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)

Kevin D Brown; Bruce S Hostager; Gail A Bishop

doi:10.1084/jem.193.8.943

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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)

Journal article

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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)

Kevin D Brown, Bruce S Hostager and Gail A Bishop

The Journal of experimental medicine, Vol.193(8), pp.943-954

04/16/2001

DOI: 10.1084/jem.193.8.943

PMCID: PMC2193407

PMID: 11304555

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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 κB 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.

B lymphocyte

CD40

signal transduction

Original

lymphoma

HHV4

Details

Title: Subtitle: 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)
Creators: Kevin D Brown - Immunology Graduate Program, University of Iowa
Bruce S Hostager - Department of Microbiology, University of Iowa
Gail A Bishop - Veteran's Affairs Medical Center, Iowa City, Iowa 52242
Resource Type: Journal article
Publication Details: The Journal of experimental medicine, Vol.193(8), pp.943-954
Publisher: The Rockefeller University Press
DOI: 10.1084/jem.193.8.943
PMID: 11304555
PMCID: PMC2193407
ISSN: 0022-1007
eISSN: 1540-9538
Language: English
Date published: 04/16/2001
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001117702771

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