STP-A11, an oncoprotein of Herpesvirus saimiri augments both NF-kappaB and AP-1 transcription activity through TRAF6.
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 (10)PQENDE(15) 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.
Jeong
Sunam
S
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.
Cho
Il-Rae
IR
An
Won Gun
WG
Jhun
Byung Hak
BH
Lee
BokSoo
B
Park
Keerang
K
Chung
Young-Hwa
YH
D002460:Cell Line; D003902:Detergents; D006567:Herpesvirus 2, Saimiriine / Q000378:metabolism*; D006801:Humans; D007477:Ions; D016328:NF-kappa B / Q000819:agonists / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D011485:Protein Binding; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012995:Solubility; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000819:agonists / Q000378:metabolism*; D014158:Transcription, Genetic
D003902:Detergents; D007477:Ions; D016328:NF-kappa B; D009856:Oncogene Proteins, Viral; D050796:STAT3 Transcription Factor; D048029:TNF Receptor-Associated Factor 6; D018808:Transcription Factor AP-1; D016392:Proto-Oncogene Proteins pp60(c-src)