Epstein-Barr virus encoded latent membrane protein 1 modulates nuclear translocation of telomerase reverse transcriptase protein by activating nuclear factor-kappaB p65 in human nasopharyngeal carcinoma cells.
Sustained proliferation of cancer cells requires that telomerase maintain chromosomal stability and prolong telomere length-regulated cell replication. Human telomerase reverse transcriptase (hTERT), the human telomerase catalytic subunit, and also the key determinant of the enzymatic activity of human telomerase, is regulated both at the transcriptional level and via phosphorylation and translocation. In this study, we show that latent membrane protein 1 (LMP1), the principal oncoprotein of Epstein-Barr virus (EBV), modulates telomerase activity by inducing the direct binding of hTERT to nuclear factor kappaB (NF-kappaB) p65 and translocation of both proteins from the cytoplasm to the nucleus in nasopharyngeal carcinoma cells (NPC). Conversely, a NF-kappaB nuclear translocation inhibitor, (benzylcarbonyl)-Leu-Leu-phenylalaninal (Z-LLF-CHO), and a dominant negative mutant of inhibitor of NFkappaB (IkappaBalpha), can block LMP1-induced hTERT nuclear translocation. These studies suggest a novel function of LMP1 and confirm that NF-kappaB plays an important role in regulating the activation and nuclear translocation of telomerase in NPC cells.
Ding
Lin
L
Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan, China. ycao98@public.cs.hn.cn
Li
Li Li
LL
Yang
Jing
J
Tao
Yong Guang
YG
Ye
Mao
M
Shi
Ying
Y
Tang
Min
M
Yi
Wei
W
Li
Xiao Lan
XL
Gong
Jian Ping
JP
Cao
Ya
Y
D000956:Antigens, Viral / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D021381:Protein Transport; D019098:Telomerase / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000494:pharmacology*
D000956:Antigens, Viral; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014763:Viral Matrix Proteins; D000072000:NF-KappaB Inhibitor alpha; D019098:Telomerase