Epstein-Barr virus latent membrane protein 1 (LMP1) up-regulates Id1 expression in nasopharyngeal epithelial cells

Research output: Contribution to journalArticle

Authors

  • HM Li
  • Z Zhuang
  • Q Wang
  • X Wang
  • HL Wong
  • H Feng
  • D Jin
  • MT Ling
  • YC Wong
  • D Huang
  • SW Tsao

Colleges, School and Institutes

Abstract

Nasopharyngeal carcinoma is closely associated with Epstein-Barr virus (EBV) infection. The EBV-encoded LMP1 has cell transformation property. It suppresses cellular senescence and enhances cell survival in various cell types. Many of the downstream events of LMP1 expression are mediated through its ability to activate NF-kappaB. In this study, we report a novel function of LMP1 to induce Id1 expression in nasopharyngeal epithelial cells (NP69) and human embryonal kidney cells (HEK293). The Id1 is a basic helix-loop-helix (bHLH) protein and a negative transcriptional regulator of p16(INK4a). Expression of Id1 facilitates cellular immortalization and stimulates cell proliferation. With the combination of both specific chemical inhibitors and genetic inhibitors of cell signaling, we showed that induction of Id1 by LMP1 was dependent on its NF-kappaB activation domain at the carboxy-terminal region, CTAR1 and CTAR2. Induction of Id1 by LMP1 may facilitate clonal expansion of premalignant nasopharyngeal epithelial cells infected with EBV and may promote their malignant transformation.

Details

Original languageEnglish
Pages (from-to)4488-4494
Number of pages7
JournalOncogene
Volume23
Early online date5 Apr 2004
Publication statusPublished - 5 Apr 2004

Keywords

  • LMP1, Epstein-Barr virus, nasopharyngeal carcinoma, nuclear factor kappa B, Id1