ASK1 is Involved in EBV LMP1-induced NF-kappaB Activation.
- Author:
Yoon Jae SONG
1
Author Information
- Publication Type:Original Article
- Keywords: Epstein-Barr virus; Latent membrane protein 1; ASK1; NF-kappaB
- MeSH: Animals; B-Lymphocytes; Burkitt Lymphoma; Cell Line; Fibroblasts; Herpesvirus 4, Human; Lymphocyte Activation; MAP Kinase Kinase Kinase 5; Membrane Proteins; Mice; NF-kappa B; Reactive Oxygen Species
- From:Journal of Bacteriology and Virology 2012;42(1):63-68
- CountryRepublic of Korea
- Language:English
- Abstract: Epstein-Barr virus (EBV) latent infection transforms B lymphocytes into proliferating lymphoblastoid cell lines (LCLs). EBV latent infection membrane protein 1 (LMP1) is required for EBV-mediated B lymphocyte transformation, and LMP1-induced NF-kappaB activation is essential for LCL survival. Previously, it was reported that the level of reactive oxygen species (ROS) and the expression of apoptosis signal-regulating kinase 1 (ASK1) are elevated in EBV-positive Burkitt's lymphoma (BL) cells, the potential role of ASK1 in LMP1-induced NF-kappaB activation was thus investigated in this study. In EBV-positive BL cells, ASK1 was highly expressed and activated. In addition, TRAF6-ASK1 interaction was significantly increased in EBV-positive BL cells. Interestingly, the expression of LMP1 alone facilitated ASK1 activation. The expression of a dominant negative ASK1 mutant (ASK1KM) strongly blocked LMP1-induced NF-kappaB activation. Furthermore, LMP1-induced NF-kappaB activation was significantly reduced in ASK1 knock out (ASK1-/-) mouse embryonic fibroblasts (MEFs). Taken together, these results demonstrate that ASK1 is activated by LMP1 and is critical for LMP1-induced NF-kappaB activation.
