Localization of the major NF-kappaB-activating site and the sole TRAF3 binding site of LMP-1 defines two distinct signaling motifs.
J Biol Chem
; 272(32): 19777-84, 1997 Aug 08.
Article
em En
| MEDLINE
| ID: mdl-9242637
ABSTRACT
The TRAF3 molecule interacts with the cytoplasmic carboxyl terminus (COOH terminus) of the Epstein-Barr virus-encoded oncogene LMP-1. NF-kappaB 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-kappaB-activating potential. Deletion mapping localized the major NF-kappaB 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-kappaB activation occur through two separate motifs at opposite ends of the LMP-1 COOH-terminal sequence.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Proteínas Oncogênicas Virais
/
Proteínas da Matriz Viral
/
NF-kappa B
/
Dedos de Zinco
/
Herpesvirus Humano 4
/
Antígenos Virais
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos