Latent membrane protein 1 encoded by Epstein-Barr virus modulates directly and synchronously cyclin D1 and p16 by newly forming a c-Jun/Jun B heterodimer in nasopharyngeal carcinoma cell line

Virus Res. 2005 Nov;113(2):89-99. doi: 10.1016/j.virusres.2005.04.019.

Abstract

Recently we confirmed that latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) accelerates a newly forming active c-Jun/Jun B heterodimer, a transcription factor, but little is known about the target gene regulated by it. In this paper, results indicated that a c-Jun/Jun B heterodimer induced by LMP1 upregulated cyclin D1 promoters activity and expression, on the contrary, downregulated p16, and maladjustment of cyclin D1 and p16 expression accelerated progression of cell cycle. Firstly, we found a c-Jun/Jun B heterodimer regulated synchronously and directly cyclin D1 and p16 in the Tet-on-LMP1-HNE2 cell line, in which LMP1 expression is regulated by Tet-on system. This paper investigated in depth function of the newly forming active c-Jun/Jun B heterodimer, and built new connection between environmental pathogenic factor, signal transduction and cell cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / metabolism
  • Carcinoma / virology
  • Cell Cycle
  • Cell Line
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Dimerization
  • Doxycycline / pharmacology
  • Humans
  • Nasopharyngeal Neoplasms / metabolism
  • Promoter Regions, Genetic / physiology
  • Protein Binding
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Signal Transduction
  • Transfection
  • Viral Matrix Proteins / metabolism*

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Proto-Oncogene Proteins c-jun
  • Viral Matrix Proteins
  • Cyclin D1
  • Doxycycline