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

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.

• Authors: Hee Jeong Kong, Min Jung Park, SunHwa Hong, Hyun Jung Yu, Young Chul Lee, Young Hyun Choi, JaeHun Cheong
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 38 Issue 5 Pg. 1258-66 (Nov 2003) ISSN: 0270-9139 [Print] United States
• PMID: 14578865 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intracellular Signaling Peptides and Proteins
• NCOA6 protein, human
• Nuclear Receptor Coactivators
• Receptors, Retinoic Acid
• Retinoid X Receptors
• Trans-Activators
• Transcription Factor AP-1
• Transcription Factors
• Viral Regulatory and Accessory Proteins
• hepatitis B virus X protein

Topics

• Cell Line, Tumor
• Drug Interactions
• Drug Stability
• Drug Synergism
• Half-Life
• HeLa Cells
• Humans
• Intracellular Signaling Peptides and Proteins
• Nuclear Receptor Coactivators
• Protein Structure, Tertiary (physiology)
• Receptors, Retinoic Acid (genetics, metabolism)
• Retinoid X Receptors
• Trans-Activators (metabolism, pharmacology, physiology)
• Transcription Factor AP-1 (genetics)
• Transcription Factors (chemistry, genetics, metabolism, pharmacology)
• Transcriptional Activation (drug effects, physiology)
• Transfection
• Viral Regulatory and Accessory Proteins