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Ubiquitination-Mediated NF-κB Regulation in Inflammatory Response

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Protein Modifications in Pathogenic Dysregulation of Signaling

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Abstract

Nuclear factor (NF)-κB is a central signaling pathway regulating inflammatory, adaptive, and innate immune responses, and impaired NF-κB activity is implicated in multiple disorders, including cancer, autoimmune, inflammatory, and neurodegenerative diseases, and metabolic syndrome. Lys63 (K63)- and K48-linked polyubiquitin chains, catalyzed by specific ubiquitin ligases (E3s) such as TNF receptor-associated factor (TRAF), inhibitor of apoptosis (IAP), and β-TrCP, are involved in the NF-κB pathway. In addition, we found a ubiquitin ligase complex named LUBAC (linear ubiquitin chain assembly complex), composed of HOIL-1L, HOIP, and SHARPIN. LUBAC generates a novel type of Met1 (M1)-linked linear polyubiquitin chain, which serves as a scaffold to recruit IκB kinase (IKK), and then activates IKK auto-catalytically by trans-phosphorylation. Genetic ablation and polymorphism of LUBAC subunits induces multiple disorders, including dermatitis, autoinflammation, immunodeficiency, and B-cell lymphomas. Moreover, specific deubiquitinases (DUBs), such as A20 (TNFAIP3), OTULIN/gumby, and CYLD, suppress NF-κB activation by a separate molecular basis, and genetic mutations of these DUBs cause disorders such as cancer. This review summarizes the various types of ubiquitination-mediated NF-κB regulation by E3s and DUBs. Moreover, the pathophysiological implications of these proteins, especially on inflammatory responses by cytokines and pathogens, are summarized.

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References

  • Belgnaoui SM, Paz S, Samuel S, Goulet ML, Sun Q, Kikkert M, Iwai K, Dikic I, Hiscott J, Lin R (2012) Linear ubiquitination of NEMO negatively regulates the interferon antiviral response through disruption of the MAVS-TRAF3 complex. Cell Host Microbe 12:211–222

    Article  CAS  PubMed  Google Scholar 

  • Berger SB, Kasparcova V, Hoffman S, Swift B, Dare L, Schaeffer M, Capriotti C, Cook M, Finger J, Hughes-Earle A et al (2014) Cutting edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice. J Immunol 192:5476–5480

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Beug ST, Cheung HH, LaCasse EC, Korneluk RG (2012) Modulation of immune signalling by inhibitors of apoptosis. Trends Immunol 33:535–545

    Article  CAS  PubMed  Google Scholar 

  • Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, Abhyankar A, Israel L, Trevejo-Nunez G, Bogunovic D et al (2012) Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol 13:1178–1186

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bosanac I, Wertz IE, Pan B, Yu C, Kusam S, Lam C, Phu L, Phung Q, Maurer B, Arnott D et al (2010) Ubiquitin binding to A20 ZnF4 is required for modulation of NF-κB signaling. Mol Cell 40:548–557

    Article  CAS  PubMed  Google Scholar 

  • Christiaens I, Zaragoza DB, Guilbert L, Robertson SA, Mitchell BF, Olson DM (2008) Inflammatory processes in preterm and term parturition. J Reprod Immunol 79:50–57

    Article  CAS  PubMed  Google Scholar 

  • Damgaard RB, Nachbur U, Yabal M, Wong WW, Fiil BK, Kastirr M, Rieser E, Rickard JA, Bankovacki A, Peschel C et al (2012) The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol Cell 46:746–758

    Article  CAS  PubMed  Google Scholar 

  • De A, Dainichi T, Rathinam CV, Ghosh S (2014) The deubiquitinase activity of A20 is dispensable for NF-κB signaling. EMBO Rep 15:775–783

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dynek JN, Goncharov T, Dueber EC, Fedorova AV, Izrael-Tomasevic A, Phu L, Helgason E, Fairbrother WJ, Deshayes K, Kirkpatrick DS et al (2010) c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J 29:4198–4209

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Elliott PR, Nielsen SV, Marco-Casanova P, Fiil BK, Keusekotten K, Mailand N, Freund SM, Gyrd-Hansen M, Komander D (2014) Molecular basis and regulation of OTULIN-LUBAC interaction. Mol Cell 54:335–348

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Emmerich CH, Ordureau A, Strickson S, Arthur JS, Pedrioli PG, Komander D, Cohen P (2013) Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains. Proc Natl Acad Sci U S A 110:15247–15252

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fujita H, Rahighi S, Akita M, Kato R, Sasaki Y, Wakatsuki S, Iwai K (2014) Mechanism underlying IκB kinase activation mediated by the linear ubiquitin chain assembly complex. Mol Cell Biol 34:1322–1335

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Garlanda C, Dinarello CA, Mantovani A (2013) The interleukin-1 family: back to the future. Immunity 39:1003–1018

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gerlach B, Cordier SM, Schmukle AC, Emmerich CH, Rieser E, Haas TL, Webb AI, Rickard JA, Anderton H, Wong WW et al (2011) Linear ubiquitination prevents inflammation and regulates immune signalling. Nature (Lond) 471:591–596

    Article  CAS  Google Scholar 

  • Haas TL, Emmerich CH, Gerlach B, Schmukle AC, Cordier SM, Rieser E, Feltham R, Vince J, Warnken U, Wenger T et al (2009) Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol Cell 36:831–844

    Article  CAS  PubMed  Google Scholar 

  • Harhaj EW, Dixit VM (2011) Deubiquitinases in the regulation of NF-κB signaling. Cell Res 21:22–39

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hayden MS, Ghosh S (2012) NF-κB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev 26:203–234

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hershko A, Ciechanover A (1992) The ubiquitin system for protein degradation. Annu Rev Biochem 61:761–807

    Article  CAS  PubMed  Google Scholar 

  • HogenEsch H, Gijbels MJ, Offerman E, van Hooft J, van Bekkum DW, Zurcher C (1993) A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice. Am J Pathol 143:972–982

    CAS  PubMed Central  PubMed  Google Scholar 

  • HogenEsch H, Janke S, Boggess D, Sundberg JP (1999) Absence of Peyer’s patches and abnormal lymphoid architecture in chronic proliferative dermatitis (cpdm/cpdm) mice. J Immunol 162:3890–3896

    CAS  PubMed  Google Scholar 

  • Hostager BS, Fox DK, Whitten D, Wilkerson CG, Eipper BA, Francone VP, Rothman PB, Colgan JD (2010) HOIL-1L interacting protein (HOIP) as an NF-κB regulating component of the CD40 signaling complex. PLoS One 5:e11380

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hostager BS, Kashiwada M, Colgan JD, Rothman PB (2011) HOIL-1L interacting protein (HOIP) is essential for CD40 signaling. PLoS One 6:e23061

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hymowitz SG, Wertz IE (2010) A20: from ubiquitin editing to tumour suppression. Nat Rev Cancer 10:332–341

    Article  CAS  PubMed  Google Scholar 

  • Ikeda F, Deribe YL, Skanland SS, Stieglitz B, Grabbe C, Franz-Wachtel M, van Wijk SJ, Goswami P, Nagy V, Terzic J et al (2011) SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis. Nature (Lond) 471:637–641

    Article  CAS  Google Scholar 

  • Inn KS, Gack MU, Tokunaga F, Shi M, Wong LY, Iwai K, Jung JU (2011) Linear ubiquitin assembly complex negatively regulates RIG-I- and TRIM25-mediated type I interferon induction. Mol Cell 41:354–365

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Iwai K (2012) Diverse ubiquitin signaling in NF-κB activation. Trends Cell Biol 22:355–364

    Article  CAS  PubMed  Google Scholar 

  • Kanarek N, Ben-Neriah Y (2012) Regulation of NF-κB by ubiquitination and degradation of the IκBs. Immunol Rev 246:77–94

    Article  CAS  PubMed  Google Scholar 

  • Kanayama A, Seth RB, Sun L, Ea CK, Hong M, Shaito A, Chiu YH, Deng L, Chen ZJ (2004) TAB2 and TAB3 activate the NF-κB pathway through binding to polyubiquitin chains. Mol Cell 15:535–548

    Article  CAS  PubMed  Google Scholar 

  • Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, Niwa A, Chen Y, Nakazaki K, Nomoto J et al (2009) Frequent inactivation of A20 in B-cell lymphomas. Nature (Lond) 459:712–716

    Article  CAS  Google Scholar 

  • Kensche T, Tokunaga F, Ikeda F, Goto E, Iwai K, Dikic I (2012) 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Keusekotten K, Elliott PR, Glockner L, Fiil BK, Damgaard RB, Kulathu Y, Wauer T, Hospenthal MK, Gyrd-Hansen M, Krappmann D et al (2013) OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin. Cell 153:1312–1326

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kirisako T, Kamei K, Murata S, Kato M, Fukumoto H, Kanie M, Sano S, Tokunaga F, Tanaka K, Iwai K (2006) A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J 25:4877–4887

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Komander D, Rape M (2012) The ubiquitin code. Annu Rev Biochem 81:203–229

    Article  CAS  PubMed  Google Scholar 

  • Komander D, Clague MJ, Urbe S (2009a) Breaking the chains: structure and function of the deubiquitinases. Nat Rev Mol Cell Biol 10:550–563

    Article  CAS  PubMed  Google Scholar 

  • Komander D, Reyes-Turcu F, Licchesi JD, Odenwaelder P, Wilkinson KD, Barford D (2009b) Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. EMBO Rep 10:466–473

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lim S, Sala C, Yoon J, Park S, Kuroda S, Sheng M, Kim E (2001) Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins. Mol Cell Neurosci 17:385–397

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Han C, Xie B, Wu Y, Liu S, Chen K, Xia M, Zhang Y, Song L, Li Z et al (2014) Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO. Nat Immunol 15:612–622

    Article  CAS  PubMed  Google Scholar 

  • Niu J, Shi Y, Iwai K, Wu ZH (2011) LUBAC regulates NF-κB activation upon genotoxic stress by promoting linear ubiquitination of NEMO. EMBO J 30:3741–3753

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pauli EK, Chan YK, Davis ME, Gableske S, Wang MK, Feister KF, Gack MU (2014) The ubiquitin-specific protease USP15 promotes RIG-I-mediated antiviral signaling by deubiquitylating TRIM25. Sci Signal 7:ra3

    Google Scholar 

  • Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, Kensche T, Uejima T, Bloor S, Komander D et al (2009) Specific recognition of linear ubiquitin chains by NEMO is important for NF-κB activation. Cell 136:1098–1109

    Article  CAS  PubMed  Google Scholar 

  • Rivkin E, Almeida SM, Ceccarelli DF, Juang YC, MacLean TA, Srikumar T, Huang H, Dunham WH, Fukumura R, Xie G et al (2013) The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis. Nature (Lond) 498:318–324

    Article  CAS  Google Scholar 

  • Sasaki Y, Sano S, Nakahara M, Murata S, Kometani K, Aiba Y, Sakamoto S, Watanabe Y, Tanaka K, Kurosaki T et al (2013) Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells. EMBO J 32:2463–2476

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sato Y, Fujita H, Yoshikawa A, Yamashita M, Yamagata A, Kaiser SE, Iwai K, Fukai S (2011) Specific recognition of linear ubiquitin chains by the Npl4 zinc finger (NZF) domain of the HOIL-1L subunit of the linear ubiquitin chain assembly complex. Proc Natl Acad Sci U S A 108:20520–20525

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schaeffer V, Akutsu M, Olma MH, Gomes LC, Kawasaki M, Dikic I (2014) Binding of OTULIN to the PUB domain of HOIP controls NF-κB signaling. Mol Cell 54:349–361

    Article  CAS  PubMed  Google Scholar 

  • Smit JJ, Monteferrario D, Noordermeer SM, van Dijk WJ, van der Reijden BA, Sixma TK (2012) The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR-RING domain and the unique LDD extension. EMBO J 31:3833–3844

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stieglitz B, Morris-Davies AC, Koliopoulos MG, Christodoulou E, Rittinger K (2012) LUBAC synthesizes linear ubiquitin chains via a thioester intermediate. EMBO Rep 13:840–846

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stieglitz B, Rana RR, Koliopoulos MG, Morris-Davies AC, Schaeffer V, Christodoulou E, Howell S, Brown NR, Dikic I, Rittinger K (2013) Structural basis for ligase-specific conjugation of linear ubiquitin chains by HOIP. Nature (Lond) 503:422–426

    Article  CAS  Google Scholar 

  • Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140:805–820

    Article  CAS  PubMed  Google Scholar 

  • Takiuchi T, Nakagawa T, Tamiya H, Fujita H, Sasaki Y, Saeki Y, Takeda H, Sawasaki T, Buchberger A, Kimura T et al (2014) Suppression of LUBAC-mediated linear ubiquitination by a specific interaction between LUBAC and the deubiquitinases CYLD and OTULIN. Genes Cells 19:254–272

    Article  CAS  PubMed  Google Scholar 

  • Tamiya H, Terao M, Takiuchi T, Nakahara M, Sasaki Y, Katayama I, Yoshikawa H, Iwai K (2014) IFN-γ or IFN-α ameliorates chronic proliferative dermatitis by inducing expression of linear ubiquitin chain assembly complex. J Immunol 192:3793–3804

    Article  CAS  PubMed  Google Scholar 

  • Tarantino N, Tinevez JY, Crowell EF, Boisson B, Henriques R, Mhlanga M, Agou F, Israel A, Laplantine E (2014) TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO-IKK supramolecular structures. J Cell Biol 204:231–245

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tokunaga F (2013) Linear ubiquitination-mediated NF-κB regulation and its related disorders. J Biochem (Tokyo) 154:313–323

    Article  CAS  Google Scholar 

  • Tokunaga F, Iwai K (2012) Linear ubiquitination: a novel NF-κB regulatory mechanism for inflammatory and immune responses by the LUBAC ubiquitin ligase complex. Endocr J 59:641–652

    Article  CAS  PubMed  Google Scholar 

  • Tokunaga F, Sakata S, Saeki Y, Satomi Y, Kirisako T, Kamei K, Nakagawa T, Kato M, Murata S, Yamaoka S et al (2009) Involvement of linear polyubiquitylation of NEMO in NF-κB activation. Nat Cell Biol 11:123–132

    Article  CAS  PubMed  Google Scholar 

  • Tokunaga F, Nakagawa T, Nakahara M, Saeki Y, Taniguchi M, Sakata S, Tanaka K, Nakano H, Iwai K (2011) SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex. Nature (Lond) 471:633–636

    Article  CAS  Google Scholar 

  • Tokunaga F, Nishimasu H, Ishitani R, Goto E, Noguchi T, Mio K, Kamei K, Ma A, Iwai K, Nureki O (2012) Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-κB regulation. EMBO J 31:3856–3870

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Vallabhapurapu S, Karin M (2009) Regulation and function of NF-κB transcription factors in the immune system. Annu Rev Immunol 27:693–733

    Article  CAS  PubMed  Google Scholar 

  • Vallabhapurapu S, Matsuzawa A, Zhang W, Tseng PH, Keats JJ, Wang H, Vignali DA, Bergsagel PL, Karin M (2008) Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling. Nat Immunol 9:1364–1370

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Varfolomeev E, Goncharov T, Maecker H, Zobel K, Komuves LG, Deshayes K, Vucic D (2012) Cellular inhibitors of apoptosis are global regulators of NF-κB and MAPK activation by members of the TNF family of receptors. Sci Signal 5:ra22

    Google Scholar 

  • Verhelst K, Carpentier I, Kreike M, Meloni L, Verstrepen L, Kensche T, Dikic I, Beyaert R (2012) A20 inhibits LUBAC-mediated NF-κB activation by binding linear polyubiquitin chains via its zinc finger 7. EMBO J 31:3845–3855

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Walczak H (2011) TNF and ubiquitin at the crossroads of gene activation, cell death, inflammation, and cancer. Immunol Rev 244:9–28

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature (Lond) 412:346–351

    Article  CAS  Google Scholar 

  • Wertz IE, O’Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL et al (2004) De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling. Nature (Lond) 430:694–699

    Article  CAS  Google Scholar 

  • Xie P (2013) TRAF molecules in cell signaling and in human diseases. J Mol Signal 8:7

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Xu M, Skaug B, Zeng W, Chen ZJ (2009) A ubiquitin replacement strategy in human cells reveals distinct mechanisms of IKK activation by TNF-α and IL-1β. Mol Cell 36:302–314

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yagi H, Ishimoto K, Hiromoto T, Fujita H, Mizushima T, Uekusa Y, Yagi-Utsumi M, Kurimoto E, Noda M, Uchiyama S et al (2012) A non-canonical UBA-UBL interaction forms the linear-ubiquitin-chain assembly complex. EMBO Rep 13:462–468

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yamamoto M, Okamoto T, Takeda K, Sato S, Sanjo H, Uematsu S, Saitoh T, Yamamoto N, Sakurai H, Ishii KJ et al (2006) Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling. Nat Immunol 7:962–970

    Article  CAS  PubMed  Google Scholar 

  • Yamanaka K, Ishikawa H, Megumi Y, Tokunaga F, Kanie M, Rouault TA, Morishima I, Minato N, Ishimori K, Iwai K (2003) Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2. Nat Cell Biol 5:336–340

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Schmitz R, Mitala J, Whiting A, Xiao W, Ceribelli M, Wright GW, Zhao H, Yang Y, Xu W et al (2014) Essential role of the linear ubiquitin chain assembly complex in lymphoma revealed by rare germline polymorphisms. Cancer Discov 4:480–493

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zelova H, Hosek J (2013) TNF-α signalling and inflammation: interactions between old acquaintances. Inflamm Res 62:641–651

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Tian Y, Wang RP, Gao D, Zhang Y, Diao FC, Chen DY, Zhai ZH, Shu HB (2008) Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3. Cell Res 18:1096–1104

    Article  CAS  PubMed  Google Scholar 

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  1. Laboratory of Molecular Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, 371-8512, Japan

    Fuminori Tokunaga

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Correspondence to Fuminori Tokunaga .

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  1. Division of Cellular & Molecular Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Jun-ichiro Inoue

  2. The Institute of Medical Science Division of Cell Signaling & Molecular Medicine, The University of Tokyo, Tokyo, Japan

    Mutsuhiro Takekawa

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Tokunaga, F. (2015). Ubiquitination-Mediated NF-κB Regulation in Inflammatory Response. In: Inoue, Ji., Takekawa, M. (eds) Protein Modifications in Pathogenic Dysregulation of Signaling. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55561-2_12

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