Advertisement

Post-translational modification of the death receptor complex as a potential therapeutic target in cancer

  • Kidong Kang
  • So-Ra Lee
  • Xuezhe Piao
  • Gang Min Hur
Review
  • 174 Downloads

Abstract

Programmed cell death is critical to the physiological function of multi-cellular organisms, controlling development, immunity, inflammation, and cancer progression. Death receptor (DR)-mediated regulation of a protease functions as a second messenger to initiate a death signal cascade to induce apoptosis or necroptosis. Recently, it has become clear that post-translational modifications (PTMs) of signaling components in the DR complex are highly complex, temporally controlled, and tightly regulated, and play an important role in cell death signaling. This review focuses on the molecular mechanisms and pathophysiological consequences of PTMs on the formation of the DR signaling complex, especially with respect to tumor necrosis factor receptor 1 (TNFR1). Furthermore, characterization of the role of PTMs in spatially different TNFR1 complexes (complexes I and II), especially with respect to the role of ubiquitination and phosphorylation of receptor interacting protein 1 (RIP1) in programmed cell death in cancer cells, will be reviewed. By integrating recently gained insight of the functional importance of PTMs in complex I or II, this review discusses how the concerted action of PTMs results in life or death upon DR ligation. Finally, the emerging concept of a sequential cell death checkpoint by the PTMs of RIP1, which may reveal novel therapeutic opportunities for the treatment of some cancers, will be discussed.

Keywords

Death receptor Post-translational modification Receptor signaling complex Cell death checkpoint Tumor necrosis factor 

Notes

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (Grant Nos. 2017R1A2A1A05001225, 2017R1A5A2015385).

Compliance with ethical standards

Conflict of interest

The authors declared no conflict of interest.

References

  1. Alameda JP, Fernández-Aceñero MJ, Moreno-Maldonado R, Navarro M, Quintana R, Page A, Ramírez A, Bravo A, Casanova ML (2011) CYLD regulates keratinocyte differentiation and skin cancer progression in humans. Cell Death Dis. 2:e208CrossRefGoogle Scholar
  2. Annibaldi A, Meier P (2018) Checkpoints in TNF-induced cell death: implications in inflammation and cancer. Trends Mol Med 24:49–65CrossRefGoogle Scholar
  3. Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281:1305–1308CrossRefGoogle Scholar
  4. Bagnoli M, Canevari S, Mezzanzanica D (2010) Cellular FLICE-inhibitory protein (c-FLIP) signalling: a key regulator of receptor-mediated apoptosis in physiologic context and in cancer. Int J Biochem Cell Biol 42:210–213CrossRefGoogle Scholar
  5. Baker SJ, Reddy EP (1998) Modulation of life and death by the TNF receptor superfamily. Oncogene 17:3261–3270CrossRefGoogle Scholar
  6. Balkwill F (2009) Tumour necrosis factor and cancer. Nat Rev Cancer 9:361–371CrossRefGoogle Scholar
  7. Barbero S, Barilà D, Mielgo A, Stagni V, Clair K, Stupack D (2008) Identification of a critical tyrosine residue in caspase 8 that promotes cell migration. J Biol Chem 283:13031–13034CrossRefGoogle Scholar
  8. Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, Gillard JW, Jaquith JB, Morris SJ, Barker PA (2008) cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell 30:689–700CrossRefGoogle Scholar
  9. Blackwell K, Zhang L, Workman LM, Ting AT, Iwai K, Habelhah H (2013) Two coordinated mechanisms underlie tumor necrosis factor alpha-induced immediate and delayed IκB kinase activation. Mol Cell Biol 33:1901–1915CrossRefGoogle Scholar
  10. Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, Abhyankar A, Israël L, Trevejo-Nunez G, Bogunovic D, Cepika A-M, MacDuff D, Chrabieh M, Hubeau M, Bajolle F, Debré M, Mazzolari E, Vairo D, Agou F, Virgin HW, Bossuyt X, Rambaud C, Facchetti F, Bonnet D, Quartier P, Fournet J-C, Pascual V, Chaussabel D, Notarangelo LD, Puel A, Israël A, Casanova J-L, Picard C (2012) Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol 13(12):1178–1186CrossRefGoogle Scholar
  11. Brenner D, Blaser H, Mak TW (2015) Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunol 15:362–374CrossRefGoogle Scholar
  12. Chen G, Goeddel DV (2002) TNF-R1 signaling: a beautiful pathway. Science 296:1634–1635CrossRefGoogle Scholar
  13. Chen ZJ, Sun LJ (2009) Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell 33:275–286CrossRefGoogle Scholar
  14. Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM (1995) FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosis. Cell 81(4):505–512CrossRefGoogle Scholar
  15. Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137:1112–1123CrossRefGoogle Scholar
  16. Dannappel M, Vlantis K, Kumari S, Polykratis A, Kim C, Wachsmuth L, Eftychi C, Lin J, Corona T, Hermance N, Zelic M, Kirsch P, Basic M, Bleich A, Kelliher M, Pasparakis M (2014) RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 513:90–94CrossRefGoogle Scholar
  17. De Melo J, Tang D (2015) Elevation of SIPL1 (SHARPIN) increases breast cancer risk. PLoS ONE 10:e0127546CrossRefGoogle Scholar
  18. Degterev A, Hitomi J, Germscheid M, Ch’en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4:313–321CrossRefGoogle Scholar
  19. Degterev A, Maki JL, Yuan Y (2013) Activity and specificity of necrostatin-1, small-molecule inhibitor of RIP1 kinase. Cell Death Differ 20:366CrossRefGoogle Scholar
  20. Dondelinger Y, Aguileta MA, Goossens V, Dubuisson C, Grootjans S, Dejardin E, Vandenabeele P, Bertrand MJ (2013) RIPK3 contributes to TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion or TAK1 kinase inhibition. Cell Death Differ 20:1381–1392CrossRefGoogle Scholar
  21. Dondelinger Y, Jouan-Lanhouet S, Divert T, Theatre E, Bertin J, Gough PJ, Giansanti P, Heck AJ, Dejardin E, Vandenabeele P, Bertrand MJ (2015) NF-κB-independent role of IKKα/IKKβ in preventing RIPK1 kinase-dependent apoptotic and necroptotic cell death during TNF signaling. Mol Cell 60:63–76CrossRefGoogle Scholar
  22. Dondelinger Y, Delanghe T, Rojas-Rivera D, Priem D, Delvaeye T, Bruggeman I, Van Herreweghe F, Vandenabeele P, Bertrand MJM (2017) MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death. Nat Cell Biol 19:1237–1247CrossRefGoogle Scholar
  23. Dynek JN, Goncharov T, Dueber EC, Fedorova AV, Izrael-Tomasevic A, Phu L, Helgason E, Fairbrother WJ, Deshayes K, Kirkpatrick DS, Vucic D (2010) c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J 29:4198–4209CrossRefGoogle Scholar
  24. Dziedzic SA, Su Z, Jean Barrett V, Najafov A, Mookhtiar AK, Amin P, Pan H, Sun L, Zhu H, Ma A, Abbott DW, Yuan J (2018) ABIN-1 regulates RIPK1 activation by linking Met1 ubiquitylation with Lys63 deubiquitylation in TNF-RSC. Nat Cell Biol 20:58–68CrossRefGoogle Scholar
  25. Ea C-K, Deng L, Xia Z-P, Pineda G, Chen ZJ (2006) Activation of IKK by TNFα requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell 22(2):245–257CrossRefGoogle Scholar
  26. Feoktistova M, Geserick P, Kellert B, Dimitrova DP, Langlais C, Hupe M, Cain K, MacFarlane M, Häcker G, Leverkus M (2011) cIAPs block ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol Cell 43:449–463CrossRefGoogle Scholar
  27. Fu T, Lv X, Kong Q, Yuan CA (2017) novel SHARPIN-PRMT5-H3R2me1 axis is essential for lung cancer cell invasion. Oncotarget 8:54809–54820Google Scholar
  28. Fulda S (2015) Promises and challenges of smac mimetics as cancer therapeutics. Clin Cancer Res 21:5030–5036CrossRefGoogle Scholar
  29. Geng J, Ito Y, Shi L, Amin P, Chu J, Ouchida AT, Mookhtiar AK, Zhao H, Xu D, Shan B, Najafov A, Gao G, Akira S, Yuan J (2017) Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates apoptosis and necroptosis. Nat Commun 8:359CrossRefGoogle Scholar
  30. Gentle IE, Wong WW, Evans JM, Bankovacki A, Cook WD, Khan NR, Nachbur U, Rickard J, Anderton H, Moulin M, Lluis JM, Moujalled DM, Silke J, Vaux DL (2011) In TNF-stimulated cells, RIPK1 promotes cell survival by stabilizing TRAF2 and cIAP1, which limits induction of non-canonical NF-kappaB and activation of caspase-8. J Biol Chem 286:13282–13291CrossRefGoogle Scholar
  31. Gustafsson N, Zhao C, Gustafsson JA, Dahlman-Wright K (2010) RBCK1 drives breast cancer cell proliferation by promoting transcription of estrogen receptor alpha and cyclin B1. Cancer Res 70:1265–1274CrossRefGoogle Scholar
  32. Haas TL, Emmerich CH, Gerlach B, Schmukle AC, Cordier SM, Rieser E, Feltham R, Vince J, Warnken U, Wenger T, Koschny R, Komander D, Silke J, Walczak H (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 36:831–844CrossRefGoogle Scholar
  33. Häcker H, Karin M (2006) Regulation and function of IKK and IKK-related kinases. Sci STKE 357:re13Google Scholar
  34. Hellerbrand C, Bumes E, Bataille F, Dietmaier W, Massoumi R, Bosserhoff AK (2007) Reduced expression of CYLD in human colon and hepatocellular carcinomas. Carcinogenesis 28:21–27CrossRefGoogle Scholar
  35. Hsu H, Shu HB, Pan MG, Goeddel DV (1996) TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84:299–308CrossRefGoogle Scholar
  36. Hughes MA, Powley IR, Jukes-Jones R, Horn S, Feoktistova M, Fairall L, Schwabe JW, Leverkus M, Cain K, MacFarlane M (2016) Co-operative and hierarchical binding of c-FLIP and caspase-8: a unified model defines how c-FLIP isoforms differentially control cell fate. Mol Cell 61:834–849CrossRefGoogle Scholar
  37. Ikeda F, Deribe YL, Skånland SS, Stieglitz B, Grabbe C, Franz-Wachtel M, van Wijk SJ, Goswami P, Nagy V, Terzic J, Tokunaga F, Androulidaki A, Nakagawa T, Pasparakis M, Iwai K, Sundberg JP, Schaefer L, Rittinger K, Macek B, Dikic I (2011) SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis. Nature 471:637–641CrossRefGoogle Scholar
  38. Jaco I, Annibaldi A, Lalaoui N, Wilson R, Tenev T, Laurien L, Kim C, Jamal K, Wicky John S, Liccardi G, Chau D, Murphy JM, Brumatti G, Feltham R, Pasparakis M, Silke J, Meier P (2017) MK2 phosphorylates RIPK1 to prevent TNF-induced cell death. Mol Cell 6:698–710CrossRefGoogle Scholar
  39. Jenner MW, Leone PE, Walker BA, Ross FM, Johnson DC, Gonzalez D, Chiecchio L, Dachs Cabanas E, Dagrada GP, Nightingale M, Protheroe RK, Stockley D, Else M, Dickens NJ, Cross NC, Davies FE, Morgan GJ (2007) Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma. Blood 110:3291–3300CrossRefGoogle Scholar
  40. Kanayama A, Seth RB, Sun L, Ea CK, Hong M, Shaito A, Chiu YH, Deng L, Chen ZJ (2004) TAB 2 and TAB 3 activate the NF-κB pathway through binding to polyubiquitin chains. Mol Cell 15:535–548CrossRefGoogle Scholar
  41. Karin M, Lin A (2002) NF-kappaB at the crossroads of life and death. Nat Immunol 3:221–227CrossRefGoogle Scholar
  42. Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, Niwa A, Chen Y, Nakazaki K, Nomoto J, Asakura Y, Muto S, Tamura A, Iio M, Akatsuka Y, Hayashi Y, Mori H, Igarashi T, Kurokawa M, Chiba S, Mori S, Ishikawa Y, Okamoto K, TobinaiK Nakagama H, Nakahata T, Yoshino T, Kobayashi Y, Ogawa S (2009) Frequent inactivation of A20 in B-cell lymphomas. Nature 459:712–716CrossRefGoogle Scholar
  43. Kavuri SM, Geserick P, Berg D, Dimitrova DP, Feoktistova M, Siegmund D, Gollnick H, Neumann M, Wajant H, Leverkus M (2011) Cellular FLICE-inhibitory protein (cFLIP) isoforms block CD95- and TRAIL death receptor-induced gene induction irrespective of processing of caspase-8 or cFLIP in the death-inducing signaling complex. J Biol Chem 286:16631–16646CrossRefGoogle Scholar
  44. Kersse K, Verspurten J, Vanden Berghe T, Vandenabeele P (2011) The death-fold superfamily of homotypic interaction motifs. Trends Biochem Sci 36:541–552CrossRefGoogle Scholar
  45. Kharman-Biz A, Gao H, Ghiasvand R, Haldosen L-A, Zendehdel K, Ahmad A (2018) Expression of the three components of linear ubiquitin assembly complex in breast cancer. PLOS ONE 13(5):e0197183CrossRefGoogle Scholar
  46. Kischkel FC, Hellbardt S, Behrmann I (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J 14:5579–5588CrossRefGoogle Scholar
  47. Kobayashi T, Masoumi KC, Massoumi R (2015) Deubiquitinating activity of CYLD is impaired by SUMOylation in neuroblastoma cells. Oncogene 34:2251–2260CrossRefGoogle Scholar
  48. Komander D, Rape M (2012) The ubiquitin code. Annu Rev Biochem 81:203–229CrossRefGoogle Scholar
  49. Lalaoui N, Hänggi K, Brumatti G, Chau D, Nguyen NY, Vasilikos L, DA SpilgiesLM Heckmann, Ma C, Ghisi M, Salmon JM, Matthews GM, de Valle E, Moujalled DM, Menon MB, Spall SK, Glaser SP, Richmond J, Lock RB, Condon SM, Gugasyan R, Gaestel M, Guthridge M, Johnstone RW, Munoz L, Wei A, Ekert PG, Vaux DL, Wong WW, Silke J (2016) Targeting p38 or MK2 enhances the anti-leukemic activity of smac-mimetics. Cancer Cell 29:145–158CrossRefGoogle Scholar
  50. Lee HW, Lee SH, Lee HW, Ryu YW, Kwon MH, Kim YS (2005) Homomeric and heteromeric interactions of the extracellular domains of death receptors and death decoy receptors. Biochem Biophys Res Commun 330:1205–1212CrossRefGoogle Scholar
  51. Li Q, Van Antwerp D, Mercurio F, Lee KF, Verma IM (1999) Severe liver degeneration in mice lacking the IkappaB kinase 2 gene. Science 284:321–325CrossRefGoogle Scholar
  52. Liu Y, Fan C, Zhang Y, Yu X, Wu X, Zhang X, Zhao Q, Zhang H, Xie Q, Li M, Li X, Ding Q, Ying H, Li D, Zhang H (2017) RIP1 kinase activity-dependent roles in embryonic development of Fadd-deficient mice. Cell Death Differ 24:1459–1469CrossRefGoogle Scholar
  53. Menon MB, Gropengießer J, Fischer J, Novikova L, Deuretzbacher A, Lafera J, Schimmeck H, Czymmeck N, Ronkina N, Kotlyarov A, Aepfelbacher M, Gaestel M, Ruckdeschel K (2017) p38MAPK/MK2 dependent phosphorylation controls cytotoxic RIPK1 signaling in inflammation and infection. Nat Cell Biol 19:1248–1259CrossRefGoogle Scholar
  54. Micheau O, Tschopp J (2003) Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114:181–190CrossRefGoogle Scholar
  55. Najjar M, Suebsuwong C, Ray SS, Thapa RJ, Maki JL, Nogusa S, Shah S, Saleh D, Gough PJ, Bertin J, Yuan J, Balachandran S, Cuny GD, Degterev A (2015) Structure guided design of potent and selective ponatinib-based hybrid inhibitors for RIPK1. Cell Rep 10:1850–1860CrossRefGoogle Scholar
  56. Narayan N, Lee IH, Borenstein R, Sun J, Wong R, Tong G, Fergusson MM, Liu J, Rovira II, Cheng HL, Wang G, Gucek M, Lombard D, Alt FW, Sack MN, Murphy E, Cao L, Finkel T (2012) The NAD-dependent deacetylase SIRT2 is required for programmed necrosis. Nature 492:199–204CrossRefGoogle Scholar
  57. O’Donnell MA, Legarda-Addison D, Skountzos P, Yeh WC, Ting AT (2007) Ubiquitination of RIP1 regulates an NF-kappaB-independent cell-death switch in TNF signaling. Curr Biol 17:418–424CrossRefGoogle Scholar
  58. Oztürk S, Schleich K, Lavrik IN (2012) Cellular FLICE-like inhibitory proteins (c-FLIPs): fine-tuners of life and death decisions. Exp Cell Res 318:1324–1331CrossRefGoogle Scholar
  59. Peltzer N, Rieser E, Taraborrelli L, Draber P, Darding M, Pernaute B, Shimizu Y, Sarr A, Draberova H, Montinaro A, Martinez-Barbera JP, Silke J, Rodriguez TA, Walczak H (2014) HOIP deficiency causes embryonic lethality by aberrant TNFR1-mediated endothelial cell death. Cell Rep 9:153–165CrossRefGoogle Scholar
  60. Pennarun B, Meijer A, de Vries EG, Kleibeuker JH, Kruyt F, de Jong S (2010) Playing the DISC: turning on TRAIL death receptor-mediated apoptosis in cancer. Biochim Biophys Acta 1805:123–140Google Scholar
  61. Pham CG, Bubici C, Zazzeroni F, Papa S, Jones J, Alvarez K, Jayawardena S, De Smaele E, Cong R, Beaumont C, Torti FM, Torti SV, Franzoso G (2004) Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species. Cell 119:529–542CrossRefGoogle Scholar
  62. Powley IR, Hughes MA, Cain K, MacFarlane M (2016) Caspase-8 tyrosine-380 phosphorylation inhibits CD95 DISC function by preventing procaspase-8 maturation and cycling within the complex. Oncogene 35:5629–5640CrossRefGoogle Scholar
  63. Rieser E, Cordier SM, Walczak H (2013) Linear ubiquitination: a newly discovered regulator of cell signalling. Trends Biochem Sci 38:94–102CrossRefGoogle Scholar
  64. Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak TW, Yagita H, Okumura K, Yeh WC, Nakano H (2001) Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death. J Biol Chem 276:36530–36534CrossRefGoogle Scholar
  65. Takahashi N, Duprez L, Grootjans S, Cauwels A, Nerinckx W, DuHadaway JB, Goossens V, Roelandt R, Van Hauwermeiren F, Libert C, Declercq W, Callewaert N, Prendergast GC, Degterev A, Yuan J, Vandenabeele P (2012) Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis 29:e437CrossRefGoogle Scholar
  66. Takahashi N, Vereecke L, Bertrand MJ, Duprez L, Berger SB, Divert T, Gonçalves A, Sze M, Gilbert B, Kourula S, Goossens V, Lefebvre S, Günther C, Becker C, Bertin J, Gough PJ, Declercq W, van Loo G, Vandenabeele P (2014) RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis. Nature 513:95–99CrossRefGoogle Scholar
  67. Tamiya H, Kim H, Klymenko O, Kim H, Feng Y, Zhang T, Han JY, Murao A, Snipas SJ, Jilaveanu L, Brown K, Kluger H, Zhang H, Iwai K, Ronai ZA (2018) SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth. J Clin Invest 128:517–530CrossRefGoogle Scholar
  68. Tang G, Minemoto Y, Dibling B, Purcell NH, Li Z, Karin M, Lin A (2001) Inhibition of JNK activation through NF-kappaB target genes. Nature 414:313–317CrossRefGoogle Scholar
  69. Tokunaga F, Iwai K (2012) LUBAC, a novel ubiquitin ligase for linear ubiquitination, is crucial for inflammation and immune responses. Microbes Infect 14:563–572CrossRefGoogle Scholar
  70. Tsuchiya Y, Nakabayashi O, Nakano H (2015) FLIP the switch: regulation of apoptosis and necroptosis by cFLIP. Int J Mol Sci 16:30321–30341CrossRefGoogle Scholar
  71. Tummers B, Green DR (2017) Caspase-8: regulating life and death. Immunol Rev 277:76–89CrossRefGoogle Scholar
  72. Vallabhapurapu S, Karin M (2009) Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 27:693–733CrossRefGoogle Scholar
  73. Vandenabeele P, Declercq W, Van Herreweghe F, Vanden Berghe T (2010) The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. Sci Signal 3:re4CrossRefGoogle Scholar
  74. Vanlangenakker N, Bertrand MJ, Bogaert P, Vandenabeele P, Vanden Berghe T (2011a) TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members. Cell Death Dis 17:e230CrossRefGoogle Scholar
  75. Vanlangenakker N, Vanden Berghe T, Bogaert P, Laukens B, Zobel K, Deshayes K, Vucic D, Fulda S, Vandenabeele P, Bertrand MJ (2011b) cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell Death Differ 18:656–665CrossRefGoogle Scholar
  76. Varfolomeev E, Vucic D (2008) (Un)expected roles of c-IAPs in apoptotic and NFkappaB signaling pathways. Cell Cycle 7:1511–1521CrossRefGoogle Scholar
  77. Varfolomeev E, Goncharov T, Fedorova AV, Dynek JN, Zobel K, Deshayes K, Fairbrother WJ, Vucic D (2008) c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J Biol Chem 283:24295–24299CrossRefGoogle Scholar
  78. Vlantis K, Wullaert A, Polykratis A, Kondylis V, Dannappel M, Schwarzer R, Welz P, Corona T, Walczak H, Weih F, Klein U, Kelliher M, Pasparakis M (2016) NEMO prevents RIP kinase 1-mediated epithelial cell death and chronic intestinal inflammation by NF-κB-dependent and -independent functions. Immunity 44:553–567CrossRefGoogle Scholar
  79. Wagner KW, Punnoose EA, Januario T, Lawrence DA, Pitti RM, Lancaster K, Lee D, von Goetz M, Yee SF, Totpal K, Huw L, Katta V, Cavet G, Hymowitz SG, Amler L, Ashkenazi A (2007) Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med 13:1070–1077CrossRefGoogle Scholar
  80. Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412:346–351CrossRefGoogle Scholar
  81. Wang L, Du F, Wang X (2008) TNF-α induces two distinct caspase-8 activation pathways. Cell 133:693–703CrossRefGoogle Scholar
  82. Weinlich R, Brunner T, Amarante-Mendes GP (2010) Control of death receptor ligand activity by posttranslational modifications. Cell Mol Life Sci 67:1631–1642CrossRefGoogle Scholar
  83. Won M, Park KA, Byun HS, Sohn KC, Kim YR, Jeon J, Hong JH, Park J, Seok JH, Kim JM, Yoon WH, Jang IS, Shen HM, Liu ZG, Hur GM (2010) Novel anti-apoptotic mechanism of A20 through targeting ASK1 to suppress TNF-induced JNK activation. Cell Death Differ 17:1830–1841CrossRefGoogle Scholar
  84. Won M, Byun HS, Park KA, Hur GM (2016) Post-translational control of NF-κB signaling by ubiquitination. Arch Pharm Res 39:1075–1084CrossRefGoogle Scholar
  85. Yin Q, Lamothe B, Darnay BG, Wu H (2009) Structural basis for the lack of E2 interaction in the RING domain of TRAF2. Biochemistry 48:10558–19567CrossRefGoogle Scholar
  86. Yoon HK, Byun HS, Lee H, Jeon J, Lee Y, Li Y, Jin EH, Kim J, Hong JH, Kim JH, Seok JH, Kang SW, Lee WH, Hur GM (2013) Intron-derived aberrant splicing of A20 transcript in rheumatoid arthritis. Rheumatology (Oxford) 52:427–437CrossRefGoogle Scholar
  87. Zhang L, Blackwell K, Shi Z, Habelhah H (2010) The RING domain of TRAF2 plays an essential role in the inhibition of TNFα-induced cell death but not in the activation of NF-κB. J Mol Biol 396:528–539CrossRefGoogle Scholar
  88. Zhang T, Park KA, Li Y, Byun HS, Jeon J, Lee Y, Hong JH, Kim JM, Huang SM, Choi SW, Kim SH, Sohn KC, Ro H, Lee JH, Lu T, Stark GR, Shen HM, Liu ZG, Park J, Hur GM (2013) PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65. Nat Commun 4:2062CrossRefGoogle Scholar
  89. Zhao Y, Ma CA, Wu L, Iwai K, Ashwell JD, Oltz EM, Ballard DW, Jain A (2015) CYLD and the NEMO zinc finger regulate tumor necrosis factor signaling and early embryogenesis. J Biol Chem 290:22076–22084CrossRefGoogle Scholar
  90. Zhao Q, Yu X, Zhang H, Liu Y, Zhang X, Wu X, Xie Q, Li M, Ying H, Zhang H (2017) RIPK3 mediates necroptosis during embryonic development and postnatal inflammation in FADD-deficient mice. Cell Rep 19:798–808CrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  • Kidong Kang
    • 1
  • So-Ra Lee
    • 1
  • Xuezhe Piao
    • 1
  • Gang Min Hur
    • 1
  1. 1.Department of Pharmacology and Department of Medical Science, College of MedicineChungnam National UniversityDaejeonRepublic of Korea

Personalised recommendations