Requirement for TRAF3 in signaling by LMP1 but not CD40 in B lymphocytes (2004)

Content Provider	CiteSeerX
Author	Xie, Ping Hostager, Bruce S. Bishop, Gail A.
Abstract	CD40, a member of the tumor necrosis factor receptor family, and the Epstein-Barr virus– encoded oncoprotein latent membrane protein 1 (LMP1) share several tumor necrosis factor receptor–associated factor (TRAF) adaptor proteins for signaling. Among these, TRAF3 was the first identified to directly bind both receptors, yet its role remains a mystery. To address this, we generated B cell lines deficient in TRAF3 by homologous recombination. We found that CD40 signals were normal in the absence of TRAF3, with the exception of moderately enhanced c-Jun NH2-terminal kinase (JNK) activation and antibody secretion. In sharp contrast, LMP1 signaling was markedly defective in TRAF3�/ � B cells. LMP1-induced activation of JNK and nuclear factor �B, up-regulation of CD23 and CD80, and antibody secretion were substantially affected by TRAF3 deficiency. Reconstitution of TRAF3 expression decreased CD40-induced JNK activation and antibody secretion, and fully restored LMP1 signaling. Although TRAF2 is widely believed to be important for LMP1 function, LMP1 signaling was intact in TRAF2�/ � B cells. Our data reveal that CD40 and LMP1 unexpectedly use TRAF3 in different ways, and that TRAF3 is required for LMP1-mediated activation of B cells. Key words: TNF-R family • Epstein-Barr virus • antibody secretion • signal transduction • B cell
File Format	PDF
Journal	J Exp Med
Language	English
Publisher Date	2004-01-01
Access Restriction	Open
Subject Keyword	Antibody Secretion Lmp1 Signaling Adaptor Protein Nuclear Factor Epstein-barr Virus Lmp1 Function Traf3 Cell Different Way Data Reveal Oncoprotein Latent Membrane Protein Tumor Necrosis Factor Receptor Family Homologous Recombination Sharp Contrast Lmp1-induced Activation Traf3 Expression Cd40 Signal Traf2 Cell Traf3 Deficiency Lmp1-mediated Activation Key Word Cd40-induced Jnk Activation Cell Line Deficient Enhanced C-jun Nh2-terminal Kinase
Content Type	Text
Resource Type	Article