Cho Il-Rae, Jeong Sunam, Jhun Byung Hak, An Won G, Lee BokSoo, Kwak Youn-Tae, Lee Sun-Hwa, Jung Jae U, Chung Young-Hwa
Department of Nanomedical Engineering, Joint-Research Center of Pusan National University-Fraunhofer IGB, Pusan National University, Miryang, Gyeongnam 627-706, Korea.
Virology. 2007 Mar 1;359(1):37-45. doi: 10.1016/j.virol.2006.09.001. Epub 2006 Oct 9.
Although Saimiri Transforming Protein (STP)-A11, an oncoprotein of Herpesvirus saimiri, has been known to activate NF-kappaB signaling pathway, the detailed mechanism has not been reported yet. We herein report that STP-A11 activates non-canonical NF-kappaB pathway, resulting in p100 processing to p52. In addition, translocation of p52 protein (NF-kappaB2) into the nucleus is observed by the expression of STP-A11. STP-A11-mediated processing of p100 to p52 protein requires proteosome-mediated proteolysis because MG132 treatment clearly blocked p52 production in spite of the expression of STP-A11. Analysis of STP-A11 mutants to activate NF-kappaB2 pathway discloses the requirement of TRAF6-binding site not Src-binding site for STP-A11-mediated NF-kappaB2 pathway. Blockage of STP-A11-mediated p52 production using siRNA against p52 enhanced a chemotherapeutic drug-mediated cell death, suggesting that p52 production induced by the expression of STP-A11 would contribute to cellular transformation, which results from a resistance to cell death.
虽然已知松鼠猴疱疹病毒的癌蛋白——松鼠猴转化蛋白（STP）-A11可激活核因子κB信号通路，但其详细机制尚未见报道。我们在此报告，STP-A11激活非经典核因子κB通路，导致p100加工成p52。此外，通过STP-A11的表达可观察到p52蛋白（核因子κB2）易位至细胞核。STP-A11介导的p100加工成p52蛋白需要蛋白酶体介导的蛋白水解，因为尽管有STP-A11的表达，MG132处理仍明显阻断了p52的产生。对激活核因子κB2通路的STP-A11突变体的分析揭示，STP-A11介导的核因子κB2通路需要TRAF6结合位点而非Src结合位点。使用针对p52的小干扰RNA阻断STP-A11介导的p52产生可增强化疗药物介导的细胞死亡，这表明STP-A11表达诱导的p52产生有助于细胞转化，而细胞转化是由对细胞死亡的抗性导致的。
