Epstein-Barr virus encoded latent membrane protein 1 induces TRAF1 expression to promote anti-apoptosis activity via NF-kappaB signaling pathway in nasopharyngeal carcinoma.
OBJECTIVE
To identify whether Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) can induce tumor necrosis factor receptor-associated factor 1 (TRAF1) expression and promote its anti-apoptosis activity via the NF-kappaB signaling pathway, and assess that LMP1 suppresses apoptosis in nasopharyngeal carcinoma (NPC).


METHODS
A stable transfected cell line HNE2-LMP1 was established by introducing LMP1 cDNA into HNE2 cells. Transactivation of TRAF1 was determined by luciferase reporter assay, while expression of TRAF1 mRNA was detected by RT-PCR and expression of TRAF1 protein and caspase 3 by Western blot analysis. Apoptosis activity was observed through fluorescence staining.


RESULTS
LMP1 induced TRAF1 expression in NPC cells and caused a decrease in apoptosis. This induction could be blocked by antisense LMP1. Moreover, LMP1-mediated induction of a TRAF1 promoter-driven reporter gene was significantly impaired when the kappaB site kappaB1 or kappaB5 was disrupted, whereas mutation of kappaB3 had only a minor effect on LMP1 dependent up-regulation of the reporter gene.


CONCLUSIONS
LMP1 induces TRAF1 expression and promotes its anti-apoptosis activity via the NF-kappaB signaling pathway, which may be one of the mechanisms that LMP1 uses to suppress apoptosis in NPC cells.
Wang
Chengxing
C
Department of Oral and Maxillofacial Surgery, Xiang Ya Hospital, Central Southern University, Changsha 410078, China.
Ai
Midan
M
Ren
Wei
W
Xiao
Hui
H
Li
Xiaoyan
X
Tang
Faqing
F
Gu
Huanhua
H
Yi
Wei
W
Weng
Xinxian
X
Deng
Xiyun
X
Cao
Ya
Y
D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000502:physiology*; D009303:Nasopharyngeal Neoplasms / Q000503:physiopathology*; D014176:Protein Biosynthesis; D015398:Signal Transduction / Q000502:physiology*; D047990:TNF Receptor-Associated Factor 1; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000502:physiology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D047990:TNF Receptor-Associated Factor 1; D014763:Viral Matrix Proteins