SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex
Abstract
Cpdm (chronic proliferative dermatitis) mice develop chronic dermatitis and an immunodeficiency with increased serum IgM, symptoms that resemble those of patients with X-linked hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED), which is caused by mutations in NEMO (NF-κB essential modulator; also known as IKBKG). Spontaneous null mutations in the Sharpin (SHANK-associated RH domain interacting protein in postsynaptic density) gene are responsible for the cpdm phenotype in mice. SHARPIN shows significant similarity to HOIL-1L (also known as RBCK1), a component of linear ubiquitin chain assembly complex (LUBAC), which induces NF-κB activation through conjugation of linear polyubiquitin chains to NEMO. Here, we identify SHARPIN as an additional component of LUBAC. SHARPIN-containing complexes can linearly ubiquitinate NEMO and activated NF-κB. Thus, we re-define LUBAC as a complex containing SHARPIN, HOIL-1L, and HOIP (also known as RNF31). Deletion of SHARPIN drastically reduced the amount of LUBAC, which resulted in attenuated TNF-α- and CD40-mediated activation of NF-κB in mouse embryonic fibroblasts (MEFs) or B cells from cpdm mice. Considering the pleomorphic phenotype of cpdm mice, these results confirm the predicted role of LUBAC-mediated linear polyubiquitination in NF-κB activation induced by various stimuli, and strongly suggest the involvement of LUBAC-induced NF-κB activation in various disorders.
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SHARPIN interacts with RBCK1 (HOIL) and RNF31 (HOIP) to form LUBAC, a regulator of canonical NF-kB pathway signalling.
“The most explored function of SHARPIN is its interaction with RBCK1 (HOIL) and RNF31 (HOIP) to form the Linear Ubiquitination Assembly Complex (LUBAC), a regulator of the canonical NF- κB pathway signalling”
From SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis (2022) · cites this paper as Tokunaga, Nakagawa et al., 2011
Cites
Shared Principles in NF-κB Signaling
Hayden, M. S., & Ghosh, S. (2008) · Cell · doi:10.1016/j.cell.2008.01.020 · Cited by 4,814 · see citing works
Nuclear factor-κB in cancer development and progression
Karin, M. (2006) · Nature · doi:10.1038/nature04870 · Cited by 3,519 · see citing works
Regulation and Function of NF-κB Transcription Factors in the Immune System
Vallabhapurapu, S., & Karin, M. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132641 · Cited by 2,578 · see citing works
Yamaoka, S., Courtois, G., Chable-Bessia, C., Whiteside, S. T., Weil, R., Agou, F., Kirk, H., Kay, R. J., & Israël, A. (1998) · Cell · doi:10.1016/s0092-8674(00)81466-x · Cited by 1,077 · 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
Self-citationA ubiquitin ligase complex assembles linear polyubiquitin chains
Kirisako, T., Kamei, K., Murata, S., Kato, M., Fukumoto, H., Kanie, M., Sano, S., Tokunaga, F., Tanaka, K., & Iwaï, K. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601360 · Cited by 772 · see citing works
Self-citationHaas, 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
Ubiquitylation in innate and adaptive immunity
Bhoj, V. G., & Chen, Z. J. (2009) · Nature · doi:10.1038/nature07959 · Cited by 632 · see citing works
Koni, P. A., Sacca, R. E., Lawton, P., Browning, J. L., Ruddle, N. H., & Flavell, R. A. (1997) · Immunity · doi:10.1016/s1074-7613(00)80292-7 · Cited by 589 · see citing works
Zonana, J., Elder, M. E., Schneider, L. C., Orlow, S. J., Moss, C., Golabi, M., Shapira, S. K., Farndon, P. A., Wara, D. W., Emmal, S. A., et al. (2000) · The American Journal of Human Genetics · doi:10.1086/316914 · Cited by 521 · see citing works
Iwai, K., Yamanaka, K., Kamura, T., Minato, N., Conaway, R. C., Conaway, J. W., Klausner, R. D., & Pause, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.22.12436 · Cited by 508 · see citing works
Jain, A., Ma, C. A., Liu, S., Brown, M. R., Cohen, J., & Strober, W. (2001) · Nature Immunology · doi:10.1038/85277 · Cited by 385 · see citing works
Gerondakis, S., Grumont, R. J., Gugasyan, R., Wong, W. W.-L., Isomura, I., Ho, W. C., & Banerjee, A. (2006) · Oncogene · doi:10.1038/sj.onc.1209944 · Cited by 304 · see citing works
Smahi, A. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.20.2371 · Cited by 294 · see citing works
Xu, M., Skaug, B. A., Zeng, W., & Chen, Z. J. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.10.002 · Cited by 246 · see citing works
Linear polyubiquitination: a new regulator of NF‐κB activation
Iwaï, K., & Tokunaga, F. (2009) · EMBO Reports · doi:10.1038/embor.2009.144 · Cited by 214 · 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
Identification of the ubiquitin–protein ligase that recognizes oxidized IRP2
Yamanaka, K., Ishikawa, H., Megumi, Y., Tokunaga, F., Kanie, M., Rouault, T. A., Morishima, I., Minato, N., Ishimori, K., & Iwai, K. (2003) · Nature Cell Biology · doi:10.1038/ncb952 · Cited by 181 · see citing works
Self-citationLim, S., Sala, C., Yoon, J., Park, S., Kuroda, S., Sheng, M., & Kim, E. (2001) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2000.0940 · Cited by 151 · see citing works
Specific NEMO mutations impair CD40-mediated c-Rel activation and B cell terminal differentiation
Jain, A., Ma, C. A., López‐Granados, E., Means, G., Brady, W., Orange, J. S., Liu, S., Holland, S. M., & Derry, J. M. J. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21345 · Cited by 90 · see citing works
HogenEsch, H., Janke, S., Boggess, D., & Sundberg, J. P. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.7.3890 · Cited by 64 · see citing works
Newly identified tumor-associated role of human Sharpin
Jung, J., Kim, J. M., Park, B., Cheon, Y., Lee, B., Choo, S. H., Koh, S. S., & Lee, S. (2010) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-010-0413-x · Cited by 59 · see citing works
Abnormal Lymphoid Organ Development in Immunodeficient Mutant Mice
Seymour, R. E., Sundberg, J. P., & Esch, H. H. (2006) · Veterinary Pathology · doi:10.1354/vp.43-4-401 · Cited by 52 · see citing works
Renninger, M. L., Seymour, R. E., Whiteley, L. O., Sundberg, J. P., & HogenEsch, H. (2009) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.00944.x · Cited by 30 · see citing works
Piao, J., Yoshida, H., Yeh, W., Doi, T., Xue, X., Yagita∥, H., Okumura, K., & Nakano, H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.4.2272 · Cited by 15 · see citing works
Self-citationTorres, G., Gijbels, M. J., HogenEsch, H., & Kraal, G. (2008) · Pathobiology · doi:10.1159/000163970 · Cited by 13 · see citing works
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Komander, D., & Rape, M. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060310-170328 · Cited by 3,679 · see citing works
Swatek, K. N., & Komander, D. (2016) · Cell Research · doi:10.1038/cr.2016.39 · Cited by 2,070 · see citing works
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 · see citing works
NF-κB, the first quarter-century: remarkable progress and outstanding questions
Hayden, M. S., & Ghosh, S. (2012) · Genes & Development · doi:10.1101/gad.183434.111 · Cited by 1,693 · see citing works
Signaling in innate immunity and inflammation
Newton, K., & Dixit, V. M. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a006049 · Cited by 1,513 · see citing works
Ubiquitin ligases: structure, function, and regulation
Zheng, N., & Shabek, N. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014922 · Cited by 1,499 · see citing works
TNF biology, pathogenic mechanisms and emerging therapeutic strategies
Kalliolias, G. D., & Ivashkiv, L. B. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.169 · Cited by 1,390 · see citing works
Regulation of NF-κB by TNF family cytokines
Hayden, M. S., & Ghosh, S. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.05.004 · Cited by 1,116 · see citing works
The increasing complexity of the ubiquitin code
Yau, R., & Rape, M. (2016) · Nature Cell Biology · doi:10.1038/ncb3358 · Cited by 1,054 · 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
Deubiquitylating enzymes and drug discovery: emerging opportunities
Harrigan, J. A., Jacq, X., Martin, N. M., & Jackson, S. P. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.152 · Cited by 940 · 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
Wagner, S., Beli, P., Weinert, B. T., Nielsen, M. L., Cox, J., Mann, M., & Choudhary, C. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.013284 · Cited by 889 · see citing works
Targeting IAP proteins for therapeutic intervention in cancer
Fulda, S., & Vucic, D. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3627 · Cited by 837 · see citing works
Sedger, L. M., & McDermott, M. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.07.016 · Cited by 774 · see citing works
Ubiquitin-Binding Proteins: Decoders of Ubiquitin-Mediated Cellular Functions
Husnjak, K., & Đikić, I. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-051810-094654 · Cited by 755 · see citing works
Malireddi, R. K. S., Kesavardhana, S., & Kanneganti, T. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00406 · Cited by 750 · see citing works
The role of ubiquitination in tumorigenesis and targeted drug discovery
Deng, L., Meng, T., Chen, L., Wei, W., & Wang, P. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0107-0 · Cited by 744 · see citing works
Atypical ubiquitylation — the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages
Kulathu, Y., & Komander, D. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3394 · Cited by 642 · see citing works
NF-κB: At the Borders of Autoimmunity and Inflammation
Barnabei, L., Laplantine, E., Mbongo, W., Rieux‐Laucat, F., & Weil, R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.716469 · Cited by 641 · see citing works
Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death
Ofengeim, D., & Yuan, J. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3683 · Cited by 615 · see citing works
The IκB kinase complex in NF‐κB regulation and beyond
Hinz, M., & Scheidereit, C. (2014) · The EMBO Reports · doi:10.1002/embr.201337983 · Cited by 572 · see citing works
Decoding Toll-like receptors: Recent insights and perspectives in innate immunity
Kawai, T., Ikegawa, M., Ori, D., & Akira, S. (2024) · Immunity · doi:10.1016/j.immuni.2024.03.004 · Cited by 554 · see citing works
Integrin activation by talin, kindlin and mechanical forces
Sun, Z., Costell, M., & Fässler, R. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0234-9 · Cited by 545 · see citing works
Ubiquitination 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
Chu, W. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.10.014 · Cited by 503 · see citing works
The TNF Family of Ligands and Receptors: Communication Modules in the Immune System and Beyond
Dostert, C., Grusdat, M., Letellier, E., & Brenner, D. (2018) · Physiological Reviews · doi:10.1152/physrev.00045.2017 · Cited by 502 · see citing works
OTULIN Antagonizes LUBAC Signaling by Specifically Hydrolyzing Met1-Linked Polyubiquitin
Keusekotten, K., Elliott, P. R., Glockner, L., Fiil, B. K., Damgaard, R. B., Kulathu, Y., Wauer, T., Hospenthal, M. K., Gyrd‐Hansen, M., Krappmann, D., et al. (2013) · Cell · doi:10.1016/j.cell.2013.05.014 · Cited by 489 · see citing works
Boisson, B., Laplantine, E., Prando, C., Giliani, S. C., Israelsson, E., Xu, Z., Abhyankar, A., Israël, L., Trevejo-Nuñez, G., Bogunovic, D., et al. (2012) · Nature Immunology · doi:10.1038/ni.2457 · Cited by 470 · see citing works
Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death
Vucic, D., Dixit, V. M., & Wertz, I. E. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3143 · Cited by 451 · 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
Ubiquitination in signaling to and activation of IKK
Chen, Z. J. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01108.x · Cited by 419 · see citing works
Newton, K., & Manning, G. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014830 · Cited by 401 · see citing works
Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · 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
The spatial and temporal organization of ubiquitin networks
Grabbe, C., Husnjak, K., & Đikić, I. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3099 · Cited by 368 · see citing works
Programmed Necrosis in the Cross Talk of Cell Death and Inflammation
Chan, F. K.-M., Luz, N. F., & Moriwaki, K. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112248 · Cited by 350 · see citing works
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
Inhibitor of Apoptosis (IAP) Proteins-Modulators of Cell Death and InflammationPreprint
Silke, J., & Meier, P. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008730 · Cited by 329 · see citing works
Function and regulation of IL ‐1α in inflammatory diseases and cancer
Malik, A., & Kanneganti, T. (2017) · Immunological Reviews · doi:10.1111/imr.12615 · Cited by 325 · see citing works
Webster, J. D., & Vucic, D. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00365 · Cited by 315 · see citing works
RBR E3 ubiquitin ligases: new structures, new insights, new questions
Spratt, D. E., Walden, H., & Shaw, G. S. (2014) · Biochemical Journal · doi:10.1042/bj20140006 · Cited by 314 · 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
Iwasaki, H., Takeuchi, O., Teraguchi, S., Matsushita, K., Uehata, T., Kuniyoshi, K., Satoh, T., Saitoh, T., Matsushita, M., Standley, D. M., et al. (2011) · Nature Immunology · doi:10.1038/ni.2137 · Cited by 288 · 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
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
Zhou, 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
OTULIN Restricts Met1-Linked Ubiquitination to Control Innate Immune Signaling
Fiil, B. K., Damgaard, R. B., Wagner, S., Keusekotten, K., Fritsch, M., Bekker‐Jensen, S., Mailand, N., Choudhary, C., Komander, D., & Gyrd‐Hansen, M. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.06.004 · Cited by 265 · 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
Regulation of NF‐κB by deubiquitinases
Harhaj, E. W., & Dixit, V. M. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01100.x · Cited by 260 · see citing works
Regulation of NF-κB by ubiquitination
Chen, J., & Chen, Z. J. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.12.005 · Cited by 258 · see citing works
HOIP Deficiency Causes Embryonic Lethality by Aberrant TNFR1-Mediated Endothelial Cell Death
Peltzer, N., Rieser, E., Taraborrelli, L., Draber, P., Darding, M., Pernaute, B., Shimizu, Y., Sarr, A., Draberova, H., Montinaro, A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.066 · Cited by 257 · see citing works
DNA damage‐dependent NF‐κB activation: NEMO turns nuclear signaling inside out
McCool, K. W., & Miyamoto, S. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01101.x · Cited by 251 · 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
The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation
Rodgers, M. A., Bowman, J. W., Fujita, H., Orazio, N., Shi, M., Liang, Q., Amatya, R., Kelly, T. J., Iwai, K., Ting, J., et al. (2014) · Journal of Experimental Medicine · doi:10.1084/jem.20132486 · Cited by 247 · see citing works
Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF‐κB regulation
Tokunaga, F., Nishimasu, H., Ishitani, R., Goto, E., Noguchi, T., Mio, K., Kamei, K., Ma, A. I., Iwaï, K., & Nureki, O. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.241 · Cited by 235 · see citing works
Self-citationKlein, T., Eckhard, U., Dufour, A., Solis, N., & Overall, C. M. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00120 · Cited by 229 · 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
TNF and ubiquitin at the crossroads of gene activation, cell death, inflammation, and cancer
Walczak, H. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01066.x · Cited by 222 · see citing works
Constructing and decoding unconventional ubiquitin chains
Behrends, C., & Harper, J. W. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2066 · Cited by 223 · see citing works
The E3 Ligase Parkin Maintains Mitochondrial Integrity by Increasing Linear Ubiquitination of NEMO
Müller-Rischart, A. K., Pilsl, A., Beaudette, P., Patra, M., Hadian, K., Funke, M., Peis, R., Deinlein, A., Schweimer, C., Kuhn, P., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.036 · Cited by 210 · see citing works
LUBAC synthesizes linear ubiquitin chains via a thioester intermediate
Stieglitz, B., Morris-Davies, A. C., Koliopoulos, M. G., Christodoulou, E., & Rittinger, K. (2012) · EMBO Reports · doi:10.1038/embor.2012.105 · Cited by 220 · see citing works
Noad, J., von der Malsburg, A., Pathe, C., Michel, M. A., Komander, D., & Randow, F. (2017) · Nature Microbiology · doi:10.1038/nmicrobiol.2017.63 · Cited by 214 · see citing works
Smit, J. J., Monteferrario, D., Noordermeer, S. M., van Dijk, W. J., van der Reijden, B. A., & Sixma, T. K. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.217 · Cited by 210 · see citing works
Non-canonical ubiquitin-based signals for proteasomal degradation
Kravtsova‐Ivantsiv, Y., & Ciechanover, A. J. (2012) · Journal of Cell Science · doi:10.1242/jcs.093567 · Cited by 211 · 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
Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation
Lechtenberg, B. C., Rajput, A., Sanishvili, R., Dobaczewska, M. K., Ware, C. F., Mace, P. D., & Riedl, S. J. (2016) · Nature · doi:10.1038/nature16511 · Cited by 208 · see citing works
Verhelst, K., Carpentier, I., Kreike, M., Meloni, L., Verstrepen, L., Kensche, T., Đikić, I., & Beyaert, R. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.240 · Cited by 203 · see citing works
Structural basis for ligase-specific conjugation of linear ubiquitin chains by HOIP
Stieglitz, B., Rana, R. R., Koliopoulos, M. G., Morris-Davies, A. C., Schaeffer, V., Christodoulou, E., Howell, S. A., Brown, N. R., Đikić, I., & Rittinger, K. (2013) · Nature · doi:10.1038/nature12638 · Cited by 202 · see citing works
SHARPIN is an endogenous inhibitor of β1-integrin activation
Rantala, J. K., Pouwels, J., Pellinen, T., Veltel, S., Laasola, P., Mattila, E., Potter, C. S., Duffy, T., Sundberg, J. P., Kallioniemi, O., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2340 · Cited by 201 · see citing works
Sadowski, M. C., Suryadinata, R., Tan, A. R., Roesley, S. N. A., & Šarčević, B. (2011) · IUBMB Life · doi:10.1002/iub.589 · Cited by 193 · see citing works
Ubiquitination in the antiviral immune response
Davis-Gardner, M. E., & Gack, M. U. (2015) · Virology · doi:10.1016/j.virol.2015.02.033 · Cited by 188 · see citing works
Cysteine methylation disrupts ubiquitin-chain sensing in NF-κB activation
Zhang, L., Ding, X., Cui, J., Xu, H., Chen, J., Gong, Y., Hu, L., Zhou, Y. W., Ge, J., Lu, Q., et al. (2011) · Nature · doi:10.1038/nature10690 · Cited by 191 · see citing works
de Almagro, M. C., & Vucic, D. (2012) · PubMed · Cited by 189 · see citing works
Necroptosis in Immunity and Ischemia-Reperfusion Injury
Linkermann, A., Hackl, M. J., Kunzendorf, U., Walczak, H., Krautwald, S., & Jevnikar, A. M. (2013) · American Journal of Transplantation · doi:10.1111/ajt.12448 · Cited by 188 · see citing works
Molecular Basis and Regulation of OTULIN-LUBAC Interaction
Elliott, P. R., Nielsen, S. V., Marco‐Casanova, P., Fiil, B. K., Keusekotten, K., Mailand, N., Freund, S. M. V., Gyrd‐Hansen, M., & Komander, D. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.018 · Cited by 185 · 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
Diverse ubiquitin signaling in NF-κB activation
Iwaï, K. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.04.001 · Cited by 181 · 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
Binding of OTULIN to the PUB Domain of HOIP Controls NF-κB Signaling
Schaeffer, V., Akutsu, M., Olma, M. H., Gomes, L. C., Kawasaki, M., & Đikić, I. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.016 · Cited by 179 · see citing works
Poly-ubiquitination in TNFR1-mediated necroptosis
Dondelinger, Y., Darding, M., Bertrand, M. J. M., & Walczak, H. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2191-4 · Cited by 173 · see citing works
van Wijk, S. J. L., Fricke, F., Herhaus, L., Gupta, J., Hötte, K., Pampaloni, F., Grumati, P., Kaulich, M., Sou, Y., Komatsu, M., et al. (2017) · Nature Microbiology · doi:10.1038/nmicrobiol.2017.66 · Cited by 172 · 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
TRAF2 Sets a Threshold for Extrinsic Apoptosis by Tagging Caspase-8 with a Ubiquitin Shutoff Timer
Gonzalvez, F., Lawrence, D., Yang, B., Yee, S. F., Pitti, R. M., Marsters, S. A., Pham, V. C., Stéphan, J.-P., Lill, J. R., & Ashkenazi, A. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.031 · Cited by 163 · see citing works
Linear 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
van Wijk, S. J. L., Fiškin, E., Putyrski, M., Pampaloni, F., Hou, J., Wild, P. S., Kensche, T., Grecco, H. E., Bastiaens, P. I. H., & Đikić, I. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.06.017 · Cited by 155 · see citing works
SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling
Elliott, P. R., Leske, D., Hrdinka, M., Bagola, K., Fiil, B. K., McLaughlin, S. H., Wagstaff, J. L., Volkmar, N., Christianson, J. C., Kessler, B. M., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.08.001 · Cited by 155 · see citing works
The complexity of recognition of ubiquitinated substrates by the 26S proteasome
Ciechanover, A. J., & Stanhill, A. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.07.007 · Cited by 152 · see citing works
Kelsall, I. R., Zhang, J., Knebel, A., Arthur, J. S. C., & Cohen, P. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1905873116 · Cited by 152 · see citing works
Klein, T., Fung, S., Renner, F., Blank, M. A., Dufour, A., Kang, S., Bolger-Munro, M., Scurll, J., Priatel, J. J., Schweigler, P., et al. (2015) · Nature Communications · doi:10.1038/ncomms9777 · Cited by 151 · see citing works
Hrdinka, M., Fiil, B. K., Zucca, M., Leske, D., Bagola, K., Yabal, M., Elliott, P. R., Damgaard, R. B., Komander, D., Jost, P. J., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.02.062 · Cited by 151 · see citing works
Nakazawa, S., Oikawa, D., Ishii, R., Ayaki, T., Takahashi, H., Takeda, H., Ishitani, R., Kamei, K., Takeyoshi, I., Kawakami, H., et al. (2016) · Nature Communications · doi:10.1038/ncomms12547 · Cited by 151 · see citing works
Self-citationRIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases
Patel, S. D., Webster, J. D., Varfolomeev, E. E., Kwon, Y. C., Cheng, J. H., Zhang, J., Dugger, D. L., Wickliffe, K. E., Maltzman, A., Sujatha-Bhaskar, S., et al. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0347-0 · Cited by 151 · see citing works
Disease‐causing mutations in the XIAP BIR2 domain impair NOD2‐dependent immune signalling
Damgaard, R. B., Fiil, B. K., Speckmann, C., Yabal, M., Stadt, U. Z., Bekker‐Jensen, S., Jost, P. J., Ehl, S. R., Mailand, N., & Gyrd‐Hansen, M. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201303090 · Cited by 148 · see citing works
Smit, J. J., & Sixma, T. K. (2014) · EMBO Reports · doi:10.1002/embr.201338166 · Cited by 146 · see citing works
- Authors
- Tokunaga, F., Nakagawa, T., Nakahara, M., Saeki, Y., Taniguchi, M., Sakata, S.-I., Tanaka, K., Nakano, H., & Iwai, K.
- Affiliations
- The University of Osaka (JP)
- Tokyo Metropolitan Institute of Medical Science (JP)
- Juntendo University (JP)
- Venue
- Nature
- Published
- 2011-03
- Volume
- 471
- Issue
- 7340
- Pages
- 633-636
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2001879129
- Cited by
- 609
- References
- 26
- Citations by year
- 2026: 21 · 2025: 17 · 2024: 30 · 2023: 22 · 2022: 41 · 2021: 57 · 2020: 35 · 2019: 38 · 2018: 39 · 2017: 43 · 2016: 46 · 2015: 42 · 2014: 46 · 2013: 42 · 2012: 57
- FWCI
- 19.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (23659404, 21000012, 23657075)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- SHARPIN, LUBAC, NF-κB activation, HOIL-1, HOIP, TNF signaling, CD40 ligand, ubiquitin conjugation, X-linked hyper-IgM syndrome, NEMO, immunodeficiency
- MeSH terms
- Animals, Carrier Proteins, Cells, Cultured, Humans, Nerve Tissue Proteins, Tumor Necrosis Factor-alpha, NF-kappa B, CD40 Ligand, Ubiquitin, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Multiprotein Complexes, Intracellular Signaling Peptides and Proteins, Mice, HEK293 Cells
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