Abstract
Death Effector Domains (DEDs) have been known to mediate the recruitment of Caspase 8 and its homologs to the aggregated death-inducing signaling complex (DISC), consisting of the death domain (DD)-containing receptors and various signaling proteins. In addition, several viruses were recently shown to encode proteins with DEDs (also called FLICE inhibitory proteins or vFLIPs) which have the ability of blocking cell death induced by DD-containing receptors. We provide evidence that vFLIPs can also modulate the NF-κB pathway and physically interact with several signaling proteins, such as the TRAFs, RIP, NIK and the IKKs. Modulation of the NF-κB pathway may play a role in the natural history of infection by these viruses.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Baeuerle PA and Baichwal VR. . 1997 Adv. Immunol. 65: 111–137.
Beauparlant P and Hiscott J. . 1996 Cytokine Growth Factor Rev. 7: 175–190.
Beg AA and Baltimore D. . 1996 Science 274: 782–784.
Berberich I, Shu GL and Clark EA. . 1994 J. Immunol. 153: 4357–4366.
Bertin J, Armstrong RC, Ottilie S, Martin DA, Wang Y, Banks S, Wang GH, Senkevich TG, Alnemri ES, Moss B, Lenardo MJ, Tomaselli KJ and Cohen JI. . 1997 Proc. Natl. Acad. Sci. USA 94: 1172–1176.
Birthistle K and Carrington D. . 1997 J. Infect. 34: 21–28.
Boldin MP, Goncharov TM, Goltsev YV and Wallach D. . 1996 Cell 85: 803–815.
Boldin MP, Varfolomeev EE, Pancer Z, Mett IL, Camonis JH and Wallach D. . 1995 J. Biol. Chem. 270: 7795–7798.
Brockman JA, Scherer DC, McKinsey TA, Hall SM, Qi X, Lee WY and Ballard DW. . 1995 Mol. Cell. Biol. 15: 2809–2818.
Brooks LA, Wilson AJ and Crook T. . 1997 J. Pathol. 182: 262–265.
Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J and Hood L. . 1997 Immunity 7: 821–830.
Cheng G and Baltimore D. . 1996 Genes Dev. 10: 963–973.
Chinnaiyan AM, O'Rourke K, Tewari M and Dixit VM. . 1995 Cell 81: 505–512.
Chinnaiyan AM, Tepper CG, Seldin MF, O'Rourke K, Kischkel FC, Hellbardt S, Krammer PH, Peter ME and Dixit VM. . 1996 J. Biol. Chem. 271: 4961–4965.
DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E and Karin M. . 1997 Nature 388: 548–554.
Fernandes-Alnemri T, Armstrong RC, Krebs J, Srinivasula SM, Wang L, Bullrich F, Fritz LC, Trapani JA, Tomaselli KJ, Litwack G and Alnemri ES. . 1996 Proc. Natl. Acad. Sci. USA 93: 7464–7469.
Gallo RC. . 1998 J. Natl. Cancer Inst. Monogr. 23: 55–57.
Gilmore TD, Koedood M, Piffat KA and White DW. . 1996 Oncogene 13: 1367–1378.
Goltsev YV, Kovalenko AV, Arnold E, Varfolomeev EE, Brodianskii VM and Wallach D. . 1997 J. Biol. Chem. 272: 19641–19644.
Grimm S, Bauer MK, Baeuerle PA and Schulze-Osthoff K. . 1996 J. Cell. Biol. 134: 13–23.
Han DK, Chaudhary PM, Wright ME, Friedman C, Trask BJ, Riedel RT, Baskin DG, Schwartz SM and Hood L. . 1997 Proc. Natl. Acad. Sci. USA 94: 11333–11338.
Hettmann T, DiDonato J, Karin M and Leiden JM. . 1999 J. Exp. Med. 189: 145–158.
Hsu H, Huang J, Shu HB, Baichwal V and Goeddel DV. . 1996a Immunity 4: 387–396.
Hsu 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.
Hu S, Vincenz C, Buller M and Dixit VM. . 1997a J. Biol. Chem. 272: 9621–9624.
Hu S, Vincenz C, Ni J, Gentz R and Dixit VM. . 1997b J. Biol. Chem. 272: 17255–17257.
Inohara N, Koseki T, Hu Y, Chen S and Nunez G. . 1997 Proc. Natl. Acad. Sci. USA 94: 10717–10722.
Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE and Tschopp J. . 1997 Nature 388: 190–195.
Jung M, Zhang Y, Lee S and Dritschilo A. . 1995 Science 268: 1619–1621.
Karp JE, Pluda JM and Yarchoan R. . 1996 Hematol Oncol. Clin. North Am. 10: 1031–1049.
Liu ZG, Hsu H, Goeddel DV and Karin M. . 1996 Cell. 87: 565–576.
Malinin NL, Boldin MP, Kovalenko AV and Wallach D. . 1997 Nature 385: 540–544.
Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M, Manning A and Rao A. . 1997 Science 278: 860–866.
Miles SA. . 1996 Hematol Oncol. Clin. North Am. 10: 1011–1021.
Moore PS, Boshoff C, Weiss RA and Chang Y. . 1996 Science 274: 1739–1744.
Mosialos G. . 1997 Semin. Cancer Biol. 8: 121–129.
Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME and Dixit VM. . 1996 Cell 85: 817–827.
Nakano H, Shindo M, Sakon S, Nishinaka S, Mihara M, Yagita H and Okumura K. . 1998 Proc. Natl. Acad. Sci. USA 95: 3537–3542.
Natoli G, Costanzo A, Moretti F, Fulco M, Balsano C and Levrero M. . 1997 J. Biol. Chem. 272: 26079–26082.
Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J and Dixit VM. . 1997a Science 276: 111–113.
Pan G, Ni J, Wei YF, Yu G, Gentz R and Dixit VM. . 1997b Science 277: 815–818.
Rainbow L, Platt GM, Simpson GR, Sarid R, Gao SJ, Stoiber H, Herrington CS, Moore PS and Schulz TF. . 1997 J. Virol. 71: 5915–5921.
Regnier CH, Song HY, Gao X, Goeddel DV, Cao Z and Rothe M. . 1997 Cell 90: 373–383.
Rothe M, Xiong J, Shu HB, Williamson K, Goddard A and Goeddel DV. . 1996 Proc. Natl. Acad. Sci. USA 93: 8241–8246.
Sarid R, Flore O, Bohenzky RA, Chang Y and Moore PS. . 1998 J. Virol. 72: 1005–1012.
Schulz TF. . 1998 J. Gen. Virol. 79: 1573–1591.
Shu HB, Halpin DR and Goeddel DV. . 1997 Immunity 6: 751–763.
Srinivasula SM, Ahmad M, Ottilie S, Bullrich F, Banks S, Wang Y, Fernandes-Alnemri T, Croce CM, Litwack G, Tomaselli KJ, Armstrong RC and Alnemri ES. . 1997 J. Biol. Chem. 272: 18542–18545.
Takeuchi M, Rothe M and Goeddel DV. . 1996 J. Biol. Chem. 271: 19935–19942.
Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer JL, Schroter M, Scaffidi C, Krammer PH, Peter ME and Tschopp J. . 1997 Nature 386: 517–521.
Van Antwerp DJ, Martin SJ, Kafri T, Green DR and Verma IM. . 1996 Science 274: 787–789.
Varfolomeev EE, Boldin MP, Goncharov TM and Wallach D. . 1996 J. Exp. Med. 183: 1271–1275.
Vincenz C and Dixit VM. . 1997 J. Biol. Chem. 272: 6578–6583.
Wang CY, Mayo MW and Baldwin Jr AS. . 1996 Science 274: 784–787.
Woronicz JD, Gao X, Cao Z, Rothe M and Goeddel DV. . 1997 Science 278: 866–869.
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 and Mak TW. . 1998 Science 279: 1954–1958.
Yeh WC, Shahinian A, Speiser D, Kraunus J, Billia F, Wakeham A, de la Pompa JL, Ferrick D, Hum B, Iscove N, Ohashi P, Rothe M, Goeddel DV and Mak TW. . 1997 Immunity 5: 715–725.
Zandi E, Rothwarf DM, Delhase M, Hayakawa M and Karin M. . 1997 Cell 91: 243–252.
Acknowledgements
We would like to thank Drs Tak Mak and Wen-Chen Yeh for FADD−/− cells, Drs Vishva Dixit, Emad Alnemri, Michael Wright, David Han, Hiroyasu Nakano, Richard Gaynor and Gioacchino Natoli for various expression plasmids, Dr Edward Clark for the NF-κB reporter plasmid, Dr Tim Rose for a DNA sample containing KSHV genome and Dr David Han for helpful discussions. PM Chaudhary was supported by a postdoctoral fellowship from the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation and the Stowers Institute for Medical Research.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chaudhary, P., Jasmin, A., Eby, M. et al. Modulation of the NF-κB pathway by virally encoded Death Effector Domains-containing proteins. Oncogene 18, 5738–5746 (1999). https://doi.org/10.1038/sj.onc.1202976
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1202976
Keywords
This article is cited by
-
CRISPR screens identify novel regulators of cFLIP dependency and ligand-independent, TRAIL-R1-mediated cell death
Cell Death & Differentiation (2023)
-
Nm23-H1 induces apoptosis in primary effusion lymphoma cells via inhibition of NF-κB signaling through interaction with oncogenic latent protein vFLIP K13 of Kaposi’s sarcoma-associated herpes virus
Cellular Oncology (2022)
-
Narciclasine, an isocarbostyril alkaloid, has preferential activity against primary effusion lymphoma
Scientific Reports (2020)
-
Epigenetic control in Kaposi sarcoma-associated herpesvirus infection and associated disease
Seminars in Immunopathology (2020)
-
Kaposi sarcoma
Nature Reviews Disease Primers (2019)