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

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] 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