Exp Mol Med.  2007 Feb;39(1):56-64.

STP-A11, an oncoprotein of Herpesvirus saimiri augments both NF-kappaB and AP-1 transcription activity through TRAF6

• Jeong S
• Cho IR
• An WG
• Jhun BH
• Lee BS
• Park K
• Chung YH

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.

Keyword

herpesvirus 2, saimirine; NF-kappaB; oncogene protein pp60 (v-src); Src; TNF receptor-associated factor 6; transcription factor AP-1

MeSH Terms

*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