Abstract
The signaling networks that control the immune system are coordinated by a myriad of interconnecting phosphorylation and ubiquitylation events. This review provides an overview of mutations in human genes encoding these proteins that give rise to immune diseases. Analysis of the biological effects of these mutations has revealed the true physiological roles of particular signaling networks and promises to revolutionize the treatment of these diseases.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Husnjak, K. & Dikic, I. Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu. Rev. Biochem. 81, 291–322 (2012).
Smith, H. et al. Identification of the phosphorylation sites on the E3 ubiquitin ligase Pellino that are critical for activation by IRAK1 and IRAK4. Proc. Natl. Acad. Sci. USA 106, 4584–4590 (2009).
Strack, P. et al. SCFβ-TRCP and phosphorylation dependent ubiquitination of IκBα catalyzed by Ubc3 and Ubc4. Oncogene 19, 3529–3536 (2000).
Xia, Z.P. et al. Direct activation of protein kinases by unanchored polyubiquitin chains. Nature 461, 114–119 (2009).
Cohen, P. & Alessi, D.R. Kinase drug discovery–what's next in the field? ACS Chem. Biol. 8, 96–104 (2013).
Cohen, P. & Tcherpakov, M. Will the ubiquitin system furnish as many drug targets as protein kinases? Cell 143, 686–693 (2010).
Emmerich, C.H. et al. Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains. Proc. Natl. Acad. Sci. USA 110, 15247–15252 (2013).
Fiil, B.K. et al. OTULIN restricts Met1-linked ubiquitination to control innate immune signaling. Mol. Cell 50, 818–830 (2013).
Clark, K., Nanda, S. & Cohen, P. Molecular control of the NEMO family of ubiquitin-binding proteins. Nat. Rev. Mol. Cell Biol. 14, 673–685 (2013).
Courtois, G. & Israel, A. IKK regulation and human genetics. Curr. Top. Microbiol. Immunol. 349, 73–95 (2011).
Döffinger, R. et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-κB signaling. Nat. Genet. 27, 277–285 (2001).
Ea, C.K., Deng, L., Xia, Z.P., Pineda, G. & Chen, Z.J. Activation of IKK by TNFα requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol. Cell 22, 245–257 (2006).
Wu, C.-J., Conze, D.B., Li, T., Srinivasula, S.M. & Ashwell, J.D. Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-κB activation. Nat. Cell Biol. 8, 398–406 (2006).
Kensche, T. et al. Analysis of nuclear factor-κB (NF-κB) essential modulator (NEMO) binding to linear and lysine-linked ubiquitin chains and its role in the activation of NF-κB. J. Biol. Chem. 287, 23626–23634 (2012).
Lo, Y.C. et al. Structural basis for recognition of diubiquitins by NEMO. Mol. Cell 33, 602–615 (2009).
Picard, C., Casanova, J.L. & Puel, A. Infectious diseases in patients with IRAK-4, MyD88, NEMO, or IκBα deficiency. Clin. Microbiol. Rev. 24, 490–497 (2011).
Kirisako, T. et al. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J. 25, 4877–4887 (2006).
Boisson, B. et al. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat. Immunol. 13, 1178–1186 (2012).
HogenEsch, H., Janke, S., Boggess, D. & Sundberg, J.P. Absence of Peyer's patches and abnormal lymphoid architecture in chronic proliferative dermatitis (cpdm/cpdm) mice. J. Immunol. 162, 3890–3896 (1999).
Gerlach, B. et al. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature 471, 591–596 (2011).
Ikeda, F. et al. SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis. Nature 471, 637–641 (2011).
Rigaud, S. et al. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature 444, 110–114 (2006).
Damgaard, R.B. et al. The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol. Cell 46, 746–758 (2012).
Damgaard, R.B. et al. Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling. EMBO Mol. Med. 5, 1278–1295 (2013).
Philpott, D.J., Sorbara, M.T., Robertson, S.J., Croitoru, K. & Girardin, S.E. NOD proteins: regulators of inflammation in health and disease. Nat. Rev. Immunol. 14, 9–23 (2014).
Schwandner, R., Yamaguchi, K. & Cao, Z. Requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in interleukin 17 signal transduction. J. Exp. Med. 191, 1233–1240 (2000).
Liu, C. et al. Act1, a U-box E3 ubiquitin ligase for IL-17 signaling. Sci. Signal. 2, ra63 (2009).
Qian, Y. et al. The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat. Immunol. 8, 247–256 (2007).
Boisson, B. et al. An ACT1 mutation selectively abolishes interleukin-17 responses in humans with chronic mucocutaneous candidiasis. Immunity 39, 676–686 (2013).
Conti, H.R. et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J. Exp. Med. 206, 299–311 (2009).
Iwakura, Y. & Ishigame, H. The IL-23/IL-17 axis in inflammation. J. Clin. Invest. 116, 1218–1222 (2006).
Park, H. et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6, 1133–1141 (2005).
Gleason, C.E., Ordureau, A., Gourlay, R., Arthur, J.S. & Cohen, P. Polyubiquitin binding to optineurin is required for optimal activation of TANK-binding kinase 1 and production of interferon β. J. Biol. Chem. 286, 35663–35674 (2011).
Wild, P. et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 333, 228–233 (2011).
Morton, S., Hesson, L., Peggie, M. & Cohen, P. Enhanced binding of TBK1 by an optineurin mutant that causes a familial form of primary open angle glaucoma. FEBS Lett. 582, 997–1002 (2008).
Munitic, I. et al. Optineurin insufficiency impairs IRF3 but not NF-κB activation in immune cells. J. Immunol. 191, 6231–6240 (2013).
Pilli, M. et al. TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation. Immunity 37, 223–234 (2012).
Albagha, O.M. et al. Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone. Nat. Genet. 42, 520–524 (2010).
Laurin, N., Brown, J.P., Morissette, J. & Raymond, V. Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone. Am. J. Hum. Genet. 70, 1582–1588 (2002).
Maruyama, H. et al. Mutations of optineurin in amyotrophic lateral sclerosis. Nature 465, 223–226 (2010).
Rubino, E. et al. SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Neurology 79, 1556–1562 (2012).
Rezaie, T. et al. Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science 295, 1077–1079 (2002).
Kawase, K. et al. Confirmation of TBK1 duplication in normal tension glaucoma. Exp. Eye Res. 96, 178–180 (2012).
Nanda, S.K. et al. Polyubiquitin binding to ABIN1 is required to prevent autoimmunity. J. Exp. Med. 208, 1215–1228 (2011).
Gregersen, P.K. et al. Risk for myasthenia gravis maps to a (151) Pro→Ala change in TNIP1 and to human leukocyte antigen-B*08. Ann. Neurol. 72, 927–935 (2012).
Han, J.W. et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat. Genet. 41, 1234–1237 (2009).
He, C.F. et al. TNIP1, SLC15A4, ETS1, RasGRP3 and IKZF1 are associated with clinical features of systemic lupus erythematosus in a Chinese Han population. Lupus 19, 1181–1186 (2010).
Nair, R.P. et al. Psoriasis bench to bedside: genetics meets immunology. Arch. Dermatol. 145, 462–464 (2009).
Yang, Q. et al. Investigation of 20 non-HLA (human leucocyte antigen) psoriasis susceptibility loci in Chinese patients with psoriatic arthritis and psoriasis vulgaris. Br. J. Dermatol. 168, 1060–1065 (2013).
Caster, D.J. et al. ABIN1 dysfunction as a genetic basis for lupus nephritis. J. Am. Soc. Nephrol. 24, 1743–1754 (2013).
Matmati, M. et al. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. Nat. Genet. 43, 908–912 (2011).
Skaug, B. et al. Direct, noncatalytic mechanism of IKK inhibition by A20. Mol. Cell 44, 559–571 (2011).
Tokunaga, F. et al. Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-κB regulation. EMBO J. 31, 3856–3870 (2012).
Verhelst, K. et al. A20 inhibits LUBAC-mediated NF-κB activation by binding linear polyubiquitin chains via its zinc finger 7. EMBO J. 31, 3845–3855 (2012).
Ngo, V.N. et al. Oncogenically active MYD88 mutations in human lymphoma. Nature 470, 115–119 (2011).
Nocturne, G. et al. Germline and somatic genetic variations of TNFAIP3 in lymphoma complicating primary Sjogren's syndrome. Blood 122, 4068–4076 (2013).
Dong, G. et al. A20, ABIN-1/2, and CARD11 mutations and their prognostic value in gastrointestinal diffuse large B-cell lymphoma. Clin. Cancer Res. 17, 1440–1451 (2011).
Wertz, I.E. et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling. Nature 430, 694–699 (2004).
Komander, D. et al. Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. EMBO Rep. 10, 466–473 (2009).
Lu, T.T. et al. Dimerization and ubiquitin mediated recruitment of A20, a complex deubiquitinating enzyme. Immunity 38, 896–905 (2013).
Haglund, K. & Dikic, I. The role of ubiquitylation in receptor endocytosis and endosomal sorting. J. Cell Sci. 125, 265–275 (2012).
Katoh, Y. et al. Tollip and Tom1 form a complex and recruit ubiquitin-conjugated proteins onto early endosomes. J. Biol. Chem. 279, 24435–24443 (2004).
Burns, K. et al. Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nat. Cell Biol. 2, 346–351 (2000).
Zhang, G. & Ghosh, S. Negative regulation of toll-like receptor-mediated signaling by Tollip. J. Biol. Chem. 277, 7059–7065 (2002).
Brissoni, B. et al. Intracellular trafficking of interleukin-1 receptor I requires Tollip. Curr. Biol. 16, 2265–2270 (2006).
Bulut, Y., Faure, E., Thomas, L., Equils, O. & Arditi, M. Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling. J. Immunol. 167, 987–994 (2001).
Didierlaurent, A. et al. Tollip regulates proinflammatory responses to interleukin-1 and lipopolysaccharide. Mol. Cell. Biol. 26, 735–742 (2006).
Shah, J.A. et al. Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis. J. Immunol. 189, 1737–1746 (2012).
Mira, M.T. et al. Susceptibility to leprosy is associated with PARK2 and PACRG. Nature 427, 636–640 (2004).
de Leseleuc, L. et al. PARK2 mediates interleukin 6 and monocyte chemoattractant protein 1 production by human macrophages. PLoS Negl. Trop. Dis. 7, e2015 (2013).
Hasan, Z. et al. Elevated serum CCL2 concomitant with a reduced mycobacterium-induced response leads to disease dissemination in leprosy. Scand. J. Immunol. 63, 241–247 (2006).
Keusekotten, K. et al. OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin. Cell 153, 1312–1326 (2013).
Jin, W. et al. Deubiquitinating enzyme CYLD negatively regulates RANK signaling and osteoclastogenesis in mice. J. Clin. Invest. 118, 1858–1866 (2008).
Jin, W. et al. Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells. J. Biol. Chem. 282, 15884–15893 (2007).
Reiley, W.W. et al. Regulation of T cell development by the deubiquitinating enzyme CYLD. Nat. Immunol. 7, 411–417 (2006).
Zhang, M. et al. Regulation of IκB kinase-related kinases and antiviral responses by tumor suppressor CYLD. J. Biol. Chem. 283, 18621–18626 (2008).
Sun, S.C. CYLD: a tumor suppressor deubiquitinase regulating NF-κB activation and diverse biological processes. Cell Death Differ. 17, 25–34 (2010).
Rivkin, E. et al. The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis. Nature 498, 318–324 (2013).
Lin, S.C., Lo, Y.C. & Wu, H. Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature 465, 885–890 (2010).
Motshwene, P.G. et al. An oligomeric signaling platform formed by the Toll-like receptor signal transducers MyD88 and IRAK-4. J. Biol. Chem. 284, 25404–25411 (2009).
Picard, C. et al. Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 299, 2076–2079 (2003).
Picard, C. et al. Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine (Baltimore) 89, 403–425 (2010).
Baxter, E.J. et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365, 1054–1061 (2005).
Kralovics, R. et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N. Engl. J. Med. 352, 1779–1790 (2005).
Laurence, A., Pesu, M., Silvennoinen, O. & O'Shea, J. JAK kinases in health and disease: an update. Open Rheumatol. J. 6, 232–244 (2012).
Macchi, P. et al. Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature 377, 65–68 (1995).
Russell, S.M. et al. Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science 270, 797–800 (1995).
Rochman, Y., Spolski, R. & Leonard, W.J. New insights into the regulation of T cells by γc family cytokines. Nat. Rev. Immunol. 9, 480–490 (2009).
Minegishi, Y. et al. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity 25, 745–755 (2006).
Watford, W.T. & O'Shea, J.J. Human tyk2 kinase deficiency: another primary immunodeficiency syndrome. Immunity 25, 695–697 (2006).
Li, Z. et al. Two rare disease-associated Tyk2 variants are catalytically impaired but signaling competent. J. Immunol. 190, 2335–2344 (2013).
Eyre, S. et al. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat. Genet. 44, 1336–1340 (2012).
Conley, M.E., Mathias, D., Treadaway, J., Minegishi, Y. & Rohrer, J. Mutations in Btk in patients with presumed X-linked agammaglobulinemia. Am. J. Hum. Genet. 62, 1034–1043 (1998).
Holinski-Feder, E. et al. Mutation screening of the BTK gene in 56 families with X-linked agammaglobulinemia (XLA): 47 unique mutations without correlation to clinical course. Pediatrics 101, 276–284 (1998).
Tsukada, S. et al. Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell 72, 279–290 (1993).
Vetrie, D. et al. The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature 361, 226–233 (1993).
Fischer, A. et al. ZAP70: a master regulator of adaptive immunity. Semin. Immunopathol. 32, 107–116 (2010).
Arpaia, E., Shahar, M., Dadi, H., Cohen, A. & Roifman, C.M. Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase. Cell 76, 947–958 (1994).
Chan, A.C. et al. ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. Science 264, 1599–1601 (1994).
Picard, C. et al. Hypomorphic mutation of ZAP70 in human results in a late onset immunodeficiency and no autoimmunity. Eur. J. Immunol. 39, 1966–1976 (2009).
Sakaguchi, N. et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 426, 454–460 (2003).
Aguado, E. et al. Induction of T helper type 2 immunity by a point mutation in the LAT adaptor. Science 296, 2036–2040 (2002).
Sommers, C.L. et al. A LAT mutation that inhibits T cell development yet induces lymphoproliferation. Science 296, 2040–2043 (2002).
Sancho-Shimizu, V. et al. Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency. J. Clin. Invest. 121, 4889–4902 (2011).
Zhang, S.Y. et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science 317, 1522–1527 (2007).
Herman, M. et al. Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood. J. Exp. Med. 209, 1567–1582 (2012).
Okkenhaug, K. & Vanhaesebroeck, B. PI3K in lymphocyte development, differentiation and activation. Nat. Rev. Immunol. 3, 317–330 (2003).
Lucas, C.L. et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency. Nat. Immunol. 15, 88–97 (2014).
Angulo, I. et al. Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage. Science 342, 866–871 (2013).
Bleich, A. et al. Cdcs1 a major colitis susceptibility locus in mice; subcongenic analysis reveals genetic complexity. Inflamm. Bowel Dis. 16, 765–775 (2010).
Boulard, O., Kirchberger, S., Royston, D.J., Maloy, K.J. & Powrie, F.M. Identification of a genetic locus controlling bacteria-driven colitis and associated cancer through effects on innate inflammation. J. Exp. Med. 209, 1309–1324 (2012).
Cho, J.H. The genetics and immunopathogenesis of inflammatory bowel disease. Nat. Rev. Immunol. 8, 458–466 (2008).
Cho, J.H. et al. Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: evidence for epistasis between 1p and IBD1. Proc. Natl. Acad. Sci. USA 95, 7502–7507 (1998).
Heine, M. et al. α-kinase 1, a new component in apical protein transport. J. Biol. Chem. 280, 25637–25643 (2005).
Kay, J.G., Murray, R.Z., Pagan, J.K. & Stow, J.L. Cytokine secretion via cholesterol-rich lipid raft-associated SNAREs at the phagocytic cup. J. Biol. Chem. 281, 11949–11954 (2006).
Luo, C., Wang, K., Liu, D., Li, Y. & Zhao, Q.S. The functional roles of lipid rafts in T cell activation, immune diseases and HIV infection and prevention. Cell. Mol. Immunol. 5, 1–7 (2008).
Wang, S.J. et al. Lymphocyte α-kinase is a gout-susceptible gene involved in monosodium urate monohydrate-induced inflammatory responses. J. Mol. Med. (Berl.) 89, 1241–1251 (2011).
Pauls, E. et al. Two phases of inflammatory mediator production defined by the study of IRAK2 and IRAK1 knock-in mice. J. Immunol. 191, 2717–2730 (2013).
Uematsu, S. et al. Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-α induction. J. Exp. Med. 201, 915–923 (2005).
Barrat, F.J. et al. Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J. Exp. Med. 202, 1131–1139 (2005).
Jacob, C.O. et al. Identification of novel susceptibility genes in childhood-onset systemic lupus erythematosus using a uniquely designed candidate gene pathway platform. Arthritis Rheum. 56, 4164–4173 (2007).
Jacob, C.O. et al. Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus. Proc. Natl. Acad. Sci. USA 106, 6256–6261 (2009).
Clark, K. et al. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc. Natl. Acad. Sci. USA 109, 16986–16991 (2012).
MacKenzie, K.F. et al. PGE2 induces macrophage IL-10 production and a regulatory-like phenotype via a protein kinase A–SIK–CRTC3 pathway. J. Immunol. 190, 565–577 (2013).
Jostins, L. et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119–124 (2012).
Liu, J.Z. et al. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis. Nat. Genet. 45, 670–675 (2013).
Graham, R.R. et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus (SLE). Nat. Genet. 40, 1059–1061 (2008).
Musone, S.L. et al. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat. Genet. 40, 1062–1064 (2008).
Acknowledgements
I thank S. Nanda, C. Emmerich and K. Clark for suggestions and A. Nicoll for assistance in preparing the manuscript. Supported by a Wellcome Trust Senior Investigator award (WT100294), the UK Medical Research Council (MRC_MR/K000985/1), AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Janssen Pharmaceuticals, Merck-Serono and Pfizer.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The author declares no competing financial interests.
Rights and permissions
About this article
Cite this article
Cohen, P. Immune diseases caused by mutations in kinases and components of the ubiquitin system. Nat Immunol 15, 521–529 (2014). https://doi.org/10.1038/ni.2892
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ni.2892
This article is cited by
-
High-throughput matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry–based deubiquitylating enzyme assay for drug discovery
Nature Protocols (2020)
-
Vps11 and Vps18 of Vps-C membrane traffic complexes are E3 ubiquitin ligases and fine-tune signalling
Nature Communications (2019)
-
Geoepidemiology and Immunologic Features of Autoinflammatory Diseases: a Comprehensive Review
Clinical Reviews in Allergy & Immunology (2018)
-
Assembly and regulation of ASC specks
Cellular and Molecular Life Sciences (2017)
-
Cellular and molecular regulation of innate inflammatory responses
Cellular & Molecular Immunology (2016)
