Hepatitis B virus X protein modulates peroxisome proliferator-activated receptor gamma through protein-protein interaction.
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.
Choi
Youn-Hee
YH
Department of Microbiology and Brain Korea 21 Project of Medical Sciences, Institute for Immunology and Immunological Diseases, Seoul, South Korea.
Kim
Ha-il
HI
Seong
Je Kyung
JK
Yu
Dae-Yeul
DY
Cho
Hyeseong
H
Lee
Mi-Ock
MO
Lee
Jae Myun
JM
Ahn
Yong-ho
YH
Kim
Se Jong
SJ
Park
Jeon Han
JH
D000256:Adenoviridae; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000821:virology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017931:DNA Primers; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006511:Hepatitis B Antigens / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008113:Liver Neoplasms / Q000473:pathology / Q000821:virology; D008164:Luminescent Proteins / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014157:Transcription Factors / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins
D017931:DNA Primers; D006511:Hepatitis B Antigens; D008024:Ligands; D008164:Luminescent Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D049452:Green Fluorescent Proteins