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

Youn Hee Choi, Ha Il Kim, Je Kyung Seong, Dae Yeul Yu, Hyeseong Cho, Mi Ock Lee, Jae Myun Lee, Yong Ho Ahn, Se Jong Kim, Jeon Han Park

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Ligand activation of peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ activation has not been characterized in hepatitis B virus (HBV)-associated HCC. Herein, we demonstrated that HBx counteracted growth inhibition caused by PPARγ ligand in HBx-associated HCC cells. We found that HBx bound to DNA binding domain of PPARγ and HBx/PPARγ interaction blocked nuclear localization and binding to recognition site of PPARγ. HBx significantly suppressed a PPARγ-mediated transactivation. These results suggest that HBx modulates PPARγ function through protein-protein interaction.

Original languageEnglish
Pages (from-to)73-80
Number of pages8
JournalFEBS Letters
Volume557
Issue number1-3
DOIs
StatePublished - 16 Jan 2004

Bibliographical note

Funding Information:
We thank Drs. Ronald M. Evans, David J. Mangelsdof, and Heonjoong Kang for providing us with PPRE 3 -tk-LUC and pCMX-mPPARγ and Sankyo Co. Ltd for the troglitazone. This work was supported by a grant from the Korean National Cancer Control Program, Ministry of Health and Welfare, South Korea (02-1-2-0590).

Keywords

  • Hepatitis B virus X protein
  • Peroxisome proliferator-activated receptor γ
  • Protein-protein interaction
  • Transactivation

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