Hepatitis B virus X protein regulates

liver411

HEPATOLOGY
November 2003 . Volume 38 . Number 5
Original Articles: Viral Hepatitis

Hepatitis B virus X protein regulates transactivation activity and protein
stability of the cancer-amplified transcription coactivator ASC-2

Hee Jeong Kong1 ,Min Jung Park1 ,SunHwa Hong1 [MEDLINE LOOKUP]
Hyun Jung Yu1 ,Young Chul Lee2 ,Young Hyun Choi3 ,JaeHun Cheong1

   Abstract
Hepatitis B virus X protein (HBx) is a transcriptional coactivator that
plays a significant role in the regulation of genes involved in inflammation
and cell survival. A recently identified cellular coactivator, activating
signal cointegrator 2 (ASC-2), is enriched in liver cancer cells and
associates with many transcription factors that are active in hepatocytes.
The tissue colocalization of these 2 proteins, in view of their similar
regulatory functions, led us to examine whether HBx and ASC-2 cooperate in
transcriptional activation of gene expression. Glutathione S-transferase
(GST) pull-down assays and mammalian 2-hybrid analysis show that the
transactivation domain of HBx interacts with the C-terminal domain of ASC-2.
In fact, these 2 proteins associated in a ternary complex that included the
transcriptional activator retinoid X receptor (RXR). Mechanistically, on
expression of HBx, the half-life of the ASC-2 coactivator is observed to
increase in concordance with the observed increase in ASC-2-dependent
coactivation of transcription. In conclusion, these results show that HBx
stabilizes the cellular coactivator ASC-2 through direct protein-protein
interaction, affecting the regulation of genes actively transcribed in liver
cancer cells. (HEPATOLOGY 2003;38:1258-1266.)


   Publishing and Reprint Information
From the 1Department of Molecular Biology, Pusan National University, Busan;
2Hormone Research Center, Chonnam National University, Kwangju; and
3Department of Biochemistry, College of Oriental Medicine, Dong-Eui
University, Busan, Korea.
Received July 12, 2002.
Accepted August 1, 2003.
Supported by a grant from the Korea Health Ministry of Health and Welfare,
Republic of Korea (01-PJ1-PG3-20900-0098).
Address reprint requests to: JaeHun Cheong, Ph.D., Department of Molecular
Biology, Pusan National University, Busan, 609-735, Korea. E-mail:
[email protected] ; fax: (82) 51-513-9258.
Copyright © 2003 by the American Association for the Study of Liver
Diseases.
0270-9139/03/3805-0024$30.00/0
doi:10.1053/jhep.2003.50451