Hepatitis B virus X protein (HBx) induces G2/M arrest and apoptosis through sustained activation of cyclin B1-CDK1 kinase.
Hepatitis B virus X protein (HBx) is a multi-functional regulatory protein that is known to be involved in viral proliferation, transcriptional activation and cell growth control. However, the actual role of HBx in cell growth control remains controversial. In this study, the impact of HBx on cell growth in vitro and in vivo was further investigated. HBx was able to inhibit the growth of hepatocellular carcinoma (HCC) cells and induce G2/M arrest in vitro. Moreover, unlike many other G2/M arrest mechanisms, HBx did not inhibit cyclin B1-CDK1 kinase activity, but it persistently activated the cyclin B1-CDK1 kinase. In vivo, HBx inhibited tumor cell growth and induced apoptosis as well as inhibited the growth of vascular endothelial cells. In conclusion, HBx induced G2/M arrest and apoptosis through sustained activation of cyclin B1-CDK1 kinase, and negatively regulated cell growth in vitro and in vivo.
Cheng
Ping
P
State Key Laboratory of Biotherapy, West China Hospital, School of Life Science, Sichuan University, Sichuan 610041, PR China.
Li
Yuhua
Y
Yang
Liping
L
Wen
Yanjun
Y
Shi
Wei
W
Mao
Yongqiu
Y
Chen
Ping
P
Lv
Huimin
H
Tang
Qingqing
Q
Wei
Yuquan
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D002455:Cell Division; D049109:Cell Proliferation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D056744:Cyclin B1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016195:G2 Phase; D006801:Humans; D007124:Immunoenzyme Techniques; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D015534:Trans-Activators / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
D056744:Cyclin B1; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D016203:CDC2 Protein Kinase