| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
Departments of
*
Microbiology and
Internal Medicine, University of Iowa, and
Veterans Affairs Medical Center, Iowa City, IA 52242
TNFR-associated factor (TRAF)3, an adaptor protein that binds the cytoplasmic domains of both CD40 and the EBV-encoded oncoprotein latent membrane protein (LMP)1, is required for positive signaling by LMP1 but not CD40 in B lymphocytes. The present study further investigated how TRAF3 participates in LMP1 signaling. We found that TRAF3 mediates signaling both through direct interactions with the C-terminal activating region (CTAR)1 of LMP1 and through indirect interactions with the CTAR2 region of LMP1 in mouse B cells. Notably, our results demonstrated that the CTAR2 region appears to inhibit the recruitment of TRAF1 and TRAF2 to membrane rafts by the CTAR1 region. Additionally, the absence of TRAF2 in B cells resulted in only a modest reduction in CTAR1-mediated signals and no detectable effect on CTAR2-mediated signals. CTAR1 and CTAR2 cooperated to achieve the robust signaling activity of LMP1 when recruited to the same membrane microdomains in B cells. Interestingly, TRAF3 deficiency completely abrogated the cooperation between CTAR1 and CTAR2, supporting the hypothesis that TRAF3 participates in the physical interaction between CTAR1 and CTAR2 of LMP1. Together, our findings highlight the central importance of TRAF3 in LMP1-mediated signaling, which is critical for EBV persistent infection and EBV-associated pathogenesis.
This article has been cited by other articles:
|
|
 |
|
  Z. J. Kraus, H. Nakano, and G. A. Bishop TRAF5 is a critical mediator of in vitro signals and in vivo functions of LMP1, the viral oncogenic mimic of CD40 PNAS, October 6, 2009; 106(40): 17140 - 17145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Graham, C. R. Moore, and G. A. Bishop Roles of the TRAF2/3 Binding Site in Differential B Cell Signaling by CD40 and Its Viral Oncogenic Mimic, LMP1 J. Immunol., September 1, 2009; 183(5): 2966 - 2973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Peters, R. M. Plenge, R. R. Graham, D. M. Altshuler, K. L. Moser, P. M. Gaffney, and G. A. Bishop A novel polymorphism of the human CD40 receptor with enhanced function Blood, September 1, 2008; 112(5): 1863 - 1871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Ikeda, Y. Sekine, T. Yasui, K. Oritani, K. Sugiyma, R. Muromoto, N. Ohbayashi, A. Yoshimura, and T. Matsuda STAP-2 Negatively Regulates both Canonical and Noncanonical NF-{kappa}B Activation Induced by Epstein-Barr Virus-Derived Latent Membrane Protein 1 Mol. Cell. Biol., August 15, 2008; 28(16): 5027 - 5042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Mainou, D. N. Everly Jr., and N. Raab-Traub Unique Signaling Properties of CTAR1 in LMP1-Mediated Transformation J. Virol., September 15, 2007; 81(18): 9680 - 9692. [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]
|
|
|
|
|
|
P. Xie, B. S. Hostager, M. E. Munroe, C. R. Moore, and G. A. Bishop Cooperation between TNF Receptor-Associated Factors 1 and 2 in CD40 Signaling J. Immunol., May 1, 2006; 176(9): 5388 - 5400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wu, H. Nakano, and Z. Wu The C-terminal Activating Region 2 of the Epstein-Barr Virus-encoded Latent Membrane Protein 1 Activates NF-{kappa}B through TRAF6 and TAK1 J. Biol. Chem., January 27, 2006; 281(4): 2162 - 2169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wu, P. Xie, K. Welsh, C. Li, C.-Z. Ni, X. Zhu, J. C. Reed, A. C. Satterthwait, G. A. Bishop, and K. R. Ely LMP1 Protein from the Epstein-Barr Virus Is a Structural CD40 Decoy in B Lymphocytes for Binding to TRAF3 J. Biol. Chem., September 30, 2005; 280(39): 33620 - 33626. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
