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. 1996 Mar 1;183(3):1271–1275. doi: 10.1084/jem.183.3.1271

A potential mechanism of "cross-talk" between the p55 tumor necrosis factor receptor and Fas/APO1: proteins binding to the death domains of the two receptors also bind to each other

PMCID: PMC2192337  PMID: 8642271

Abstract

The p55 tumor necrosis factor (TNF) receptor and Fas/APO1 induce cell death via distinct regions in their intracellular domains. Three cytoplasmic proteins that bind to these receptor regions have been identified recently. One, MORT1 (also called FADD), binds to Fas/APO1 but not to p55-R; another, TRADD, binds to the p55 TNF receptor but not to Fas/APO1; and the third, RIP, binds weakly to both receptors. The regions within these proteins that are involved in binding to the receptors and the receptor regions to which they bind share a common sequence motif, that of the "death domain." This study shows that the death domain motifs in MORT1, TRADD, and RIP bind effectively to each other, a mode of binding that may allow "cross-talk" between the functional expression of the p55 TNF receptor and Fas/APO1.

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Selected References

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  1. Bartel P., Chien C. T., Sternglanz R., Fields S. Elimination of false positives that arise in using the two-hybrid system. Biotechniques. 1993 Jun;14(6):920–924. [PubMed] [Google Scholar]
  2. Beutler B., Cerami A. Tumor necrosis, cachexia, shock, and inflammation: a common mediator. Annu Rev Biochem. 1988;57:505–518. doi: 10.1146/annurev.bi.57.070188.002445. [DOI] [PubMed] [Google Scholar]
  3. Bigda J., Beletsky I., Brakebusch C., Varfolomeev Y., Engelmann H., Bigda J., Holtmann H., Wallach D. Dual role of the p75 tumor necrosis factor (TNF) receptor in TNF cytotoxicity. J Exp Med. 1994 Aug 1;180(2):445–460. doi: 10.1084/jem.180.2.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boldin M. P., Mett I. L., Varfolomeev E. E., Chumakov I., Shemer-Avni Y., Camonis J. H., Wallach D. Self-association of the "death domains" of the p55 tumor necrosis factor (TNF) receptor and Fas/APO1 prompts signaling for TNF and Fas/APO1 effects. J Biol Chem. 1995 Jan 6;270(1):387–391. doi: 10.1074/jbc.270.1.387. [DOI] [PubMed] [Google Scholar]
  5. Boldin M. P., Varfolomeev E. E., Pancer Z., Mett I. L., Camonis J. H., Wallach D. A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain. J Biol Chem. 1995 Apr 7;270(14):7795–7798. doi: 10.1074/jbc.270.14.7795. [DOI] [PubMed] [Google Scholar]
  6. Brakebusch C., Nophar Y., Kemper O., Engelmann H., Wallach D. Cytoplasmic truncation of the p55 tumour necrosis factor (TNF) receptor abolishes signalling, but not induced shedding of the receptor. EMBO J. 1992 Mar;11(3):943–950. doi: 10.1002/j.1460-2075.1992.tb05133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chant J., Stowers L. GTPase cascades choreographing cellular behavior: movement, morphogenesis, and more. Cell. 1995 Apr 7;81(1):1–4. doi: 10.1016/0092-8674(95)90363-1. [DOI] [PubMed] [Google Scholar]
  8. Chinnaiyan A. M., O'Rourke K., Tewari M., Dixit V. M. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell. 1995 May 19;81(4):505–512. doi: 10.1016/0092-8674(95)90071-3. [DOI] [PubMed] [Google Scholar]
  9. Cleveland J. L., Ihle J. N. Contenders in FasL/TNF death signaling. Cell. 1995 May 19;81(4):479–482. doi: 10.1016/0092-8674(95)90068-3. [DOI] [PubMed] [Google Scholar]
  10. Enari M., Hug H., Nagata S. Involvement of an ICE-like protease in Fas-mediated apoptosis. Nature. 1995 May 4;375(6526):78–81. doi: 10.1038/375078a0. [DOI] [PubMed] [Google Scholar]
  11. Field J., Nikawa J., Broek D., MacDonald B., Rodgers L., Wilson I. A., Lerner R. A., Wigler M. Purification of a RAS-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method. Mol Cell Biol. 1988 May;8(5):2159–2165. doi: 10.1128/mcb.8.5.2159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grell M., Krammer P. H., Scheurich P. Segregation of APO-1/Fas antigen- and tumor necrosis factor receptor-mediated apoptosis. Eur J Immunol. 1994 Oct;24(10):2563–2566. doi: 10.1002/eji.1830241045. [DOI] [PubMed] [Google Scholar]
  13. Hennet T., Bertoni G., Richter C., Peterhans E. Expression of BCL-2 protein enhances the survival of mouse fibrosarcoid cells in tumor necrosis factor-mediated cytotoxicity. Cancer Res. 1993 Mar 15;53(6):1456–1460. [PubMed] [Google Scholar]
  14. Hsu H., Xiong J., Goeddel D. V. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell. 1995 May 19;81(4):495–504. doi: 10.1016/0092-8674(95)90070-5. [DOI] [PubMed] [Google Scholar]
  15. Itoh N., Nagata S. A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen. J Biol Chem. 1993 May 25;268(15):10932–10937. [PubMed] [Google Scholar]
  16. Itoh N., Tsujimoto Y., Nagata S. Effect of bcl-2 on Fas antigen-mediated cell death. J Immunol. 1993 Jul 15;151(2):621–627. [PubMed] [Google Scholar]
  17. Los M., Van de Craen M., Penning L. C., Schenk H., Westendorp M., Baeuerle P. A., Dröge W., Krammer P. H., Fiers W., Schulze-Osthoff K. Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis. Nature. 1995 May 4;375(6526):81–83. doi: 10.1038/375081a0. [DOI] [PubMed] [Google Scholar]
  18. Nagata S., Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. doi: 10.1126/science.7533326. [DOI] [PubMed] [Google Scholar]
  19. Schulze-Osthoff K., Krammer P. H., Dröge W. Divergent signalling via APO-1/Fas and the TNF receptor, two homologous molecules involved in physiological cell death. EMBO J. 1994 Oct 3;13(19):4587–4596. doi: 10.1002/j.1460-2075.1994.tb06780.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stanger B. Z., Leder P., Lee T. H., Kim E., Seed B. RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell. 1995 May 19;81(4):513–523. doi: 10.1016/0092-8674(95)90072-1. [DOI] [PubMed] [Google Scholar]
  21. Tartaglia L. A., Ayres T. M., Wong G. H., Goeddel D. V. A novel domain within the 55 kd TNF receptor signals cell death. Cell. 1993 Sep 10;74(5):845–853. doi: 10.1016/0092-8674(93)90464-2. [DOI] [PubMed] [Google Scholar]
  22. Tewari M., Dixit V. M. Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product. J Biol Chem. 1995 Feb 17;270(7):3255–3260. doi: 10.1074/jbc.270.7.3255. [DOI] [PubMed] [Google Scholar]
  23. Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol. 1992;10:411–452. doi: 10.1146/annurev.iy.10.040192.002211. [DOI] [PubMed] [Google Scholar]
  24. Watanabe-Fukunaga R., Brannan C. I., Copeland N. G., Jenkins N. A., Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992 Mar 26;356(6367):314–317. doi: 10.1038/356314a0. [DOI] [PubMed] [Google Scholar]
  25. Wong G. H., Goeddel D. V. Fas antigen and p55 TNF receptor signal apoptosis through distinct pathways. J Immunol. 1994 Feb 15;152(4):1751–1755. [PubMed] [Google Scholar]

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