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Localization of the Major NF-κB-activating Site and the Sole TRAF3 Binding Site of LMP-1 Defines Two Distinct Signaling Motifs

Brodeur, Scott R. and Cheng, Genhong and Baltimore, David and Thorley-Lawson, David A. (1997) Localization of the Major NF-κB-activating Site and the Sole TRAF3 Binding Site of LMP-1 Defines Two Distinct Signaling Motifs. Journal of Biological Chemistry, 272 (32). pp. 19777-19784. ISSN 0021-9258.

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The TRAF3 molecule interacts with the cytoplasmic carboxyl terminus (COOH terminus) of the Epstein-Barr virus-encoded oncogene LMP-1. NF-κB activation is a downstream signaling event of tumor necrosis factor receptor-associated factor (TRAF) molecules in other signaling systems (CD40 for example) and is an event caused by LMP-1 expression. One region capable of TRAF3 interaction in LMP-1 is the membrane-proximal 45 amino acids (188–242) of the COOH terminus. We show that this region contains the only site for binding of TRAF3 in the 200-amino acid COOH terminus of LMP-1. The site also binds TRAF2 and TRAF5, but not TRAF6. TRAF3 binds to critical residues localized between amino acids 196 and 212 (HHDDSLPHPQQATDDSG), including the PXQX(T/S) motif, that share limited identity to the CD40 receptor TRAF binding site (TAAPVQETL). Mutation of critical residues in the TRAF3 binding site of LMP-1 that prevents binding of TRAF2, TRAF3, and TRAF5 does not affect NF-κB-activating potential. Deletion mapping localized the major NF-κB activating region of LMP-1 to critical residues in the distal 4 amino acids of the COOH terminus (383–386). Therefore, TRAF3 binding and NF-κB activation occur through two separate motifs at opposite ends of the LMP-1 COOH-terminal sequence.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 1997 by The American Society for Biochemistry and Molecular Biology, Inc. This work was supported by U.S. Public Health Service Grants CA 31893 and CA 65883. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Funding AgencyGrant Number
U.S. Public Health Service (USPHS)CA 31893
U.S. Public Health Service (USPHS)CA 65883
Record Number:CaltechAUTHORS:20120119-140427290
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:28868
Deposited By: Tony Diaz
Deposited On:13 Apr 2012 21:24
Last Modified:06 Nov 2017 23:17

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