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생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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STP-C, an Oncoprotein of Herpesvirus saimiri Augments the Activation of NF-κB through Ubiquitination of TRAF6

  • Chung, Young-Hwa (Department of Nanomaterials Engineering, Pusan National University) ;
  • Jhun, Byung-Hak (Department of Nanomaterials Engineering, Pusan National University) ;
  • Ryu, Su-Chak (Department of Nanomaterials Engineering BK21 Nano Fusion Technology Team, Joint Research Center of PNU-Fraunhofer IGB, Pusan National University) ;
  • Kim, Heui-Soo (Department of Biology, Pusan National University) ;
  • Kim, Cheol-Min (Department of Biochemistry, Pusan National University) ;
  • Kim, Bong-Seok (Biotechnology Research Center, National Fisheries Research & Development Institute) ;
  • Kim, Young-Ok (Biotechnology Research Center, National Fisheries Research & Development Institute) ;
  • Lee, Sang-Jun (Biotechnology Research Center, National Fisheries Research & Development Institute)
  • 발행 : 2007.05.31
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초록

Herpesvirus saimiri (HVS), a member of the $\delta$-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-$\kappa$B signaling pathway. However, the detailed mechanism of STP-Cmediated NF-$\kappa$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 $Glu_{12}$ residue of STP-C is critical for binding to TRAF6. Introduction of ubiquitin together with STP-C augments NF-$\kappa$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-$\kappa$B activity in spite of the presence of STP-C, supporting that the interaction between STP-C and TRAF6 induces ubiquitination of TRAF6. NF-$\kappa$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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