J Bacteriol Virol.  2012 Mar;42(1):63-68. 10.4167/jbv.2012.42.1.63.

ASK1 is Involved in EBV LMP1-induced NF-kappaB Activation

• Song YJ

• KMID: 1434774
• DOI: http://doi.org/10.4167/jbv.2012.42.1.63

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.

Keyword

Epstein-Barr virus; Latent membrane protein 1; ASK1; NF-kappaB

MeSH Terms

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
MAP Kinase Kinase Kinase 5
Membrane Proteins
NF-kappa B
Reactive Oxygen Species