| Summary: | 碩士 === 長庚大學 === 基礎醫學研究所 === 90 === Epstein-Barr virus is a human herpesvirus that infects human lymphocytes and epithelial cells. It is associated with several human malignant diseases such as Burkitt''s lymphoma and nasopharyngeal carcinoma (NPC). The EBV genome exists in a latent stage in these malignant cells and only a limited number of EBV gene products are expressed. Among the latent gene products, LMP1 is the most important one reported to be involved in the transformation of rodent fibroblast cells, human epithelial and B cells. LMP1 can activate transcription factor NF-kB through a pathway that involves NF-kB-inducing kinase and IkB kinases IKKa and IKKb. In this study, I have examined the possibility that LMP1 may also activate NF-kB through another signaling pathway including 21 kDa GTPase Cdc42 and p21Cdc42/Rac1-activated kinases (PAKs). Results showed that expression of LMP1 in human 293 cells activated endogenous Cdc42. Expression of wild type Cdc42 in Balb/3T3 and human epithelial C-33A cells enhanced the LMP1-mediated NF-kB activation by more than 2.5 fold, and expression of dominant negative Cdc42 in C-33A inhibited NF-kB activation mediated by LMP1. However, the activity of PAK2 remains the same regardless the pressence or absense of LMP1. Moreover, expression of wild type, inactive form or active form PAK2 had little effect on the LMP1-mediated NF-kB activation in Balb/3T3 and C-33A Cells.
These results taken together suggest that Cdc42, but not PAK2,is involved in the NF-kB signaling pathway elicited by LMP1 in cells.
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