non-lysine ubiquitylation: Doing things differently
Kelsall, I. R. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.1008175 · Cited by 71 · see citing works
RIPK3 signaling and its role in the pathogenesis of cancers
Liu, S., Joshi, K., Denning, M. F., & Zhang, J. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03947-y · Cited by 70 · see citing works
Linear ubiquitination signals in adaptive immune responses
Ikeda, F. (2015) · Immunological Reviews · doi:10.1111/imr.12300 · Cited by 68 · see citing works
Ubiquitin Ligases cIAP1 and cIAP2 Limit Cell Death to Prevent Inflammation
Zhang, J., Webster, J. D., Dugger, D. L., Goncharov, T., Roose‐Girma, M., Hung, J., Kwon, Y. C., Vucic, D., Newton, K., & Dixit, V. M. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.111 · Cited by 67 · see citing works
Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis
Bolik, J., Krause, F., Stevanovic, M., Gandraß, M., Thomsen, I., Schacht, S.-S., Rieser, E., Müller, M., Schumacher, N., Fritsch, J., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20201039 · Cited by 66 · see citing works
Self-citationMet1-linked ubiquitin signalling in health and disease: inflammation, immunity, cancer, and beyond
Jahan, A. S., Elbæk, C. R., & Damgaard, R. B. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-020-00676-w · Cited by 64 · see citing works
Teh, C. E., Lalaoui, N., Jain, R., Policheni, A. N., Heinlein, M., Álvarez-Díaz, S., Sheridan, J. M., Rieser, E., Deuser, S., Darding, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms13353 · Cited by 64 · see citing works
Self-citationMST1 Negatively Regulates TNFα-Induced NF-κB Signaling through Modulating LUBAC Activity
Lee, I. Y., Lim, J. M., Cho, H., Kim, E., Kim, Y., Oh, H.-K., Yang, W. S., Roh, K.-H., Park, H. W., Mo, J., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.022 · Cited by 64 · see citing works
OTULIN in NF-κB signaling, cell death, and disease
Verboom, L., Hoste, E., & Loo, G. (2021) · Trends in Immunology · doi:10.1016/j.it.2021.05.003 · Cited by 60 · see citing works
Vasculitis in Systemic Autoinflammatory Diseases
Demir, S., Sağ, E., Dedeoğlu, F., & Özen, S. (2018) · Frontiers in Pediatrics · doi:10.3389/fped.2018.00377 · Cited by 59 · see citing works
The multifaceted role of the E3 ubiquitin ligase HOIL ‐1: beyond linear ubiquitination
Elton, L., Carpentier, I., Verhelst, K., Staal, J., & Beyaert, R. (2015) · Immunological Reviews · doi:10.1111/imr.12307 · Cited by 59 · see citing works
Roles of ubiquitin in autophagy and cell death
Diaz, C. G., & Ikeda, F. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.09.004 · Cited by 58 · see citing works
The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains
Carvajal, A. R., Grishkovskaya, I., Diaz, C. G., Vogel, A., Sonn-Segev, A., Kushwah, M. S., Schodl, K., Deszcz, L., Orbán-Németh, Z., Sakamoto, S., et al. (2021) · eLife · doi:10.7554/elife.60660 · Cited by 57 · see citing works
Verboom, L., Martens, A., Priem, D., Hoste, E., Sze, M., Vikkula, H., Hove, L. V., Voet, S., Roels, J., Maelfait, J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.028 · Cited by 56 · see citing works
Ju, E., Park, K. A., Shen, H., & Hur, G. M. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00847-4 · Cited by 54 · see citing works
OTULIN inhibits RIPK1-mediated keratinocyte necroptosis to prevent skin inflammation in mice
Schünke, H., Göbel, U., Đikić, I., & Pasparakis, M. (2021) · Nature Communications · doi:10.1038/s41467-021-25945-1 · Cited by 53 · see citing works
HOIP modulates the stability of GPx4 by linear ubiquitination
Dong, K., Wei, R., Jin, T., Zhang, M., Shen, J., Xiang, H., Shan, B., Yuan, J., & Li, Y. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2214227119 · Cited by 52 · see citing works
Vringer, E., Heilig, R., Riley, J. S., Black, A. R. S., Cloix, C., Skalka, G., Montes-Gómez, A. E., Aguado, A., Lilla, S., Walczak, H., et al. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00044-1 · Cited by 52 · see citing works
Self-citationMolecular bases for HOIPINs-mediated inhibition of LUBAC and innate immune responses
Oikawa, D., Sato, Y., Ohtake, F., Komakura, K., Hanada, K., Sugawara, K., Terawaki, S., Mizukami, Y., Hoang, P. T., Iio, K., et al. (2020) · Communications Biology · doi:10.1038/s42003-020-0882-8 · Cited by 52 · see citing works
Structural Insights into SHARPIN-Mediated Activation of HOIP for the Linear Ubiquitin Chain Assembly
Liu, J., Wang, Y., Gong, Y., Fu, T., Hu, S., Zhou, Z., & Pan, L. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.031 · Cited by 50 · 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
RBCK1 promotes p53 degradation via ubiquitination in renal cell carcinoma
Yu, S., Dai, J., Ma, M., Xu, T., Kong, Y., Cui, C., Chi, Z., Si, L., Tang, H., Yang, L., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1488-2 · Cited by 49 · see citing works
Post-translational Modification of OTULIN Regulates Ubiquitin Dynamics and Cell Death
Douglas, T., & Saleh, M. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.11.014 · Cited by 49 · see citing works
Zhang, H., Zhao, X., Guo, Y., Chen, R., He, J., Li, L., Qiang, Z., Yang, Q., Liu, X., Huang, C., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25739-5 · Cited by 49 · see citing works
Linear ubiquitination by LUBEL has a role in Drosophila heat stress response
Asaoka, T., Almagro, J., Ehrhardt, C., Tsai, Y. I., Schleiffer, A., Deszcz, L., Junttila, S., Ringrose, L., Mechtler, K., Kavirayani, A. M., et al. (2016) · EMBO Reports · doi:10.15252/embr.201642378 · Cited by 48 · see citing works
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 47 · see citing works
The roles of ubiquitination in extrinsic cell death pathways and its implications for therapeutics
Seo, J., Kim, M. W., Bae, K., Lee, S. C., Song, J., & Lee, E. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.11.012 · Cited by 47 · see citing works
TNF receptor signalling in autoinflammatory diseases
Jarosz-Griffiths, H., Holbrook, J. A., Reyna, S. J. L., & McDermott, M. (2019) · International Immunology · doi:10.1093/intimm/dxz024 · Cited by 46 · see citing works
Innate and adaptive immune abnormalities underlying autoimmune diseases: the genetic connections
Chi, X., Huang, M., Tu, H., Zhang, B., Lin, X., Xu, H., Dong, C., & Hu, X. (2023) · Science China Life Sciences · doi:10.1007/s11427-021-2187-3 · Cited by 45 · see citing works
Silke, J., & Vince, J. E. (2016) · Current topics in microbiology and immunology · doi:10.1007/82_2016_507 · Cited by 45 · see citing works
Self-citationPaving TRAIL’s Path with Ubiquitin
Lafont, É., Hartwig, T., & Walczak, H. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.11.002 · Cited by 45 · see citing works
Self-citation
- Authors
- Peltzer, N., Rieser, E., Taraborrelli, L., Draber, P., Darding, M., Pernaute, B., Shimizu, Y., Sarr, A., Draberova, H., Montinaro, A., Martinez-Barbera, J. P., Silke, J., Rodriguez, T. A., & Walczak, H.
- Affiliations
- University College London (GB)
- The University of Melbourne (AU)
- Corresponding author
- Walczak, Henning
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 9
- Issue
- 1
- Pages
- 153-165
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2090903823
- Cited by
- 257
- References
- 54
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 22 · 2023: 27 · 2022: 19 · 2021: 42 · 2020: 19 · 2019: 22 · 2018: 20 · 2017: 20 · 2016: 27 · 2015: 13 · 2014: 2
- FWCI
- 6.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Science Foundation
- Wellcome Trust (/Z/11/Z, 096831/Z/11/A, 096831, 096831/Z/11/Z)
- Imperial College London
- National Heart and Lung Institute
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (148447)
- Genentech
- Medical Research Council (MR/K00090X/1)
- National Health and Medical Research Council (602516)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- HOIP, LUBAC, linear ubiquitination, endothelial cell death, TNFR1, TNF-α, lymphotoxin, embryonic lethality, vascularization, complex II, ubiquitin ligase, endothelial integrity, embryonic development
- MeSH terms
- Animals, Embryo, Mammalian, Female, Lymphotoxin-alpha, Male, Mice, Inbred C57BL, Mice, Transgenic, Tumor Necrosis Factor-alpha, Yolk Sac, NF-kappa B, Cell Death, Apoptosis, Mice, Knockout, Mitogen-Activated Protein Kinases, Embryo Loss, Ubiquitin, Endothelial Cells, Ubiquitin-Protein Ligases, Receptors, Tumor Necrosis Factor, Type I, Mice, Ubiquitination
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