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KMID : 0380220070400030341
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Journal of Biochemistry and Molecular Biology
2007 Volume.40 No. 3 p.341 ~ p.348
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STP-C, an Oncoprotein of Herpesvirus saimiri Augments the Activation of NF-&kgr;B through Ubiquitination of TRAF6
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Chung Young-Hwa
Jhun Byung-Hak
Ryu Su-Chak
Kim Heui-Soo
Kim Chul-Min
Kim Bong-Seok
Kim Young-Ok
Lee Sang-Jun
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Abstract
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Herpesvirus saimiri (HVS), a member of the &ggr;-herpesvirus family, encodes an oncoprotein called Saimiri Transforming Protein (STP) which is required for lymphoma induction in non-human primates. Previous study has shown that STP-C, an oncoprotein of HVS, activates NF-&kgr;B signaling pathway. However, the detailed mechanism of STP-Cmediated NF-&kgr;B activation has not been reported yet. We first report that STP-C interacts with TRAF6 protein in vivo and in vitro and further investigation shows that Glu12 residue of STP-C is critical for binding to TRAF6. Introduction of ubiquitin together with STP-C augments NF-&kgr;B activity compared to that of STP-C expression alone. STP-C expression further induces ubiquitination of endogenous TRAF6. In addition, either a deubiquitination enzyme, CYLD or a dominant negative E2-conjugation enzyme reduced NF-&kgr;B activity in spite of the presence of STP-C, supporting that the interaction between STP-C and TRAF6 induces ubiquitination of TRAF6. NF-&kgr;B activation by STP-C through the ubiquitinated TRAF6 causes the increased production of IL-8, an inflammatory chemokine and the enhanced expression of costimulatory molecule ICAM, which might ultimately contribute cellular transformation by the exposure of HVS-infected cells with inflammatory microenvironment and chronic activation.
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KEYWORD
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Herpesvirus saimiri, NF-&kgr, B, STP-C oncoprotein, TRAF6, Ubiquitin
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