STP-A11, an oncoprotein of Herpesvirus saimiri augments both NF-kappaB and AP-1 transcription activity through TRAF6.
- Author:
Sunam JEONG
1
;
Il Rae CHO
;
Won Gun AN
;
Byung Hak JHUN
;
Bok Soo LEE
;
Keerang PARK
;
Young Hwa CHUNG
Author Information
1. Department of Nanomedical Engineering, Joint Research Center of Pusan National University-Fraunhofer IGB, BK21 Nano Fusion Technology Team, Pusan National University, Miryang 627-706, Korea. younghc@pusan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
herpesvirus 2, saimirine;
NF-kappaB;
oncogene protein pp60 (v-src);
Src;
TNF receptor-associated factor 6;
transcription factor AP-1
- MeSH:
*Transcription, Genetic;
Transcription Factor AP-1/agonists/*metabolism;
TNF Receptor-Associated Factor 6/*metabolism;
Solubility;
STAT3 Transcription Factor/metabolism;
Proto-Oncogene Proteins pp60(c-src)/metabolism;
Protein Binding;
Oncogene Proteins, Viral/*metabolism;
NF-kappa B/agonists/*metabolism;
Ions;
Humans;
Herpesvirus 2, Saimiriine/*metabolism;
Detergents;
Cell Line
- From:Experimental & Molecular Medicine
2007;39(1):56-64
- CountryRepublic of Korea
- Language:English
-
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.
