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STP-A11, an oncoprotein of Herpesvirus saimiri augments both NF-kappaB and AP-1 transcription activity through TRAF6
Experimental & Molecular Medicine ; : 56-64, 2007.
Artículo en Inglés | WPRIM | ID: wpr-37555
ABSTRACT
Herpesvirus saimiri (HVS), a member of the gamma-herpesvirus family, encodes an oncoprotein called Saimiri Transforming Protein (STP) which is required for lymphoma induction in non-human primates. However, a detailed mechanism of STP-A11-induced oncogenesis has not been revealed yet. We first report that STP-A11 oncoprotein interacts with TNF-alpha receptor-associated factor (TRAF) 6 in vivo and in vitro. Mutagenesis analysis of the TRAF6-binding motif 10PQENDE15 in STP-A11 reveals that Glu (E)12 residue is critical for binding to TRAF6 and NF-kappaB activation. Interestingly, co-expression of E12A mutant, lack of TRAF6 binding, with cellular Src (Src) results in decreased transcriptional activity of Stat3 and AP-1, a novel target of STP-A11 compared to that of wild type. Furthermore, the presence of STP-A11 enhances the association of TRAF6 with Src and induces the translocation of both TRAF6 and Src to a nonionic detergent-insoluble fraction. Taken together, these studies suggest that STP-A11 oncoprotein up-regulates both NF-kappaB and AP-1 transcription activity through TRAF6, which would ultimately contribute cellular transformation.
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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Unión Proteica / Solubilidad / Transcripción Genética / Línea Celular / Proteínas Oncogénicas Virales / FN-kappa B / Proteínas Proto-Oncogénicas pp60(c-src) / Herpesvirus Saimiriino 2 / Factor de Transcripción AP-1 / Factor 6 Asociado a Receptor de TNF Límite: Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2007 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Unión Proteica / Solubilidad / Transcripción Genética / Línea Celular / Proteínas Oncogénicas Virales / FN-kappa B / Proteínas Proto-Oncogénicas pp60(c-src) / Herpesvirus Saimiriino 2 / Factor de Transcripción AP-1 / Factor 6 Asociado a Receptor de TNF Límite: Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2007 Tipo del documento: Artículo