Dual effects of hepatitis B virus X protein on the regulation of cell-cycle control depending on the status of cellular p53.
Despite the extensive studies on the roles of hepatitis B virus (HBV) X protein (HBx) in the development of hepatocellular carcinomas (HCCs), the mechanisms by which HBx contributes to HCC remain controversial. In this study, the effect of HBx on the G(1)-S checkpoint control depending on the status of p53 was compared. Transcription of p21(waf1/cip1) was activated by HBx in the presence of functional p53 in a dose-dependent manner. However, it was repressed by HBx when p53 was absent or present at a low level. Furthermore, the growth rate of the HBx-expressing NIH3T3 cell lines compared with that of the parental cells was decreased when p53 was upregulated by a DNA-damaging agent, cisplatin, whereas it increased approximately twofold when p53 was present at a very low level. Thus, the opposite effects of HBx on the regulation of the cell cycle depending on the status of p53 might be important to understand the progression of hepatic diseases in HBV-positive patients.
Ahn
Ji Young
JY
Department of Microbiology, College of Natural Sciences, Pusan National University, Pusan 609-735, Korea1.
Jung
Eun Young
EY
Department of Microbiology, College of Natural Sciences, Pusan National University, Pusan 609-735, Korea1.
Kwun
Hyun Jin
HJ
Department of Microbiology, College of Natural Sciences, Pusan National University, Pusan 609-735, Korea1.
Lee
Chang-Woo
CW
Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea2.
Sung
Young-Chul
YC
Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea2.
Jang
Kyung Lib
KL
Department of Microbiology, College of Natural Sciences, Pusan National University, Pusan 609-735, Korea1.
D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D005786:Gene Expression Regulation; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D051379:Mice; D012097:Repressor Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012097:Repressor Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein