Hepatitis B virus X protein induced expression of the Nur77 gene.
Hepatitis B virus (HBV) X protein (HBx) plays an essential role in development of HBV-associated hepatocellular carcinoma (HCC). Recently, we reported that HBx induces Fas Ligand (FasL) expression, which may help HCC cells to evade host-immune surveillance. The aim of this study was to investigate the role of HBx in expression of Nur77, an orphan nuclear receptor implicated in the upregulation of FasL. When Chang X-34 expressing HBx under the control of a doxycycline-inducible promoter was examined, induction of Nur77 was observed following HBx expression. Blocking of Nur77 function by introduction of an antisense or a dominant negative mutant Nur77 significantly inhibited the induction of FasL, indicating that Nur77 plays critical roles in FasL expression. Further, a high-level expression of transcripts and DNA binding of Nur77 were observed in the HBV-integrated cell lines established from HCC patients that express HBx. These results suggested that Nur77 may contribute to leading the HBx-induced Fas/FasL signaling pathway which eliminates invading Fas-expressing lymphocytes.
Lee
M O
MO
Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Korea. molee@sejong.ac.kr
Kang
H J
HJ
Cho
H
H
Shin
E C
EC
Park
J H
JH
Kim
S J
SJ
D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D053222:Fas Ligand Protein; D006509:Hepatitis B / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009154:Mutation; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins; D016662:Virus Integration
D004268:DNA-Binding Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein