Hepatitis B virus X protein ; Peroxisome proliferator-activated receptor γ ; Transactivation ; Protein–protein interaction ; PPARγ, peroxisome proliferator-activated receptor γ ; HCC, hepatocellular carcinoma ; HBx, hepatitis B virus X protein ; HBV, hepatitis B virus ; RXR, retinoid X receptor ; PPRE, peroxisome proliferator response element ; HBx-TG, hepatitis B virus X protein transgenic ; EMSA, electrophoretic mobility shift assay ; HA, hemagglutinin ; NE, nuclear extract ; DBD, DNA binding domain ; LBD, ligand binding domain ; NLS, nuclear localization signal ; IFA, immunofluorescence assay ; rHBx, recombinant hepatitis B virus X protein
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.