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,
,§,¶
Graduate Programs in
*
Molecular Biology and
Immunology and Departments of
Microbiology and
§
Internal Medicine, University of Iowa, Iowa City, IA 52242; and
¶
Veterans Affairs Medical Center, Iowa City, IA 52242
Latent membrane protein 1 (LMP1) is required for EBV-induced
immortalization of human B cells, and expression of the protein in the
absence of other viral proteins leads to an activated phenotype in B
cells. It has been well documented that LMP1 causes B cells to
up-regulate adhesion molecules, such as LFA-1 and ICAM-1, and
coactivation molecules, such as B7-1 and CD23, as well as to activate
NF-
B. Ligation of the endogenous B cell CD40 molecule also induces
these and other activated phenotypic changes. Here, we report that
expression of LMP1 also activates B cells to secrete Ig and IL-6 and
rescues them from B cell receptor-mediated growth arrest analogous to
CD40 signaling. Furthermore, an HLA-A2LMP1 chimeric construct
demonstrates that the oligomerization of the carboxyl-terminal 200
amino acids of LMP1 is sufficient for B cell signaling. Finally, we
demonstrate that LMP1 and CD40 signaling pathways interact
cooperatively in inducing B cell effector
functions.
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C. R. Moore and G. A. Bishop Differential Regulation of CD40-Mediated TNF Receptor-Associated Factor Degradation in B Lymphocytes J. Immunol., September 15, 2005; 175(6): 3780 - 3789. [Abstract] [Full Text] [PDF]
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P. Xie and G. A. Bishop Roles of TNF Receptor-Associated Factor 3 in Signaling to B Lymphocytes by Carboxyl-Terminal Activating Regions 1 and 2 of the EBV-Encoded Oncoprotein Latent Membrane Protein 1 J. Immunol., November 1, 2004; 173(9): 5546 - 5555. [Abstract] [Full Text] [PDF]
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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]
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B. S. Hostager, S. A. Haxhinasto, S. L. Rowland, and G. A. Bishop Tumor Necrosis Factor Receptor-associated Factor 2 (TRAF2)-deficient B Lymphocytes Reveal Novel Roles for TRAF2 in CD40 Signaling J. Biol. Chem., November 14, 2003; 278(46): 45382 - 45390. [Abstract] [Full Text] [PDF]
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M. Baccam, S.-Y. Woo, C. Vinson, and G. A. Bishop CD40-Mediated Transcriptional Regulation of the IL-6 Gene in B Lymphocytes: Involvement of NF-{kappa}B, AP-1, and C/EBP J. Immunol., March 15, 2003; 170(6): 3099 - 3108. [Abstract] [Full Text] [PDF]
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K. D. Brown, B. S. Hostager, and G. A. Bishop Regulation of TRAF2 Signaling by Self-induced Degradation J. Biol. Chem., May 24, 2002; 277(22): 19433 - 19438. [Abstract] [Full Text] [PDF]
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L. K. Busch and G. A. Bishop Multiple Carboxyl-Terminal Regions of the EBV Oncoprotein, Latent Membrane Protein 1, Cooperatively Regulate Signaling to B Lymphocytes Via TNF Receptor-Associated Factor (TRAF)-Dependent and TRAF-Independent Mechanisms J. Immunol., November 15, 2001; 167(10): 5805 - 5813. [Abstract] [Full Text] [PDF]
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K. D. Brown, B. S. Hostager, and G. A. Bishop Differential Signaling and Tumor Necrosis Factor Receptor-associated Factor (TRAF) Degradation Mediated by CD40 and the Epstein-Barr Virus Oncoprotein Latent Membrane Protein 1 (LMP1) J. Exp. Med., April 16, 2001; 193(8): 943 - 954. [Abstract] [Full Text] [PDF]
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S. V. Jalukar, B. S. Hostager, and G. A. Bishop Characterization of the Roles of TNF Receptor-Associated Factor 6 in CD40-Mediated B Lymphocyte Effector Functions J. Immunol., January 15, 2000; 164(2): 623 - 630. [Abstract] [Full Text] [PDF]
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S. Aviel, G. Winberg, M. Massucci, and A. Ciechanover Degradation of the Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) by the Ubiquitin-Proteasome Pathway. TARGETING VIA UBIQUITINATION OF THE N-TERMINAL RESIDUE J. Biol. Chem., July 28, 2000; 275(31): 23491 - 23499. [Abstract] [Full Text] [PDF]
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B. S. Hostager, I. M. Catlett, and G. A. Bishop Recruitment of CD40 and Tumor Necrosis Factor Receptor-associated Factors 2 and 3 to Membrane Microdomains during CD40 Signaling J. Biol. Chem., May 12, 2000; 275(20): 15392 - 15398. [Abstract] [Full Text] [PDF]
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