Published online Nov 12, 2014. doi: 10.5501/wjv.v3.i4.22
Revised: July 14, 2014
Accepted: September 18, 2014
Published online: November 12, 2014
AIM: To investigate the role of nuclear factor κB (NF-κB) in the regulation of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) in EBV transformed cells.
METHODS: LMP1 expression was examined in EBV transformed human B lymphocytes with modulation of NF-κB activity.
RESULTS: EBV infection is associated with several human cancers. EBV LMP1 is required for efficient transformation of adult primary B cells in vitro, and is expressed in several pathogenic stages of EBV-associated cancers. Regulation of EBV LMP1 involves both viral and cellular factors. LMP1 activates NF-κB signaling pathway that is a part of the EBV transformation program. However, the relation between NF-κB and LMP1 expression is not well established yet. In this report, we found that blocking the NF-κB activity by Inhibitor of κB stimulated LMP1 expression, while the overexpression of NF-κB repressed LMP1 expression in EBV-transformed IB4 cells. In addition, LMP1 repressed its own promoter activities in reporter assays, and the repression was associated with the activation of NF-κB. Moreover, NF-κB alone is sufficient to repress LMP1 promoter activities.
CONCLUSION: Our data suggest LMP1 may repress its own expression through NF-κB in EBV transformed cells and shed a light on LMP1 regulation during EBV transformation.
Core tip: We find a classical feedback inhibition of Epstein Barr virus (EBV) Latent membrane protein 1 (LMP1) and nuclear factor κB (NF-κB): LMP1 activates NF-κB, and NF-κB inhibits LMP1 expression. The regulatory loop may benefit EBV transformation processes.