BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

E3 ubiquitin ligases and deubiquitinases as modulators of TRAIL-mediated extrinsic apoptotic signaling pathway

  • Woo, Seon Min (Department of Immunology, School of Medicine, Keimyung University) ;
  • Kwon, Taeg Kyu (Department of Immunology, School of Medicine, Keimyung University)
  • Received : 2018.11.19
  • Published : 2019.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) initiates the extrinsic apoptotic pathway through formation of the death-inducing signaling complex (DISC), followed by activation of effector caspases. TRAIL receptors are composed of death receptors (DR4 and DR5), decoy receptors (DcR1 and DcR2), and osteoprotegerin. Among them, only DRs activate apoptotic signaling by TRAIL. Since the levels of DR expressions are higher in cancer cells than in normal cells, TRAIL selectively activates apoptotic signaling pathway in cancer cells. However, multiple mechanisms, including down-regulation of DR expression and pro-apoptotic proteins, and up-regulation of anti-apoptotic proteins, make cancer cells TRAIL-resistant. Therefore, many researchers have investigated strategies to overcome TRAIL resistance. In this review, we focus on protein regulation in relation to extrinsic apoptotic signaling pathways via ubiquitination. The ubiquitin proteasome system (UPS) is an important process in control of protein degradation and stabilization, and regulates proliferation and apoptosis in cancer cells. The level of ubiquitination of proteins is determined by the balance of E3 ubiquitin ligases and deubiquitinases (DUBs), which determine protein stability. Regulation of the UPS may be an attractive target for enhancement of TRAIL-induced apoptosis. Our review provides insight to increasing sensitivity to TRAIL-mediated apoptosis through control of post-translational protein expression.

Keywords

References

  1. Hershko A and Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67, 425-479 https://doi.org/10.1146/annurev.biochem.67.1.425
  2. Pickart CM (2001) Mechanisms underlying ubiquitination. Annu Rev Biochem 70, 503-533 https://doi.org/10.1146/annurev.biochem.70.1.503
  3. Finley D, Ciechanover A and Varshavsky A (2004) Ubiquitin as a central cellular regulator. Cell 116, S29-32, 2 p following S32 https://doi.org/10.1016/S0092-8674(03)00971-1
  4. Ravid T and Hochstrasser M (2008) Diversity of degradation signals in the ubiquitin-proteasome system. Nat Rev Mol Cell Biol 9, 679-690 https://doi.org/10.1038/nrm2468
  5. Deshaies RJ and Joazeiro CA (2009) RING domain E3 ubiquitin ligases. Annu Rev Biochem 78, 399-434 https://doi.org/10.1146/annurev.biochem.78.101807.093809
  6. Joazeiro CA and Weissman AM (2000) RING finger proteins: mediators of ubiquitin ligase activity. Cell 102, 549-552 https://doi.org/10.1016/S0092-8674(00)00077-5
  7. Ikeda F and Dikic I (2008) Atypical ubiquitin chains: new molecular signals. 'Protein Modifications: Beyond the Usual Suspects' review series. EMBO Rep 9, 536-542 https://doi.org/10.1038/embor.2008.93
  8. Kulathu Y and Komander D (2012) Atypical ubiquitylation - the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages. Nat Rev Mol Cell Biol 13, 508-523 https://doi.org/10.1038/nrm3394
  9. Olzmann JA and Chin LS (2008) Parkin-mediated K63-linked polyubiquitination: a signal for targeting misfolded proteins to the aggresome-autophagy pathway. Autophagy 4, 85-87 https://doi.org/10.4161/auto.5172
  10. Shen M, Schmitt S, Buac D and Dou QP (2013) Targeting the ubiquitin-proteasome system for cancer therapy. Expert Opin Ther Targets 17, 1091-1108 https://doi.org/10.1517/14728222.2013.815728
  11. Ding F, Xiao H, Wang M, Xie X and Hu F (2014) The role of the ubiquitin-proteasome pathway in cancer development and treatment. Front Biosci (Landmark Ed) 19, 886-895 https://doi.org/10.2741/4254
  12. Orlowski RZ (1999) The role of the ubiquitin-proteasome pathway in apoptosis. Cell Death Differ 6, 303-313 https://doi.org/10.1038/sj.cdd.4400505
  13. Reyes-Turcu FE, Ventii KH and Wilkinson KD (2009) Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu Rev Biochem 78, 363-397 https://doi.org/10.1146/annurev.biochem.78.082307.091526
  14. Leznicki P and Kulathu Y (2017) Mechanisms of regulation and diversification of deubiquitylating enzyme function. J Cell Sci 130, 1997-2006 https://doi.org/10.1242/jcs.201855
  15. Nijman SM, Luna-Vargas MP, Velds A et al (2005) A genomic and functional inventory of deubiquitinating enzymes. Cell 123, 773-786 https://doi.org/10.1016/j.cell.2005.11.007
  16. Clague MJ, Barsukov I, Coulson JM, Liu H, Rigden DJ and Urbe S (2013) Deubiquitylases from genes to organism. Physiol Rev 93, 1289-1315 https://doi.org/10.1152/physrev.00002.2013
  17. Komander D, Clague MJ and Urbe S (2009) Breaking the chains: structure and function of the deubiquitinases. Nat Rev Mol Cell Biol 10, 550-563 https://doi.org/10.1038/nrm2731
  18. Abdul Rehman SA, Kristariyanto YA, Choi SY et al (2016) MINDY-1 is a member of an evolutionarily conserved and structurally distinct new family of deubiquitinating enzymes. Mol Cell 63, 146-155 https://doi.org/10.1016/j.molcel.2016.05.009
  19. Bielskiene K, Bagdoniene L, Mozuraitiene J, Kazbariene B and Janulionis E (2015) E3 ubiquitin ligases as drug targets and prognostic biomarkers in melanoma. Medicina (Kaunas) 51, 1-9 https://doi.org/10.1016/j.medici.2015.01.007
  20. D'Arcy P, Wang X and Linder S (2015) Deubiquitinase inhibition as a cancer therapeutic strategy. Pharmacol Ther 147, 32-54 https://doi.org/10.1016/j.pharmthera.2014.11.002
  21. Nicholson B, Marblestone JG, Butt TR and Mattern MR (2007) Deubiquitinating enzymes as novel anticancer targets. Future Oncol 3, 191-199 https://doi.org/10.2217/14796694.3.2.191
  22. Ashkenazi A, Pai RC, Fong S et al (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104, 155-162 https://doi.org/10.1172/JCI6926
  23. Walczak H, Miller RE, Ariail K et al (1999) Tumoricidal activity of tumor necrosis factor-related apoptosisinducing ligand in vivo. Nat Med 5, 157-163 https://doi.org/10.1038/5517
  24. Wang S and El-Deiry WS (2003) TRAIL and apoptosis induction by TNF-family death receptors. Oncogene 22, 8628-8633 https://doi.org/10.1038/sj.onc.1207232
  25. Pan G, O'Rourke K, Chinnaiyan AM et al (1997) The receptor for the cytotoxic ligand TRAIL. Science 276, 111-113 https://doi.org/10.1126/science.276.5309.111
  26. Sheridan JP, Marsters SA, Pitti RM et al (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277, 818-821 https://doi.org/10.1126/science.277.5327.818
  27. Srivastava RK (2001) TRAIL/Apo-2L: mechanisms and clinical applications in cancer. Neoplasia 3, 535-546 https://doi.org/10.1038/sj.neo.7900203
  28. Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ and Ashkenazi A (2000) Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 12, 611-620 https://doi.org/10.1016/S1074-7613(00)80212-5
  29. Kantari C and Walczak H (2011) Caspase-8 and bid: caught in the act between death receptors and mitochondria. Biochim Biophys Acta 1813, 558-563 https://doi.org/10.1016/j.bbamcr.2011.01.026
  30. Zhang L and Fang B (2005) Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther 12, 228-237 https://doi.org/10.1038/sj.cgt.7700792
  31. Jin Z, McDonald ER 3rd, Dicker DT and El-Deiry WS (2004) Deficient tumor necrosis factor-related apoptosisinducing ligand (TRAIL) death receptor transport to the cell surface in human colon cancer cells selected for resistance to TRAIL-induced apoptosis. J Biol Chem 279, 35829-35839 https://doi.org/10.1074/jbc.M405538200
  32. Zhang Y and Zhang B (2008) TRAIL resistance of breast cancer cells is associated with constitutive endocytosis of death receptors 4 and 5. Mol Cancer Res 6, 1861-1871 https://doi.org/10.1158/1541-7786.MCR-08-0313
  33. Song JJ, Szczepanski MJ, Kim SY et al (2010) c-Cbl-mediated degradation of TRAIL receptors is responsible for the development of the early phase of TRAIL resistance. Cell Signal 22, 553-563 https://doi.org/10.1016/j.cellsig.2009.11.012
  34. Kim SY, Kim JH and Song JJ (2013) c-Cbl shRNAexpressing adenovirus sensitizes TRAIL-induced apoptosis in prostate cancer DU-145 through increases of DR4/5. Cancer Gene Ther 20, 82-87 https://doi.org/10.1038/cgt.2012.88
  35. van de Kooij B, Verbrugge I, de Vries E et al (2013) Ubiquitination by the membrane-associated RING-CH-8 (MARCH-8) ligase controls steady-state cell surface expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor 1. J Biol Chem 288, 6617-6628 https://doi.org/10.1074/jbc.M112.448209
  36. Park EJ, Min KJ, Choi KS et al (2016) Chloroquine enhances TRAIL-mediated apoptosis through up-regulation of DR5 by stabilization of mRNA and protein in cancer cells. Sci Rep 6, 22921 https://doi.org/10.1038/srep22921
  37. D'Arcy P and Linder S (2012) Proteasome deubiquitinases as novel targets for cancer therapy. Int J Biochem Cell Biol 44, 1729-1738 https://doi.org/10.1016/j.biocel.2012.07.011
  38. D'Arcy P, Brnjic S, Olofsson MH et al (2011) Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nat Med 17, 1636-1640 https://doi.org/10.1038/nm.2536
  39. Oh YT, Deng L, Deng J and Sun SY (2017) The proteasome deubiquitinase inhibitor b-AP15 enhances DR5 activation-induced apoptosis through stabilizing DR5. Sci Rep 7, 8027 https://doi.org/10.1038/s41598-017-08424-w
  40. Oh YT, Qian G, Deng J and Sun SY (2018) Monocyte chemotactic protein-induced protein-1 enhances DR5 degradation and negatively regulates DR5 activationinduced apoptosis through its deubiquitinase function. Oncogene 37, 3415-3425 https://doi.org/10.1038/s41388-018-0200-9
  41. Jin Z, Li Y, Pitti R et al (2009) Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell 137, 721-735 https://doi.org/10.1016/j.cell.2009.03.015
  42. Bosu DR and Kipreos ET (2008) Cullin-RING ubiquitin ligases: global regulation and activation cycles. Cell Div 3, 7 https://doi.org/10.1186/1747-1028-3-7
  43. Petroski MD and Deshaies RJ (2005) Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 6, 9-20 https://doi.org/10.1038/nrm1547
  44. Gonzalvez F, Lawrence D, Yang B et al (2012) TRAF2 Sets a threshold for extrinsic apoptosis by tagging caspase-8 with a ubiquitin shutoff timer. Mol Cell 48, 888-899 https://doi.org/10.1016/j.molcel.2012.09.031
  45. Xu L, Zhang Y, Qu X et al (2017) DR5-Cbl-b/c-Cbl-TRAF2 complex inhibits TRAIL-induced apoptosis by promoting TRAF2-mediated polyubiquitination of caspase-8 in gastric cancer cells. Mol Oncol 11, 1733-1751 https://doi.org/10.1002/1878-0261.12140
  46. Li Y, Kong Y, Zhou Z et al (2013) The HECTD3 E3 ubiquitin ligase facilitates cancer cell survival by promoting K63-linked polyubiquitination of caspase-8. Cell Death Dis 4, e935 https://doi.org/10.1038/cddis.2013.464
  47. Zhou Z, Liu R and Chen C (2012) The WWP1 ubiquitin E3 ligase increases TRAIL resistance in breast cancer. Int J Cancer 130, 1504-1510 https://doi.org/10.1002/ijc.26122
  48. Christian PA, Fiandalo MV and Schwarze SR (2011) Possible role of death receptor-mediated apoptosis by the E3 ubiquitin ligases Siah2 and POSH. Mol Cancer 10, 57 https://doi.org/10.1186/1476-4598-10-57
  49. Bodmer JL, Holler N, Reynard S et al (2000) TRAIL receptor-2 signals apoptosis through FADD and caspase-8. Nat Cell Biol 2, 241-243 https://doi.org/10.1038/35008667
  50. Sprick MR, Weigand MA, Rieser E et al (2000) FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity 12, 599-609 https://doi.org/10.1016/S1074-7613(00)80211-3
  51. Lee EW, Kim JH, Ahn YH et al (2012) Ubiquitination and degradation of the FADD adaptor protein regulate death receptor-mediated apoptosis and necroptosis. Nat Commun 3, 978 https://doi.org/10.1038/ncomms1981
  52. Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J and Hood L (1997) Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway. Immunity 7, 821-830 https://doi.org/10.1016/S1074-7613(00)80400-8
  53. Hsu H, Shu HB, Pan MG and Goeddel DV (1996) TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84, 299-308 https://doi.org/10.1016/S0092-8674(00)80984-8
  54. Sessler T, Healy S, Samali A and Szegezdi E (2013) Structural determinants of DISC function: new insights into death receptor-mediated apoptosis signalling. Pharmacol Ther 140, 186-199 https://doi.org/10.1016/j.pharmthera.2013.06.009
  55. Christofferson DE, Li Y and Yuan J (2014) Control of life-or-death decisions by RIP1 kinase. Annu Rev Physiol 76, 129-150 https://doi.org/10.1146/annurev-physiol-021113-170259
  56. Wertz IE, O'Rourke KM, Zhou H et al (2004) De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 430, 694-699 https://doi.org/10.1038/nature02794
  57. Bellail AC, Olson JJ, Yang X, Chen ZJ and Hao C (2012) A20 ubiquitin ligase-mediated polyubiquitination of RIP1 inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma. Cancer Discov 2, 140-155 https://doi.org/10.1158/2159-8290.CD-11-0172
  58. Dong B, Lv G, Wang Q et al (2012) Targeting A20 enhances TRAIL-induced apoptosis in hepatocellular carcinoma cells. Biochem Biophys Res Commun 418, 433-438 https://doi.org/10.1016/j.bbrc.2012.01.056
  59. Lafont E, Kantari-Mimoun C, Draber P et al (2017) The linear ubiquitin chain assembly complex regulates TRAIL-induced gene activation and cell death. EMBO J 36, 1147-1166 https://doi.org/10.15252/embj.201695699
  60. Kirisako T, Kamei K, Murata S et al (2006) A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J 25, 4877-4887 https://doi.org/10.1038/sj.emboj.7601360
  61. Roth W and Reed JC (2004) FLIP protein and TRAIL-induced apoptosis. Vitam Horm 67, 189-206 https://doi.org/10.1016/S0083-6729(04)67011-7
  62. Shirley S and Micheau O (2013) Targeting c-FLIP in cancer. Cancer Lett 332, 141-150 https://doi.org/10.1016/j.canlet.2010.10.009
  63. Griffith TS, Chin WA, Jackson GC, Lynch DH and Kubin MZ (1998) Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. J Immunol 161, 2833-2840
  64. Xiao CW, Yan X, Li Y, Reddy SA and Tsang BK (2003) Resistance of human ovarian cancer cells to tumor necrosis factor alpha is a consequence of nuclear factor kappaB-mediated induction of Fas-associated death domain-like interleukin-1beta-converting enzyme-like inhibitory protein. Endocrinology 144, 623-630 https://doi.org/10.1210/en.2001-211024
  65. Zhang X, Jin TG, Yang H, DeWolf WC, Khosravi-Far R and Olumi AF (2004) Persistent c-FLIP(L) expression is necessary and sufficient to maintain resistance to tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in prostate cancer. Cancer Res 64, 7086-7091 https://doi.org/10.1158/0008-5472.CAN-04-1498
  66. Valnet-Rabier MB, Challier B, Thiebault S et al (2005) c-Flip protein expression in Burkitt's lymphomas is associated with a poor clinical outcome. Br J Haematol 128, 767-773 https://doi.org/10.1111/j.1365-2141.2005.05378.x
  67. Valente G, Manfroi F, Peracchio C et al (2006) cFLIP expression correlates with tumour progression and patient outcome in non-Hodgkin lymphomas of low grade of malignancy. Br J Haematol 132, 560-570 https://doi.org/10.1111/j.1365-2141.2005.05898.x
  68. Ullenhag GJ, Mukherjee A, Watson NF, Al-Attar AH, Scholefield JH and Durrant LG (2007) Overexpression of FLIPL is an independent marker of poor prognosis in colorectal cancer patients. Clin Cancer Res 13, 5070-5075 https://doi.org/10.1158/1078-0432.CCR-06-2547
  69. Chang L, Kamata H, Solinas G et al (2006) The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover. Cell 124, 601-613 https://doi.org/10.1016/j.cell.2006.01.021
  70. Yang F, Tay KH, Dong L et al (2010) Cystatin B inhibition of TRAIL-induced apoptosis is associated with the protection of FLIP(L) from degradation by the E3 ligase itch in human melanoma cells. Cell Death Differ 17, 1354-1367 https://doi.org/10.1038/cdd.2010.29
  71. Seo BR, Min KJ, Woo SM et al (2017) Inhibition of cathepsin s induces mitochondrial ros that sensitizes trail-mediated apoptosis through p53-Mediated Downregulation of Bcl-2 and c-FLIP. Antioxid Redox Signal 27, 215-233 https://doi.org/10.1089/ars.2016.6749
  72. Zhao L, Yue P, Khuri FR and Sun SY (2013) mTOR complex 2 is involved in regulation of Cbl-dependent c-FLIP degradation and sensitivity of TRAIL-induced apoptosis. Cancer Res 73, 1946-1957 https://doi.org/10.1158/0008-5472.CAN-12-3710
  73. Hsu TS, Mo ST, Hsu PN and Lai MZ (2018) c-FLIP is a target of the E3 ligase deltex1 in gastric cancer. Cell Death Dis 9, 135 https://doi.org/10.1038/s41419-017-0165-6
  74. Haimerl F, Erhardt A, Sass G and Tiegs G (2009) Down-regulation of the de-ubiquitinating enzyme ubiquitin-specific protease 2 contributes to tumor necrosis factor-alpha-induced hepatocyte survival. J Biol Chem 284, 495-504 https://doi.org/10.1074/jbc.M803533200
  75. Panner A, Crane CA, Weng C et al (2010) Ubiquitinspecific protease 8 links the PTEN-Akt-AIP4 pathway to the control of FLIPS stability and TRAIL sensitivity in glioblastoma multiforme. Cancer Res 70, 5046-5053 https://doi.org/10.1158/0008-5472.CAN-09-3979
  76. Jeong M, Lee EW, Seong D et al (2017) USP8 suppresses death receptor-mediated apoptosis by enhancing FLIPL stability. Oncogene 36, 458-470 https://doi.org/10.1038/onc.2016.215