| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
GSF-National Research Center for Environment and Health, Department of Gene Vectors, D-81377 Munich, Germany [U. D., B. N., E. K., G. R., W. H.], and McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706 [M. L. S.]
The EBV latent membrane protein 1 (LMP1) is an integral membrane protein that acts like a constitutively activated receptor. LMP1 interacts with members of the tumor necrosis factor receptor-associated factor family, as well as with tumor necrosis factor receptor-associated death domain, resulting in induction of nuclear factor-
B, the p38 mitogen-activated protein kinase pathway, and the c-Jun NH2-terminal kinase activator protein 1-signaling cascade. The binding of Janus kinase 3 results in activation of signal transducers and activators of transcription. The domain structure of LMP1 has been mapped extensively, but the quantitative contribution of distinct LMP1 domains to the efficiency of B-cell proliferation by EBV has not been determined. On the basis of the maxi-EBV system, which allows us to introduce and study mutations in the context of the complete EBV genome, a panel of 10 EBV mutants with alterations in the LMP1 gene locus was established. The mutant EBVs were tested for their efficiency to induce and maintain proliferation of clonal B-cell lines in vitro. Surprisingly and with reduced frequency, EBV mutants which deleted LMP1’s COOH terminus, transmembrane domains, or the entire open reading frame were able to generate proliferating B-cell clones that were dependent on the presence of human fibroblast feeder cells. A B-cell clone carrying the LMP1-null mutant EBV genome was also analyzed for oncogenicity in severe combined immunodeficiency mice. Our results demonstrate that LMP1 is critical but not mandatory for the generation of proliferating B cells in vitro. LMP1 functions greatly contribute to EBV’s transformation potential and appear essential for its oncogenicity in severe combined immunodeficiency mice.
This article has been cited by other articles:
|
|
 |
|
  Y.-R. Chen, M.-T. Liu, Y.-T. Chang, C.-C. Wu, C.-Y. Hu, and J.-Y. Chen Epstein-Barr Virus Latent Membrane Protein 1 Represses DNA Repair through the PI3K/Akt/FOXO3a Pathway in Human Epithelial Cells J. Virol., August 15, 2008; 82(16): 8124 - 8137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Y. Lee and B. Sugden The LMP1 oncogene of EBV activates PERK and the unfolded protein response to drive its own synthesis Blood, February 15, 2008; 111(4): 2280 - 2289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Lambert and O. M. Martinez Latent Membrane Protein 1 of EBV Activates Phosphatidylinositol 3-Kinase to Induce Production of IL-10 J. Immunol., December 15, 2007; 179(12): 8225 - 8234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-F. Chiu, C.-P. Tung, Y.-H. Lee, W.-H. Wang, C. Li, J.-Y. Hung, C.-Y. Wang, Y. Kawaguchi, and S.-T. Liu A comprehensive library of mutations of Epstein Barr virus J. Gen. Virol., September 1, 2007; 88(9): 2463 - 2472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lee and B. Sugden A Membrane Leucine Heptad Contributes to Trafficking, Signaling, and Transformation by Latent Membrane Protein 1 J. Virol., September 1, 2007; 81(17): 9121 - 9130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Soni, T. Yasui, E. Cahir-McFarland, and E. Kieff LMP1 Transmembrane Domain 1 and 2 (TM1-2) FWLY Mediates Intermolecular Interactions with TM3-6 To Activate NF-{kappa}B J. Virol., November 1, 2006; 80(21): 10787 - 10793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Altmann, D. Pich, R. Ruiss, J. Wang, B. Sugden, and W. Hammerschmidt Transcriptional activation by EBV nuclear antigen 1 is essential for the expression of EBV's transforming genes PNAS, September 19, 2006; 103(38): 14188 - 14193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Brinkmann and T. F. Schulz Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae. J. Gen. Virol., May 1, 2006; 87(Pt 5): 1047 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Suarez, O. Lortholary, O. Hermine, and M. Lecuit Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation Blood, April 15, 2006; 107(8): 3034 - 3044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Hong, M. L. Gulley, W.-H. Feng, H.-J. Delecluse, E. Holley-Guthrie, and S. C. Kenney Epstein-Barr Virus Lytic Infection Contributes to Lymphoproliferative Disease in a SCID Mouse Model J. Virol., November 15, 2005; 79(22): 13993 - 14003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. T. Lu, R. L. Dryer, C. Song, and L. R. Covey Maintenance of the CD40-related immunodeficient response in hyper-IgM B cells immortalized with a LMP1-regulated mini-EBV J. Leukoc. Biol., September 1, 2005; 78(3): 620 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Kelly, A. E. Milner, R. J. Tierney, D. S. G. Croom-Carter, M. Altmann, W. Hammerschmidt, A. I. Bell, and A. B. Rickinson Epstein-Barr Virus Nuclear Antigen 2 (EBNA2) Gene Deletion Is Consistently Linked with EBNA3A, -3B, and -3C Expression in Burkitt's Lymphoma Cells and with Increased Resistance to Apoptosis J. Virol., August 15, 2005; 79(16): 10709 - 10717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Peng, S. C. Moses, J. Tan, E. Kremmer, and P. D. Ling The Epstein-Barr Virus EBNA-LP Protein Preferentially Coactivates EBNA2-Mediated Stimulation of Latent Membrane Proteins Expressed from the Viral Divergent Promoter J. Virol., April 1, 2005; 79(7): 4492 - 4505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. N. Everly Jr., B. A. Mainou, and N. Raab-Traub Induction of Id1 and Id3 by Latent Membrane Protein 1 of Epstein-Barr Virus and Regulation of p27/Kip and Cyclin-Dependent Kinase 2 in Rodent Fibroblast Transformation J. Virol., December 15, 2004; 78(24): 13470 - 13478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Gordadze, C. W. Onunwor, R. Peng, D. Poston, E. Kremmer, and P. D. Ling EBNA2 Amino Acids 3 to 30 Are Required for Induction of LMP-1 and Immortalization Maintenance J. Virol., April 15, 2004; 78(8): 3919 - 3929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Lam, M. L. Sandberg, and B. Sugden High Physiological Levels of LMP1 Result in Phosphorylation of eIF2{alpha} in Epstein-Barr Virus-Infected Cells J. Virol., February 15, 2004; 78(4): 1657 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. D'Souza, L. C. Edelstein, P. M. Pegman, S. M. Smith, S. T. Loughran, A. Clarke, A. Mehl, M. Rowe, C. Gelinas, and D. Walls Nuclear Factor {kappa}B-Dependent Activation of the Antiapoptotic bfl-1 Gene by the Epstein-Barr Virus Latent Membrane Protein 1 and Activated CD40 Receptor J. Virol., February 15, 2004; 78(4): 1800 - 1816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Humme, G. Reisbach, R. Feederle, H.-J. Delecluse, K. Bousset, W. Hammerschmidt, and A. Schepers The EBV nuclear antigen 1 (EBNA1) enhances B cell immortalization several thousandfold PNAS, September 16, 2003; 100(19): 10989 - 10994. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
