Ubiquitin as a regulator of IFN production in the antiviral response
Karolina Matković 1 , Małgorzata Mitkiewicz 1 , Janusz Matuszyk 1Abstract
Type I interferons (IFNs) are important in the immune response. After pathogen detection, host cells rapidly trigger innate immune mechanisms such as inflammatory cytokines production, thus leading to the eradication of the invading virus. Such mechanisms engage signaling cascades which, in the initial phase of infection, lead to the activation of the NF-κB pathway and IFN regulatory factors (IRF-3, IRF-7) which directly control the production of IFNs. Proper regulation of IFN induction takes place by ubiqutination and allows to maintain a balance between the activation and inhibition of the immune system response due to an infection. Studies in recent years indicate that ubiquitination of proteins can affect both proteasomal degradation as well as the non-canonical pathway which results in the regulation of their activity. The type of ubiquitination primarily depends on the attachment of ubiquitin chain to thetarget protein but also on the activity of proteases from DUBs family. The ubiquitin pathway holds many potential therapeutic targets. Thus, the more detailed understanding of the mechanism of ubiquitination and the role of ubiquitin involved in IFNs production pathways may provide a turning point for both antiviral therapy and autoimmune diseases.
References
- 1. Belgnaoui M.S., Paz S., Samuel S., Goulet M.L., Sun Q., Kikkert M.,Iwai K., Dikic I., Hiscott J., Lin R.: Linear ubiquitination of NEMO negativelyregulates the interferon antiviral response through disruptionof the MAVS-TRAF3 complex. Cell Host Microbe, 2012; 12: 211-222
Google Scholar - 2. Bibeau-Poirier A., Gravel S.P., Clément J.F., Rolland S., Rodier G.,Coulombe P., Hiscott J., Grandvaux N., Meloche S., Servant M.J.: Involvementof the IκB kinase (IKK)-related kinases tank-binding kinase1/IKKi and cullin-based ubiquitin ligases in IFN regulatory factor-3degradation. J. Immunol., 2006; 177: 5059-5067
Google Scholar - 3. Bonizzi G., Karin M.: The two NF-κB activation pathways andtheir role in innate and adaptive immunity. Trends Immunol., 2004;25: 280-288
Google Scholar - 4. Bottero V., Rossi F., Samson M., Mari M., Hofman P., Peyron J.F.:IκBα, the NF-κB inhibitory subunit, interacts with ANT, the mitochondrialATP/ADP translocator. J. Biol. Chem., 2001; 276: 21317-21324
Google Scholar - 5. Chen H.W., King K., Tu J., Sanchez M., Luster A.D., Shresta S.: Theroles of IRF-3 and IRF-7 in innate antiviral immunity against denguevirus. J. Immunol., 2013; 191: 4194-4201
Google Scholar - 6. Daffis S., Samuel M.A., Suthar M.S., Keller B.C., Gale M.Jr., DiamondM.S.: Interferon regulatory factor IRF-7 induces the antiviralalpha interferon response and protects against lethal West Nile virusinfection. J. Virol., 2008; 82: 8465-8475
Google Scholar - 7. Dasu M.R., Ramirez S., Isseroff R.R.: Toll-like receptors and diabetes:a therapeutic perspective. Clin. Sci., 2012; 122: 203-214
Google Scholar - 8. Dikic I., Crosetto N., Calatroni S., Bernasconi P.: Targeting ubiquitinin cancers. Eur. J. Cancer, 2006; 42: 3095-3102
Google Scholar - 9. Dolcet X., Llobet D., Pallares J., Matias-Guiu X.: NF-κB in developmentand progression of human cancer. Virchows Arch., 2005;446: 475-482
Google Scholar - 10. Eisenächer K., Krug A.: Regulation of RLR-mediated innate immunesignaling – it is all about keeping the balance. Eur. J. Cell Biol.,2012; 91: 36-47
Google Scholar - 11. Fang D.F., He K., Wang J., Mu R., Tan B., Jian Z., Li H.Y., Song W.,Chang Y., Gong W.L., Li W.H., Wang G.J.: RAD23A negatively regulatesRIG-I/MDA5 signaling through promoting TRAF2 polyubiquitinationand degradation. Biochem. Biophys. Res. Commun., 2013;431: 686-692
Google Scholar - 12. Fulda S., Rajalingam K., Dikic I.: Ubiquitylation in immune disordersand cancer: from molecular mechanisms to therapeuticimplications. EMBO Mol. Med., 2012; 4: 545-556
Google Scholar - 13. Ghosh S., Karin M.: Missing pieces in the NF-κB puzzle. Cell,2002; 109 (Suppl. 1): S81-S96
Google Scholar - 14. Giardino Torchia M.L., Conze D.B., Jankovic D., Ashwell J.D.: Balancebetween NF-κB p100 and p52 regulates T cell costimulationdependence. J. Immunol., 2013; 190: 549-555
Google Scholar - 15. Graff J.W., Ewen J., Ettayebi K., Hardy M.E.: Zinc-binding domainof rotavirus NSP1 is required for proteasome-dependent degradationof IRF3 and autoregulatory NSP1 stability. J. Gen. Virol.,2007; 88: 613-620
Google Scholar - 16. Hayden M.S., Ghosh S.: Signaling to NF-κB. Genes Dev., 2004;18: 2195-2224
Google Scholar - 17. Hedayat M., Netea M.G., Rezaei N.: Targeting of Toll-like receptors:a decade of progress in combating infectious diseases. LancetInfect. Dis., 2011; 11: 702-712
Google Scholar - 18. Hideshima T., Bradner J.E., Chauhan D., Anderson K.C.: Intracellularprotein degradation and its therapeutic implications. Clin.Cancer Res., 2005; 11: 8530-8533
Google Scholar - 19. Higgs R., Jefferies C.A.: Targeting IRFs by ubiquitination: regulatingantiviral responses. Biochem. Soc. Trans., 2008; 36: 453-458
Google Scholar - 20. Honda K., Taniguchi T.: IRFs: master regulators of signallingby Toll-like receptors and cytosolic pattern-recognition receptors.Nat. Rev. Immunol., 2006; 6: 644-658
Google Scholar - 21. Honda K., Yanai H., Negishi H., Asagiri M., Sato M., Mizutani T.,Shimada N., Ohba Y., Takaoka A., Yoshida N., Taniguchi T.: IRF-7 isthe master regulator of type-I interferon-dependent immune responses.Nature, 2005; 434: 772-777
Google Scholar - 22. Huang T.T., Miyamoto S.: Postrepression activation of NF-κBrequires the amino-terminal nuclear export signal specific to IκBα.Mol. Cell. Biol., 2001; 21: 4737-4747
Google Scholar - 23. Huye L.E., Ning S., Kelliher M., Pagano J.S.: Interferon regulatoryfactor 7 is activated by a viral oncoprotein through RIP-dependentubiquitination. Mol. Cell. Biol., 2007; 27: 2910-2918
Google Scholar - 24. Ikeda F., Crosetto N., Dikic I.: What determines the specificityand outcomes of ubiquitin signaling? Cell, 2010; 143: 677-681
Google Scholar - 25. Jabłońska A., Paradowska E.: Rola receptorów RIG-I-podobnychw odpowiedzi przeciwwirusowej. Postępy Hig. Med. Dośw., 2014;68: 541-556
Google Scholar - 26. Kawai T., Akira S.: The role of pattern-recognition receptorsin innate immunity: update on Toll-like receptors. Nat. Immunol.,2010; 11: 373-384
Google Scholar - 27. Kayagaki N., Phung Q., Chan S., Chaudhari R., Quan C., O’RourkeK.M., Eby M., Pietras E., Cheng G., Bazan J.F., Zhang Z., Arnott D.,Dixit V.M.: DUBA: a deubiquitinase that regulates type I interferonproduction. Science, 2007; 318: 1628-1632
Google Scholar - 28. Kędziora S., Słotwiński R.: Molekularne mechanizmy towarzyszącerozpoznawaniu patogenu przez receptory wrodzonej odporności.Postępy Hig. Med. Dośw., 2009; 63: 30-38
Google Scholar - 29. Kirkin V., Dikic I.: Ubiquitin networks in cancer. Curr. Opin. Genet.Dev., 2011; 21: 21-28
Google Scholar - 30. Koshiba T.: Mitochondrial-mediated antiviral immunity. Biochim.Biophys. Acta, 2013; 1833: 225-232
Google Scholar - 31. Koshiba T., Bashiruddin N., Kawabata S.: Mitochondria and antiviralinnate immunity. Int. J. Biochem. Mol. Biol., 2011; 2: 257-262
Google Scholar - 32. Krug A., Luker G.D., Barchet W., Leib D.A., Akira S., Colonna M.:Herpes simplex virus type 1 activates murine natural interferon-producingcells through toll-like receptor 9. Blood, 2004; 103: 1433-1437
Google Scholar - 33. Lee J.Y., Zhao L., Hwang D.H.: Modulation of pattern recognitionreceptor-mediated inflammation and risk of chronic diseasesby dietary fatty acids. Nutr. Rev., 2010; 68: 38-61
Google Scholar - 34. Liu S.Y., Sanchez D.J., Cheng G.: New developments in the inductionand antiviral effectors of type I interferon. Curr. Opin. Immunol.,2011; 23: 57-64
Google Scholar - 35. Luise C., Capra M., Donzelli M., Mazzarol G., Jodice M.G., NuciforoP., Viale G., Di Fiore P.P., Confalonieri S.: An atlas of alteredexpression of deubiquitinating enzymes in human cancer. PLoSOne, 2011; 6: e15891
Google Scholar - 36. Lund J.M., Alexopoulou L., Sato A., Karow M., Adams N.C., Gale N.W.,Iwasaki A., Flavell R.A.: Recognition of single-stranded RNA virusesby Toll-like receptor 7. Proc. Natl. Acad. Sci. USA, 2004; 101: 5598-5603
Google Scholar - 37. Maelfait J., Beyaert R.: Emerging role of ubiquitination in antiviralRIG-I signaling. Microbiol. Mol. Biol. Rev., 2012; 76: 33-45
Google Scholar - 38. Martinez-Forero I., Rouzaut A., Palazon A., Dubrot J., MeleroI.: Lysine 63 polyubiquitination in immunotherapy and in cancer–promoting inflammation. Clin. Cancer Res., 2009; 15: 6751-6757
Google Scholar - 39. Mattern M.R., Wu J., Nicholson B.: Ubiquitin-based anticancertherapy: carpet bombing with proteasome inhibitors vs surgicalstrikes with E1, E2, E3, or DUB inhibitors. Biochim. Biophys. Acta,2012; 1823: 2014-2021
Google Scholar - 40. Molineaux S.M.: Molecular pathways: targeting proteasomalprotein degradation in cancer. Clin. Cancer Res., 2012; 18: 15-20
Google Scholar - 41. Mukhopadhyay D., Riezman H.: Proteasome-independent functionsof ubiquitin in endocytosis and signaling. Science, 2007; 315:201-205
Google Scholar - 42. Niewold T.B.: Interferon alpha-induced lupus: proof of principle.J. Clin. Rheumatol., 2008; 14: 131-132
Google Scholar - 43. Niewold T.B., Adler J.E., Glenn S.B., Lehman T.J., Harley J.B., CrowM.K.: Age- and sex-related patterns of serum interferon-α activityin lupus families. Arthritis Rheum., 2008; 58: 2113-2119
Google Scholar - 44. Ning S., Campos A.D., Darnay B.G., Bentz G.L., Pagano J.S.: TRAF6and the three C-terminal lysine sites on IRF7 are required for itsubiquitination-mediated activation by the tumor necrosis factorreceptor family member latent membrane protein 1. Mol. Cell. Biol.,2008; 28: 6536-6546
Google Scholar - 45. O’Neill L.A., Bryant C.E., Doyle S.L.: Therapeutic targeting ofToll-like receptors for infectious and inflammatory diseases andcancer. Pharmacol. Rev., 2009; 61: 177-197
Google Scholar - 46. Paul S.: Dysfunction of the ubiquitin-proteasome system in multipledisease conditions: therapeutic approaches. Bioessays, 2008;30: 1172-1184
Google Scholar - 47. Poeck H., Ruland J.: From virus to inflammation: Mechanismsof RIG-I-induced IL-1β production. Eur. J. Cell Biol., 2012; 91: 59-64
Google Scholar - 48. Ramos H.J., Gale M.Jr.: RIG-I like receptors and their signalingcrosstalk in the regulation of antiviral immunity. Curr. Opin. Virol.,2011; 1: 167-176
Google Scholar - 49. Rastogi N., Mishra D.P.: Therapeutic targeting of cancer cell cycleusing proteasome inhibitors. Cell Div., 2012; 7: 26
Google Scholar - 50. Sadler A.J., Williams B.R.: Interferon-inducible antiviral effectors.Nat. Rev. Immunol., 2008; 8: 559-568
Google Scholar - 51. Saitoh T., Tun-Kyi A., Ryo A., Yamamoto M., Finn G., Fujita T.,Akira S., Yamamoto N., Lu K.P., Yamaoka S.: Negative regulation ofinterferon-regulatory factor 3-dependent innate antiviral responseby the prolyl isomerase Pin1. Nat. Immunol., 2006; 7: 598-605
Google Scholar - 52. Seth R.B., Sun L., Ea C.K., Chen Z.J.: Identification and characterizationof MAVS, a mitochondrial antiviral signaling protein thatactivates NF-κB and IRF3. Cell, 2005; 122: 669-682
Google Scholar - 53. Sgarbanti M., Marsili G., Remoli A.L., Orsatti R., Battistini A.:IRF-7: new role in the regulation of genes involved in adaptive immunity.Ann. N.Y. Acad. Sci., 2007; 1095: 325-333
Google Scholar - 54. Tak P.P., Firestein G.S.: NF-κB: a key role in inflammatory diseases.J. Clin. Invest., 2001; 107: 7-11
Google Scholar - 55. Takeuchi O., Akira S.: Innate immunity to virus infection. Immunol.Rev., 2009; 227: 75-86
Google Scholar - 56. Takeuchi O., Akira S.: Pattern recognition receptors and inflammation.Cell, 2010; 140: 805-820
Google Scholar - 57. Thompson M.R., Kaminski J.J., Kurt-Jones E.A., Fitzgerald K.A.:Pattern recognition receptors and the innate immune response toviral infection. Viruses, 2011; 3: 920-940
Google Scholar - 58. Tsou W.L., Sheedlo M.J., Morrow M.E., Blount J.R., McGregorK.M., Das C., Todi S.V.: Systematic analysis of the physiological importanceof deubiquitinating enzymes. PLoS One, 2012; 7: e43112
Google Scholar - 59. Wang J., Maldonado M.A.: The ubiquitin-proteasome systemand its role in inflammatory and autoimmune diseases. Cell. Mol.Immunol., 2006; 3: 255-261
Google Scholar - 60. Yuk J.M., Jo E.K.: Toll-like receptors and innate immunity. J.Bacteriol. Virol., 2011; 41: 225-235
Google Scholar - 61. Zeng W., Xu M., Liu S., Sun L., Chen Z.J.: Key role of Ubc5 andlysine-63 polyubiquitination in viral activation of IRF3. Mol. Cell,2009; 36: 315-325
Google Scholar