Abstract
The LMP-1 oncoprotein of EBV is required to maintain proliferation of infected B-cells and shares several features with CD40, TNF-R1, and related receptors. Members of this family can bind TRAF and TRADD molecules and activate NF-κB and AP-1, as can LMP-1. While CD40 and TNF-R1 are dependent on binding their ligands for their signaling, LMP-1 apparently is not. We have found that LMP-1 can act as a governor of cell proliferation and thereby limit its own activities. Its inhibition of proliferation is not mediated by apoptosis but results in cytostasis in four cell lines tested. The structural moiety of LMP-1 that distinguishes it from CD40 and TNF-R1, its amino-terminus and multiple membrane spanning segments, alone can mediate its cytostatic activity.
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References
Alderson MR, Tough TW, Braddy S, Davis ST, Roux E, Schooley K, Miller RE and Lynch DH . 1994 Int Immunol 6: 1799–1806
Arden JR, Segredo V, Wang Z, Lameh J and Sadee W . 1995 J Neurochem 65: 1636–1645
Berberich I, Shu GL and Clark EA . 1994 J Immunol 153: 4357–4366
Bertin J, Mendrysa SM, LaCount DJ, Gaur S, Krebs JF, Armstrong RC, Tomaselli KJ and Friesen PD . 1996 J Virol 70: 6251–6259
Bloss T, Kaykas A and Sugden B . 1999 J Gen Virol 80: 3227–3232
Brodeur SR, Cheng G, Baltimore D and Thorley-Lawson D . 1997 J Biol Chem 272: 19777–19784
Camplejohn RS . 1994 J Microsc 176: 1–7
Cuomo L, Ramquist T, Trivedi P, Wang F, Klein G and Masucci MG . 1992 Int J Cancer 51: 949–955
Debbas M and White E . 1993 Genes Dev 7: 546–554
Deuschle U, Meyer WK and Thiesen HJ . 1995 Mol Cell Biol 15: 1907–1914
Devergne O, Hatzivassiliou E, Izumi KM, Kaye KM, Kleijnen MF, Kieff E and Mosialos G . 1996 Mol Cell Biol 16: 7098–7108
Evan G and Littlewood T . 1998 Science 281: 1317–1322
Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, Waters CM, Penn LZ and Hancock DC . 1992 Cell 69: 119–128
Faure S, Vigneron S, Doree M and Morin N . 1997 EMBO J 16: 5550–5561
Floettmann JE, Ward K, Rickinson AB and Rowe M . 1996 Virology 223: 29–40
Gires O, Zimber SU, Gonnella R, Ueffing M, Marschall G, Zeidler R, Pich D and Hammerschmidt W . 1997 EMBO J 16: 6131–6140
Graham FL, Smiley J, Russell WC and Nairn R . 1977 J Gen Virol 36: 59–74
Hammerschmidt W, Sugden B and Baichwal VR . 1989 J Virol 63: 2469–2475
Harvey DM and Levine AJ . 1991 Genes Dev 5: 2375–2385
Hockenbery D, Nunez G, Milliman C, Schreiber RD and Korsmeyer SJ . 1990 Nature 348: 334–336
Howes KA, Ransom N, Papermaster DS, Lasudry JG, Albert DM and Windle JJ . 1994 Genes Dev 8: 1300–1310
Hsu H, Xiong J and Goeddel DV . 1995 Cell 81: 495–504
Hu HM, O'Rourke K, Boguski MS and Dixit VM . 1994 J Biol Chem 269: 30069–30072
Izumi KM and Kieff ED . 1997 Proc Natl Acad Sci USA 94: 12592–12597
Jacob MC, Favre M and Bensa JC . 1991 Cytometry 12: 550–558
Kavathas P, Bach FH and DeMars R . 1980 Proc Natl Acad Sci USA 77: 4251–4255
Kieser A, Kilger E, Gires O, Ueffing M, Kolch W and Hammerschmidt W . 1997 EMBO J 16: 6478–6485
Knutson JC and Yee D . 1987 Anal Biochem 164: 44–52
Martin J and Sugden B . 1991a Cell Growth Differ 2: 653–600
Martin J and Sugden B . 1991b J Virol 65: 3246–3258
Mitchell T and Sugden B . 1995 J Virol 69: 2968–2976
Mosialos G, Birkenbach M, Yalamanchili R, VanArsdale T, Ware C and Kieff E . 1995 Cell 80: 389–399
O'Reilly LA, Huang DC and Strasser A . 1996 EMBO J 15: 6979–6990
Petti L and DiMaio D . 1994 J Virol 68: 3582–3592
Petti LM, Reddy V, Smith SO and DiMaio D . 1997 J Virol 71: 7318–7327
Potten CS, Wilson JW and Booth C . 1997 Stem Cells 15: 82–93
Puls A, Eliopoulos AG, Nobes CD, Bridges T, Young LS and Hall A . 1999 J Cell Sci 112: 2983–2992
Rooney RD, Tuazon PT, Meek WE, Carroll EJ, Hagen JJ, Gump EL, Monnig CA, Lugo T and Traugh JA . 1996 J Biol Chem 271: 21498–21504
Rothe M, Wong SC, Henzel WJ and Goeddel DV . 1994 Cell 78: 681–692
Rowe M, Rowe DT, Gregory CD, Young LS, Farrell PJ, Rupani H and Rickinson AB . 1987 EMBO J 6: 2743–2751
Sandberg M, Hammerschmidt W and Sugden B . 1997 J Virol 71: 4649–4656
Schleiss MR, Degnin CR and Geballe AP . 1991 J Virol 65: 6782–6789
Serrano M, Lin AW, McCurrach ME, Beach D and Owe SW . 1997 Cell 88: 593–602
Shi Y, Glynn JM, Guilbert LJ, Cotter TG, Bissonnette RP and Green DR . 1992 Science 257: 212–214
Sugden B, Marsh K and Yates J . 1985 Mol Cell Biol 5: 410–413
Sugden B, Phelps M and Domoradzki J . 1979 J Virol 31: 590–595
Tewari M, Telford WG, Miller RA and Dixit VM . 1995 J Biol Chem 270: 22705–22708
Weigel R and Miller G . 1983 Virology 125: 287–298
Wilson PT and Bourne HR . 1995 J Biol Chem 270: 9667–9675
Acknowledgements
We thank Ashok Aiyar, Paul Lambert, David Mackey and Mary Ellen Perry for their critical review of this manuscript. We also thank Elizabeth R Leight for performing some of the long-term assays for inhibition of cell proliferation and Tim Bloss and Wolfgang Hammerschmidt for constructing some of the vectors we studied. This work was supported by Public Health Service grants CA-22443, CA-07175, T32-CA-09135, and CA-70723.
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Kaykas, A., Sugden, B. The amino-terminus and membrane-spanning domains of LMP-1 inhibit cell proliferation. Oncogene 19, 1400–1410 (2000). https://doi.org/10.1038/sj.onc.1203365
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DOI: https://doi.org/10.1038/sj.onc.1203365
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