Epstein-Barr virus encoded latent membrane protein 1 modulates nuclear translocation of telomerase reverse transcriptase protein by activating nuclear factor-κB p65 in human nasopharyngeal carcinoma cells

Lin Ding, Li Li Li, Jing Yang, Guang Tao Yong, Mao Ye, Ying Shi, Min Tang, Wei Yi, Lan Li Xiao, Ping Gong Jian, Ya Cao

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

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 κB (NF-κB) p65 and translocation of both proteins from the cytoplasm to the nucleus in nasopharyngeal carcinoma cells (NPC). Conversely, a NF-κB nuclear translocation inhibitor, (benzylcarbonyl)-Leu-Leu- phenylalaninal (Z-LLF-CHO), and a dominant negative mutant of inhibitor of NFκB (IκBα), can block LMP1-induced hTERT nuclear translocation. These studies suggest a novel function of LMP1 and confirm that NF-κB plays an important role in regulating the activation and nuclear translocation of telomerase in NPC cells.

Original languageEnglish (US)
Pages (from-to)1881-1889
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume37
Issue number9
DOIs
StatePublished - Sep 2005

Keywords

  • Epstein-Barr virus
  • Latent membrane protein 1
  • Nasopharyngeal carcinoma
  • Nuclear factor κB
  • Nuclear translocation
  • Telomerase
  • hTERT

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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