Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1996 Nov 15;15(22):6189–6196.

RIP mediates tumor necrosis factor receptor 1 activation of NF-kappaB but not Fas/APO-1-initiated apoptosis.

A T Ting 1, F X Pimentel-Muiños 1, B Seed 1
PMCID: PMC452440  PMID: 8947041

Abstract

The CD95 (Fas/APO-1) and tumor necrosis factor (TNF) receptor pathways share many similarities, including a common reliance on proteins containing 'death domains' for elements of the membrane-proximal signal relay. We have created mutant cell lines that are unable to activate NF-kappaB in response to TNF. One of the mutant lines lacks RIP, a 74 kDa Ser/Thr kinase originally identified by its ability to associate with Fas/APO-1 and induce cell death. Reconstitution of the line with RIP restores responsiveness to TNF. The RIP-deficient cell line is susceptible to apoptosis initiated by anti-CD95 antibodies. An analysis of cells reconstituted with mutant forms of RIP reveals similarities between the action of RIP and FADD/MORT-1, a Fas-associated death domain protein.

Full text

PDF
6189

Images in this article

6191Image
on p.6191
6191Image
on p.6191
6193Image
on p.6193

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berberich I., Shu G. L., Clark E. A. Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. J Immunol. 1994 Nov 15;153(10):4357–4366. [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Cheng G., Baltimore D. TANK, a co-inducer with TRAF2 of TNF- and CD 40L-mediated NF-kappaB activation. Genes Dev. 1996 Apr 15;10(8):963–973. doi: 10.1101/gad.10.8.963. [DOI] [PubMed] [Google Scholar]
  5. Cheng G., Cleary A. M., Ye Z. S., Hong D. I., Lederman S., Baltimore D. Involvement of CRAF1, a relative of TRAF, in CD40 signaling. Science. 1995 Mar 10;267(5203):1494–1498. doi: 10.1126/science.7533327. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Chinnaiyan A. M., Tepper C. G., Seldin M. F., O'Rourke K., Kischkel F. C., Hellbardt S., Krammer P. H., Peter M. E., Dixit V. M. FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. J Biol Chem. 1996 Mar 1;271(9):4961–4965. doi: 10.1074/jbc.271.9.4961. [DOI] [PubMed] [Google Scholar]
  8. Clement M. V., Stamenkovic I. Fas and tumor necrosis factor receptor-mediated cell death: similarities and distinctions. J Exp Med. 1994 Aug 1;180(2):557–567. doi: 10.1084/jem.180.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Herrmann M., Lorenz H. M., Voll R., Grünke M., Woith W., Kalden J. R. A rapid and simple method for the isolation of apoptotic DNA fragments. Nucleic Acids Res. 1994 Dec 11;22(24):5506–5507. doi: 10.1093/nar/22.24.5506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hsu H., Huang J., Shu H. B., Baichwal V., Goeddel D. V. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity. 1996 Apr;4(4):387–396. doi: 10.1016/s1074-7613(00)80252-6. [DOI] [PubMed] [Google Scholar]
  11. Hsu H., Shu H. B., Pan M. G., Goeddel D. V. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell. 1996 Jan 26;84(2):299–308. doi: 10.1016/s0092-8674(00)80984-8. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Hu H. M., O'Rourke K., Boguski M. S., Dixit V. M. A novel RING finger protein interacts with the cytoplasmic domain of CD40. J Biol Chem. 1994 Dec 2;269(48):30069–30072. [PubMed] [Google Scholar]
  14. Kischkel F. C., Hellbardt S., Behrmann I., Germer M., Pawlita M., Krammer P. H., Peter M. E. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 1995 Nov 15;14(22):5579–5588. doi: 10.1002/j.1460-2075.1995.tb00245.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kohno T., Brewer M. T., Baker S. L., Schwartz P. E., King M. W., Hale K. K., Squires C. H., Thompson R. C., Vannice J. L. A second tumor necrosis factor receptor gene product can shed a naturally occurring tumor necrosis factor inhibitor. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8331–8335. doi: 10.1073/pnas.87.21.8331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Loetscher H., Pan Y. C., Lahm H. W., Gentz R., Brockhaus M., Tabuchi H., Lesslauer W. Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell. 1990 Apr 20;61(2):351–359. doi: 10.1016/0092-8674(90)90815-v. [DOI] [PubMed] [Google Scholar]
  17. Martin S. J., Reutelingsperger C. P., McGahon A. J., Rader J. A., van Schie R. C., LaFace D. M., Green D. R. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med. 1995 Nov 1;182(5):1545–1556. doi: 10.1084/jem.182.5.1545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McKendry R., John J., Flavell D., Müller M., Kerr I. M., Stark G. R. High-frequency mutagenesis of human cells and characterization of a mutant unresponsive to both alpha and gamma interferons. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11455–11459. doi: 10.1073/pnas.88.24.11455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mosialos G., Birkenbach M., Yalamanchili R., VanArsdale T., Ware C., Kieff E. The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell. 1995 Feb 10;80(3):389–399. doi: 10.1016/0092-8674(95)90489-1. [DOI] [PubMed] [Google Scholar]
  20. Rothe M., Pan M. G., Henzel W. J., Ayres T. M., Goeddel D. V. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell. 1995 Dec 29;83(7):1243–1252. doi: 10.1016/0092-8674(95)90149-3. [DOI] [PubMed] [Google Scholar]
  21. Rothe M., Sarma V., Dixit V. M., Goeddel D. V. TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40. Science. 1995 Sep 8;269(5229):1424–1427. doi: 10.1126/science.7544915. [DOI] [PubMed] [Google Scholar]
  22. Rothe M., Wong S. C., Henzel W. J., Goeddel D. V. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell. 1994 Aug 26;78(4):681–692. doi: 10.1016/0092-8674(94)90532-0. [DOI] [PubMed] [Google Scholar]
  23. Sato T., Irie S., Reed J. C. A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40. FEBS Lett. 1995 Jan 23;358(2):113–118. doi: 10.1016/0014-5793(94)01406-q. [DOI] [PubMed] [Google Scholar]
  24. Schattner E. J., Elkon K. B., Yoo D. H., Tumang J., Krammer P. H., Crow M. K., Friedman S. M. CD40 ligation induces Apo-1/Fas expression on human B lymphocytes and facilitates apoptosis through the Apo-1/Fas pathway. J Exp Med. 1995 Nov 1;182(5):1557–1565. doi: 10.1084/jem.182.5.1557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Smith C. A., Farrah T., Goodwin R. G. The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell. 1994 Mar 25;76(6):959–962. doi: 10.1016/0092-8674(94)90372-7. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Ting A. T., Karnitz L. M., Schoon R. A., Abraham R. T., Leibson P. J. Fc gamma receptor activation induces the tyrosine phosphorylation of both phospholipase C (PLC)-gamma 1 and PLC-gamma 2 in natural killer cells. J Exp Med. 1992 Dec 1;176(6):1751–1755. doi: 10.1084/jem.176.6.1751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Varfolomeev E. E., Boldin M. P., Goncharov T. M., Wallach D. 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. J Exp Med. 1996 Mar 1;183(3):1271–1275. doi: 10.1084/jem.183.3.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vermes I., Haanen C., Steffens-Nakken H., Reutelingsperger C. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods. 1995 Jul 17;184(1):39–51. doi: 10.1016/0022-1759(95)00072-i. [DOI] [PubMed] [Google Scholar]
  31. Zheng L., Fisher G., Miller R. E., Peschon J., Lynch D. H., Lenardo M. J. Induction of apoptosis in mature T cells by tumour necrosis factor. Nature. 1995 Sep 28;377(6547):348–351. doi: 10.1038/377348a0. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES