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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).
- Source :
-
The Journal of experimental medicine [J Exp Med] 2001 Apr 16; Vol. 193 (8), pp. 943-54. - Publication Year :
- 2001
-
Abstract
- Latent membrane protein 1 (LMP1) plays a critical role in B cell transformation by Epstein-Barr virus (EBV) and appears to mimic a constitutively active CD40 receptor. Intracellular tumor necrosis factor (TNF) receptor-associated factor (TRAF) adapter proteins, shown to contribute to signaling by both CD40 and LMP1, were recruited by both molecules to lipid-enriched membrane rafts. However, we found that TRAFs 2 and 3 were subsequently degraded after CD40- but not LMP1-induced signaling. This degradation was proteasome-dependent and required direct TRAF binding by CD40. Using a model system designed to directly compare the signaling potency of the cytoplasmic domains of LMP1 and CD40 in B lymphocytes, we found that LMP1 more potently activates c-Jun kinase and nuclear factor kappaB and induces higher levels of several B cell effector functions than does CD40. This suggests that LMP1 utilizes a modified CD40 signaling pathway. Failure to regulate TRAFs may contribute to the enhanced capacity of LMP1 to activate B cells as well as promote B cell transformation.
- Subjects :
- Animals
B-Lymphocytes virology
CD40 Antigens genetics
Cell Line
Cell Membrane immunology
Herpesvirus 4, Human physiology
Humans
Lymphocyte Activation
Mice
Recombinant Proteins metabolism
Signal Transduction
TNF Receptor-Associated Factor 2
TNF Receptor-Associated Factor 3
Transfection
B-Lymphocytes immunology
CD40 Antigens physiology
Proteins metabolism
Receptors, Tumor Necrosis Factor physiology
Viral Matrix Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1007
- Volume :
- 193
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 11304555
- Full Text :
- https://doi.org/10.1084/jem.193.8.943