Macrophage migration inhibitory factor interacts with HBx and inhibits its apoptotic activity.
HBx, a transcriptional transactivating protein of hepatitis B virus (HBV), is required for viral infection and has been implicated in virus-mediated liver oncogenesis. However, the precise molecular mechanism remains largely elusive. We used the yeast two-hybrid system to identify that HBx interacts with MIF directly. Macrophage migration inhibitory factor (MIF) is implicated in the regulation of inflammation, cell growth, and even tumor formation. The interaction between HBx and MIF was verified with co-immunoprecipitation, GST pull-down, and cellular colocalization. The expression of MIF was up-regulated in HBV particle producing cell 2.2.15 compared with HepG2 cell. Both HBx and MIF cause HepG2 cell G(0)/G(1) phase arrest, proliferation inhibition, and apoptosis. However, MIF can counteract the apoptotic effect of HBx. These results may provide evidence to explain the link between HBV infection and hepatocellular carcinoma.
Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing 100850, PR China.
Shimeng
S
Zhang
Ruxian
R
Lin
Zhe
Z
Zhou
Siyuan
S
Wen
Li
L
Lin
Suhong
S
Chen
Yajun
Y
Shan
Yuwen
Y
Cong
Shengqi
S
Wang
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000502:physiology*; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
D006131:Growth Inhibitors; D008263:Macrophage Migration-Inhibitory Factors; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein