Hepatitis B virus X protein sensitizes UV-induced apoptosis by transcriptional transactivation of Fas ligand gene expression.
Hepatitis B virus X protein (HBx) is a promiscuous transcriptional transactivator of many viral and cellular promoters. HBx plays an important role in hepatitis B virus pathogenesis related with liver diseases including hepatocellular carcinoma (HCC). HBx is also involved in the signal transduction and the apoptosis of HBV-infected cells. However, the exact mechanism of apoptosis by HBx is still controversial. To demonstrate the mechanism of apoptosis by HBx, we induced the apoptosis of HBx-expressing liver cells, HepG2-X, by UV irradiation. We found that HepG2-X was much more sensitive to the UV-induced apoptosis than normal liver cells by analyzing the DNA fragmentation and the cell viability. Very interestingly, when the Fas-associated death domain (FADD)-dominant negative mutant protein was present in HepG2-X, the sensitized apoptotic response of HepG2-X to UV was completely abolished suggesting that there is a close relationship between HBx and Fas pathway in apoptosis. Therefore we examined the transactivation of Fas receptor (Fas) promoter and Fas ligand (FasL) promoter by HBx. We found that HBx strongly transcriptionally transactivated FasL promoter, but not Fas promoter. In addition, it also turned out that the mRNA levels of FasL are higher than those of Fas in HepG2-X. Taken together, HBx sensitizes the apoptosis of UV-irradiated liver cells by transcriptional transactivation of FasL gene.
Kim
Sang Yong
SY
Department of Microbiology, School of Bioscience and Biotechnology, Chungnam National University, Daejeon, Korea.
Kim
Jeong Ki
JK
Kim
Hye Jin
HJ
Ahn
Jeong Keun
JK
D017209:Apoptosis / Q000528:radiation effects*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D002470:Cell Survival; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis; D053222:Fas Ligand Protein; D017930:Genes, Reporter; D022781:Hepatocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D008024:Ligands; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D054334:Viral Regulatory and Accessory Proteins
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D048069:Tumor Necrosis Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D015500:Chloramphenicol O-Acetyltransferase