Abstract
Tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines that promotes apoptosis. TRAIL induces apoptosis via death receptors (DR4 and DR5) in a wide variety of tumor cells but not in normal cells. The objectives of this study are to investigate the intracellular mechanisms by which TRAIL induces apoptosis. The death receptor Fas, upon ligand binding, trimerizes and recruits the adaptor protein FADD through the cytoplasmic death domain of Fas. FADD then binds and activates procaspase-8. It is unclear whether FADD is required for TRAIL-induced apoptosis. Here we show that the signaling complex of DR4/DR5 is assembled in response to TRAIL binding. FADD and caspase-8, but not caspase-10, are recruited to the receptor, and cells deficient in either FADD or caspase-8 blocked TRAIL-induced apoptosis. In addition, TRAIL initiates the activation of caspases, the loss of mitochondrial transmembrane potential (Δψm), the cleavage of BID, and the redistribution of mitochondrial cytochrome c. Treatment of Jurkat cells with cyclosporin A delayed TRAIL-induced Δψm, caspase-3 activation and apoptosis. Similarly, Overexpression of Bcl-2 or Bcl-XL delayed, but did not inhibit, TRAIL-induced Δψm and apoptosis. In contrast, XIAP, cowpox virus CrmA and baculovirus p35 inhibited TRAIL-induced apoptosis. These data suggest that death receptors (DR4 and DR5) and Fas receptors induced apoptosis through identical signaling pathway, and TRAIL-induced apoptosis via both mitochondrial-dependent and -independent pathways.
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References
Adams JM, Cory S . 1998 Science 281: 1322–1326
Ashkenazi A, Dixit VM . 1998 Science 281: 1305–1308
Bernardi P . 1999 Physiol. Rev. 79: 1127–1155
Bertin J, Mendrysa SM, LaCount DJ, Gaur S, Krebs JF, Armstrong RC, Tomaselli KJ, Friesen PD . 1996 J. Virol. 70: 6251–6259
Bodmer JL, Holler N, Reynard S, Vinciguerra P, Schneider P, Juo P, Blenis J, Tschopp J . 2000 Nat. Cell. Biol. 2: 241–243
Bordier C . 1981 J. Biol. Chem. 256: 1604–1607
Chinnaiyan AM, Prasad U, Shankar S, Hamstra DA, Shanaiah M, Chenevert TL, Ross BD, Rehemtulla A . 2000 Proc. Natl Acad. Sci. USA 97: 1754–1759
Clen RJ, Miller LK . 1994 Mol. Cell. Biol. 14: 5212–5222
Datta R, Kojima H, Banach D, Bump NJ, Talanian RV, Alnemri ES, Weichselbaum RR, Wong WW, Kufe DW . 1997 J. Biol. Chem. 272: 1965–1969
Decaudin D, Geley S, Hirsch T, Castedo M, Marchetti P, Macho A, Kofler R, Kroemer G . 1997 Cancer Res. 57: 62–67
Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG . 1997a Immunity 7: 813–820
Degli-Esposti MA, Smolak PJ, Walczak H, Waugh J, Huang CP, DuBose RF, Goodwin RG, Smith CA . 1997b J. Exp. Med. 186: 1165–1170
Deveraux QL, Reed JC . 1999 Genes Dev. 13: 239–252
Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC . 1998 EMBO J. 17: 2215–2223
Deveraux QL, Takahashi R, Salvesen GS, Reed JC . 1997 Nature 388: 300–304
Duckett CS, Nava VE, Gedrich RW, Clem RJ, Van Dongen JL, Gilfillan MC, Shiels H, Hardwick JM, Thompson CB . 1996 EMBO J. 15: 2685–2694
Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR . 1998 J. Biol. Chem. 273: 14363–14367
Enari M . 2000 Seikagaku 72: 6–15
French LE, Tschopp J . 1999 Nat. Med. 5: 146–147
Gibson SB, Oyer R, Spalding AC, Anderson SM, Johnson GL . 2000 Mol. Cell. Biol. 20: 205–212
Golstein P . 1997 Curr. Biol. 7: R750–R753
Green DR . 1998 Cell 94: 695–698
Green DR, Reed JC . 1998 Science 281: 1309–1312
Griffith TS, Chin WA, Jackson GC, Lynch DH, Kubin MZ . 1998 J. Immunol. 161: 2833–2840
Griffith TS, Lynch DH . 1998 Curr. Opin. Immunol. 10: 559–563
Gross A, Yin XM, Wang K, Wei MC, Jockel J, Milliman C, Erdjument-Bromage H, Tempst P, Korsmeyer SJ . 1999 J. Biol. Chem. 274: 1156–1163
Gura T . 1997 Science 277: 768
Han Z, Bhalla K, Pantazis P, Hendrickson EA, Wyche JH . 1999 Mol. Cell. Biol. 19: 1381–1389
Hay BA, Wolff T, Rubin GM . 1994 Development 120: 2121–2129
He L, Poblenz AT, Medrano CJ, Fox DA . 2000 J. Biol. Chem. 275: 12175–12184
Ichas F, Mazat JP . 1998 Biochim. Biophys. Acta 1366: 33–50
Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J . 1997 Nature 388: 190–195
Juo P, Kuo CJ, Yuan J, Blenis J . 1998 Curr. Biol. 8: 1001–1008
Juo P, Woo MS, Kuo CJ, Signorelli P, Biemann HP, Hannun YA, Blenis J . 1999 Cell Growth Differ. 10: 797–804
Kasibhatla S, Brunner T, Genestier L, Echeverri F, Mahboubi A, Green DR . 1998 Mol. Cell. 1: 543–551
Keogh SA, Walczak H, Bouchier-Hayes L, Martin SJ . 2000 FEBS Lett. 471: 93–98
Kim EJ, Suliman A, Lam A, Srivastava RK . 2001 Int. J. Oncology 18: 187–194
Kim K, Fisher MJ, Xu SQ, el-Deiry WS . 2000 Clin. Cancer Res. 6: 335–346
Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A . 2000 Immunity 12: 611–620
Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD . 1997 Science 275: 1132–1136
Korsmeyer SJ . 1999 Cancer Res. 59: 1693s–1700s
Krammer PH . 1999 Adv. Immunol. 71: 163–210
Kroemer G, Dallaporta B, Resche-Rigon M . 1998 Annu. Rev. Physiol. 60: 619–642
LaCasse EC, Baird S, Korneluk RG, MacKenzie AE . 1998 Oncogene 17: 3247–3259
Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG, Earnshaw WC . 1994 Nature 371: 346–347
Li H, Kolluri SK, Gu J, Dawson MI, Cao X, Hobbs PD, Lin B, Chen G, Lu J, Lin F, Xie Z, Fontana JA, Reed JC, Zhang X . 2000 Science 289: 1159–1164
Li H, Zhu H, Xu CJ, Yuan J . 1998 Cell 94: 491–501
Liston P, Roy N, Tamai K, Lefebvre C, Baird S, Cherton-Horvat G, Farahani R, McLean M, Ikeda JE, MacKenzie A, Korneluk RG . 1996 Nature 379: 349–353
Luo X, Budihardjo I, Zou H, Slaughter C, Wang X . 1998 Cell 94: 481–490
Marsters SA, Sheridan JP, Pitti RM, Huang A, Skubatch M, Baldwin D, Yuan J, Gurney A, Goddard AD, Godowski P, Ashkenazi A . 1997 Curr. Biol. 7: 1003–1006
Martin SJ, Green DR . 1995 Cell 82: 349–352
Miller LK . 1999 Trends Cell. Biol. 9: 323–328
Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA. et al . 1995 Nature 376: 37–43
Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM . 1997a Science 277: 815–818
Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM . 1997b Science 276: 111–113
Peter ME, Krammer PH . 1998 Curr. Opin. Immunol. 10: 545–551
Peter ME, Scaffidi C, Medema JP, Kischkel F, Krammer PH . 1999 Res. Prob. Cell Differ. 23: 25–63
Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A . 1996 J. Biol. Chem. 271: 12687–12690
Rothe M, Pan MG, Henzel WJ, Ayres TM, Goeddel DV . 1995 Cell 83: 1243–1252
Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC . 1997 EMBO J. 16: 6914–6925
Salvesen GS . 1999 Apmis 107: 73–79
Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH, Peter ME . 1998 EMBO J. 17: 1675–1687
Schneider P, Bodmer JL, Thome M, Hofmann K, Holler N, Tschopp J . 1997a FEBS Lett. 416: 329–334
Schneider P, Thome M, Burns K, Bodmer JL, Hofmann K, Kataoka T, Holler N, Tschopp J . 1997b Immunity 7: 831–836
Schulze-Osthoff K, Ferrari D, Los M, Wesselborg S, Peter ME . 1998 Eur. J. Biochem. 254: 439–459
Screaton GR, Mongkolsapaya J, Xu XN, Cowper AE, McMichael AJ, Bell JI . 1997 Curr. Biol. 7: 693–696
Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A . 1997 Science 277: 818–821
Simonian PL, Grillot DA, Nunez G . 1997 Blood 90: 1208–1216
Sprick MR, Weigand MA, Rieser E, Rauch CT, Juo P, Blenis J, Krammer PH, Walczak H . 2000 Immunity 12: 599–609
Srivastava RK, Mi QS, Hardwick JM, Longo DL . 1999a Proc. Natl. Acad. Sci. USA 96: 3775–3780
Srivastava RK, Sasaki CY, Hardwick JM, Longo DL . 1999b J. Exp. Med. 190: 253–265
Srivastava RK, Sollott SJ, Khan L, Hansford R, Lakatta EG, Longo DL . 1999c Mol. Cell. Biol. 19: 5659–5674
Srivastava RK, Srivastava AR, Cho-Chung YS, Longo DL . 1999d Oncogene 18: 1755–1763
Susin SA, Zamzami N, Kroemer G . 1998 Biochim. Biophys. Acta. 1366: 151–165
Tanaka M, Suda T, Yatomi T, Nakamura N, Nagata S . 1997 J. Immunol. 158: 2303–2309
Tewari M, Beidler DR, Dixit VM . 1995a J. Biol. Chem. 270: 18738–18741
Tewari M, Telford WG, Miller RA, Dixit VM . 1995b J. Biol. Chem. 270: 22705–22708
Uren AG, Pakusch M, Hawkins CJ, Puls KL, Vaux DL . 1996 Proc. Natl. Acad. Sci. USA 93: 4974–4978
Wajant H, Johannes FJ, Haas E, Siemienski K, Schwenzer R, Schubert G, Weiss T, Grell M, Scheurich P . 1998 Curr. Biol. 8: 113–116
Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT . 1997 EMBO J. 16: 5386–5397
Walczak H, Krammer PH . 2000 Exp. Cell. Res. 256: 58–66
Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC, Lynch DH . 1999 Nat. Med. 5: 157–163
Wang J, Zheng L, Lobito A, Chan FK, Dale J, Sneller M, Yao X, Puck JM, Straus SE, Lenardo MJ . 1999 Cell 98: 47–58
Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA . 1995 Immunity 3: 673–682
Wolf BB, Goldstein JC, Stennicke HR, Beere H, Amarante-Mendes GP, Salvesen GS, Green DR . 1999 Blood 94: 1683–1692
Wu GS, Burns TF, McDonald III ER, Jiang W, Meng R, Krantz ID, Kao G, Gan DD, Zhou JY, Muschel R, Hamilton SR, Spinner NB, Markowitz S, Wu G, el-Deiry WS . 1997 Nat. Genet. 17: 141–143
Yeh WC, Pompa JL, McCurrach ME, Shu HB, Elia AJ, Shahinian A, Ng M, Wakeham A, Khoo W, Mitchell K, El-Deiry WS, Lowe SW, Goeddel DV, Mak TW . 1998 Science 279: 1954–1958
Acknowledgements
We extend our sincere thanks to Craig Thompson (University of Pennsylvania, Philadelphia, PA, USA) and Stanley Korsmeyer (Dana-Farber Cancer Institute, Boston, MA, USA) for providing the Bcl-XL and Bcl-2 expression vector, respectively. We are grateful to Dr John Blennis (Harvard Medical School, Boston, MA, USA) for providing caspase-8 and FADD deficient Jurkat cells. We also thank Dr Vishva Dixit (Genentech, South San Francisco, CA, USA) for providing dominant negative FADD and caspase-8 constructs.
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Suliman, A., Lam, A., Datta, R. et al. Intracellular mechanisms of TRAIL: apoptosis through mitochondrial-dependent and -independent pathways. Oncogene 20, 2122–2133 (2001). https://doi.org/10.1038/sj.onc.1204282
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DOI: https://doi.org/10.1038/sj.onc.1204282
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