Hepatitis B virus regulation of Raf1 promoter activity through activation of transcription factor AP-2α

Hepatitis B virus regulation of Raf1 promoter activity through activation of transcription factor... The X protein of hepatitis B virus (HBx) is one of the important factors in the development of hepatocellular carcinoma. Raf1 kinase is a central component of many signaling pathways that are involved in normal cell growth and oncogenic transformation. We previously demonstrated that hepatitis B virus regulates Raf1 expression in HepG2.2.15 cells by enhancing its promoter activity and that HBx and HBs might play an important role in this process. However, the underlying molecular mechanisms remain unclear. In this study, we show that nucleotides −209 to −133 of the Raf1 promoter sequence constitute the core region where hepatitis B virus is regulated. This regulation was found to require the involvement of cis-regulatory element AP-2α. We further demonstrated that AP-2α expression was higher in HepG2.2.15 cells (HBV-expressing cells) than in HepG2 cells in vitro . Silencing AP-2α expression by siRNA significantly inhibited the Raf1 promoter activity in HepG2.2.15 cells. These findings indicated that HBV regulates Raf1 promoter activity, possibly through AP-2α. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Hepatitis B virus regulation of Raf1 promoter activity through activation of transcription factor AP-2α

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Publisher
Springer Vienna
Copyright
Copyright © 2013 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-012-1561-y
Publisher site
See Article on Publisher Site

Abstract

The X protein of hepatitis B virus (HBx) is one of the important factors in the development of hepatocellular carcinoma. Raf1 kinase is a central component of many signaling pathways that are involved in normal cell growth and oncogenic transformation. We previously demonstrated that hepatitis B virus regulates Raf1 expression in HepG2.2.15 cells by enhancing its promoter activity and that HBx and HBs might play an important role in this process. However, the underlying molecular mechanisms remain unclear. In this study, we show that nucleotides −209 to −133 of the Raf1 promoter sequence constitute the core region where hepatitis B virus is regulated. This regulation was found to require the involvement of cis-regulatory element AP-2α. We further demonstrated that AP-2α expression was higher in HepG2.2.15 cells (HBV-expressing cells) than in HepG2 cells in vitro . Silencing AP-2α expression by siRNA significantly inhibited the Raf1 promoter activity in HepG2.2.15 cells. These findings indicated that HBV regulates Raf1 promoter activity, possibly through AP-2α.

Journal

Archives of VirologySpringer Journals

Published: Apr 1, 2013

References

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