EB 病毒轉活化子Rta 會透過蛋白質激酶C-delta 促進細胞凋亡

Abstract

Transactivator, Rta, encoded by the Epstein-Barr virus (EBV) immediate -early gene, BRLF1, mediates the switch from latency into lytic cycle. In 1999, Swenson et al observed that Rta expression can induce cell apoptosis in normal human fibroblast (NHF) and human cervical carcinoma cell line (HeLa). This phenomenon also can be observed in our laboratory. According to these findings, we intended to investigate whether Rta contributes to cell apoptosis in the human epithelial cells, and whether apoptosis is important to EBV lytic cycle progression. At first, EBV Rta induced cell apoptosis could be demonstrated in HeLa and HEp2 cell lines. Secondly, Rta increased cleavage form of PKC-δ could be detected in the presence of Rta. Using rottlerin or PKC-δ dominant negative mutant to inhibit cellular PKC-δ activity, the phenomena that Rta induced cell apoptosis was reduced. Additionally, PKC-δ translocated from cytosol to nucleus was observed both in pRTS15 transiently transfected HeLa cells or trichostatin A (TSA) induced NA cells. Co-immunoprecipitation assay and immunofluorescent staining demonstrated the interaction between Rta and PKC-δ. Furthermore, the EBV lytic cycle progession was suppressed by using PKC-.δ inhibitor, rottlerin. However, EBV lytic cycle was not affected by treating cell with caspase inhibitor, Z-VAD-Fmk. Taken together, these studies suggest that PKC-δ is the upstream protein of Rta-mediated apoptotic signaling pathway and EBV lytic cycle progression induced by Rta.