Hepatitis B virus X protein modulates peroxisome proliferator-activated receptor gamma through protein-protein interaction

FEBS Lett. 2004 Jan 16;557(1-3):73-80. doi: 10.1016/s0014-5793(03)01449-2.

Abstract

Ligand activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been reported to induce growth inhibition and apoptosis in various cancers including hepatocellular carcinoma (HCC). However, the effect of hepatitis B virus X protein (HBx) on PPARgamma activation has not been characterized in hepatitis B virus (HBV)-associated HCC. Herein, we demonstrated that HBx counteracted growth inhibition caused by PPARgamma ligand in HBx-associated HCC cells. We found that HBx bound to DNA binding domain of PPARgamma and HBx/PPARgamma interaction blocked nuclear localization and binding to recognition site of PPARgamma. HBx significantly suppressed a PPARgamma-mediated transactivation. These results suggest that HBx modulates PPARgamma function through protein-protein interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Apoptosis / drug effects
  • Base Sequence
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • Cell Division / drug effects
  • Cell Line
  • DNA Primers
  • Genes, Reporter
  • Genetic Vectors
  • Green Fluorescent Proteins
  • Hepatitis B Antigens / chemistry
  • Hepatitis B Antigens / pharmacology
  • Humans
  • Ligands
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Luminescent Proteins / genetics
  • Protein Transport / drug effects
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / drug effects
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / drug effects
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism
  • Trans-Activators / pharmacology*
  • Transcription Factors / chemistry
  • Transcription Factors / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Tumor Cells, Cultured
  • Viral Regulatory and Accessory Proteins

Substances

  • DNA Primers
  • Hepatitis B Antigens
  • Ligands
  • Luminescent Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
  • Green Fluorescent Proteins