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Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1)

Oncogene volume 18, pages 5814–5820 (1999)Cite this article

Abstract

Tumor necrosis factor-α (TNF), a major inflammatory cytokine, generates a wide variety of cellular responses via key cytoplasmic adaptor molecules named TNF receptor-associated factors (TRAFs). We report that TRAF2, TRAF5 and TRAF6 associate with apoptosis signal-regulating kinase 1 (ASK1), and a catalytically-inactive ASK1 mutant blocks stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) activation by these TRAFs. A truncated derivative of TRAF2, which inhibits SAPK activation by TNF, blocks TNF-induced ASK1 activation. Furthermore, protection from TNF-induced cell death conferred by an ASK1 mutant is dependent upon TRAF2. Hence, ASK1 is a common mediator of TRAF-regulated SAPK and apoptosis signaling, and the TRAF2 – ASK1 connection completes the signaling cascade from TNF to SAPK/JNK activation.

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References

  • Adler V, Polotskaya A, Wagner F and Kraft AS. . 1992 J. Biol. Chem. 267: 17001–17005.

  • Arch RH, Gedrich RW and Thompson CB. . 1998 Genes Dev. 12: 2821–2830.

  • Cao Z, Xiong J, Takeuchi M, Kurama T and Goeddel DV. . 1996 Nature 383: 443–446.

  • Cardone MH, Salvesen GS, Widmann C, Johnson G and Frisch SM. . 1997 Cell 90: 315–323.

  • Chang HY, Nishitoh H, Yang X, Ichijo H and Baltimore D. . 1998 Science 281: 1860–1863.

  • Cheng G, Cleary AM, Ye ZS, Hong DI, Lederman S and Baltimore D. . 1995 Science 267: 1494–1498.

  • Frisch SM, Vuori K, Kelaita D and Sicks S. . 1996 J. Cell. Biol. 135: 1377–1382.

  • Gotoh Y and Cooper JA. . 1998 J. Biol. Chem. 273: 17477–17482.

  • Gruss HJ. . 1996 Int. J. Clin. Lab. Res. 26: 143–159.

  • Holland PM, Suzanne M, Campbell JS, Noselli S and Cooper JA. . 1997 J. Biol. Chem. 272: 24994–24998.

  • Hsu H, Huang J, Shu HB, Baichwal V and Goeddel DV. . 1996a Immunity 4: 387–396.

  • Hus H, Shu HB, Pan MG and Goeddel DV. . 1996b Cell 84: 299–308.

  • Hsu H, Xiong J and Goeddel DV. . 1995 Cell 81: 495–504.

  • Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, Takagi M, Matsumoto K, Miyazono K and Gotoh Y. . 1997 Science 275: 90–94.

  • Ishida T, Mizushima S, Azuma S, Kobayashi N, Tojo T, Suzuki K, Aizawa S, Watanabe T, Mosialos G, Kieff E, Yamamoto T and Inoue J. . 1996a J. Biol. Chem. 271: 28745–28748.

  • Ishida TK, Tojo T, Aoki T, Kobayashi N, Ohishi T, Watanabe T, Yamamoto T and Inoue J. . 1996b Proc. Natl. Acad. Sci. USA 93: 9437–9442.

  • Karin M and Delhase M. . 1998 Proc. Natl. Acad. Sci. USA 95: 9067–9069.

  • Kiefer F, Tibbles LA, Lassam N, Zanke B, Iscove N and Woodgett JR. . 1997 Biochem. Soc. Trans. 25: 491–498.

  • Kumar S, Kinoshita M, Noda M, Copeland NG and Jenkins NA. . 1994 Genes Dev 8: 1613–1626.

  • Kyriakis JM, Banerjee P, Nikolakaki E, Dai T, Rubie EA, Ahmad MF, Avruch J and Woodgett JR. . 1994 Nature 369: 156–160.

  • LaCasse EC, Baird S, Korneluk RG and MacKenzie AE. . 1998 Oncogene 17: 3247–3259.

  • Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL and Karin M. . 1995 Science 268: 286–290.

  • Malinin NL, Boldin MP, Kovalenko AV and Wallach D. . 1997 Nature 385: 540–544.

  • Moriguchi T, Toyoshima F, Masuyama N, Hanafusa H, Gotoh Y and Nishida E. . 1997 EMBO J. 16: 7045–7053.

  • Nagata S. . 1997 Cell 88: 355–365.

  • Naismith JH and Sprang SR. . 1998 Trends Biochem. Sci. 23: 74–79.

  • Natoli G, Costanzo A, Moretti F, Fulco M, Balsano C and Levrero M. . 1997 J. Biol. Chem. 272: 26079–26082.

  • Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, Miyazono K and Ichijo H. . 1998 Mol. Cell 2: 389–395.

  • Park DS, Stefanis L, Yan CY, Farinelli SE and Greene LA. . 1996 J. Biol. Chem. 271: 21898–21905.

  • Pombo CM, Kehrl JH, Sanchez I, Katz P, Avruch J, Zon LI, Woodgett JR, Force T and Kyriakis JM. . 1995 Nature 377: 750–754.

  • Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E and Woodgett JR. . 1991 Nature 353: 670–674.

  • Regnier CH, Tomasetto C, Moog-Lutz C, Chenard MP, Wendling C, Basset P and Rio MC. . 1995 J. Biol. Chem. 270: 25715–25721.

  • Rothe M, Pan MG, Henzel WJ, Ayres TM and Goeddel DV. . 1995 Cell 83: 1243–1252.

  • Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, Kawabata M, Miyazono K and Ichijo H. . 1998 EMBO J. 17: 2596–2606.

  • Sanchez I, Hughes RT, Mayer BJ, Yee K, Woodgett JR, Avruch J, Kyriakis JM and Zon LI. . 1994 Nature 372: 794–798.

  • Smith CA, Farrah T and Goodwin RG. . 1994 Cell 76: 959–962.

  • Song HY, Regnier CH, Kirschning CJ, Goeddel DV and Rothe M. . 1997 Proc. Natl. Acad. Sci. USA 94: 9792–9796.

  • Takeuchi M, Rothe M and Goeddel DV. . 1996 J. Biol. Chem. 271: 19935–19942.

  • Tartaglia LA and Goeddel DV. . 1992 Immunol Today 13: 151–153.

  • Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T and Davis RJ. . 1997 Proc. Natl. Acad. Sci. USA 94: 7337–7342.

  • Wang XS, Diener K, Jannuzzi D, Trollinger D, Tan TH, Lichenstein H, Zukowski M and Yao Z. . 1996 J. Biol. Chem. 271: 31607–31611.

  • Widmann C, Gerwins P, Johnson NL, Jarpe MB and Johnson GL. . 1998 Mol. Cell. Biol. 18: 2416–2429.

  • Yan M, Dai T, Deak JC, Kyriakis JM, Zon LI, Woodgett JR and Templeton DJ. . 1994 Nature 372: 798–800.

  • Yao Z, Diener K, Wang XS, Zukowski M, Matsumoto G, Zhou G, Mo R, Sasaki T, Nishina H, Hui CC, Tan TH, Woodgett JP and Penninger JM. . 1997 J. Biol. Chem. 272: 32378–32383.

  • Yeh WC, Shahinian A, Speiser D, Kraunus J, Billia E, Wakeham A, de la Pompa JL, Ferrick D, Hum B, Iscove N, Ohashi P, Rothe M, Goeddel DV and Mak TW. . 1997 Immunity 7: 715–725.

  • Yuasa T, Ohno S, Kehrl JH and Kyriakis JM. . 1998 J. Biol. Chem. 273: 22681–22692.

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Acknowledgements

We thank Mike Rothe and Robert Korneluk for providing valuable reagents, and Si Tuen Lee, Jim Dimitroulakos and Elizabeth Rubie for helpful discussions and technical assistance. KP Hoeflich is supported by a Medical Research Council of Canada Studentship. JR Woodgett is supported by grants from the National Cancer Institute of Canada and Medical Research Council and is a Medical Research Council Senior Scientist.

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Authors and Affiliations

  1. Department of Medical Biophysics, Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada

    Klaus P Hoeflich, Wen-Chen Yeh, Tak W Mak & James R Woodgett

  2. Amgen Institute, Ontario Cancer Institute, 620 University Avenue, Toronto, Ontario, M5G 2C1, Canada

    Wen-Chen Yeh & Tak W Mak

  3. Amgen Inc., Boulder, 80301, Colorado, CO, USA

    Zhengbin Yao

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  1. Klaus P Hoeflich
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Hoeflich, K., Yeh, WC., Yao, Z. et al. Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1). Oncogene 18, 5814–5820 (1999). https://doi.org/10.1038/sj.onc.1202975

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