Regulation of hepatocyte nuclear factor 1 activity by wild-type and mutant hepatitis B virus X proteins.

Abstract

The hepatitis B virus (HBV) core promoter regulates the transcription of two related RNA products named precore RNA and core RNA. Previous studies indicate that a double-nucleotide mutation that occurs frequently during chronic HBV infection converts a nuclear receptor binding site in the core promoter to the binding site of the transcription factor hepatocyte nuclear factor-1 (HNF-1) and specifically suppresses the transcription of the precore RNA. This mutation also changes two codons in the overlapping X protein coding sequence. In this report, we demonstrate that the X protein and its mutant X(mt) can physically bind to HNF-1 both in vitro and in vivo. Further analyses indicate that both X and X(mt) can enhance the gene transactivation and the DNA binding activities of HNF-1. This finding demonstrates for the first time that the X protein can stimulate the DNA binding activity of a homeodomain transcription factor. Interestingly, while both X and X(mt) can stimulate the HNF-1 activities, they differ in their effects: a smaller amount of X(mt) is needed to generate greater transactivation and DNA binding activities of HNF-1. This functional difference between X and X(mt) may have important implications in HBV pathogenesis and is apparently why they have different effects on the core promoter bearing the HNF-1 binding site.

• Authors: Jie Li, Zhenming Xu, Yanyan Zheng, Deborah L Johnson, Jing-Hsiung Ou
• Journal: Journal of virology (J Virol) Vol. 76 Issue 12 Pg. 5875-81 (Jun 2002) ISSN: 0022-538X [Print] United States
• PMID: 12021320 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Viral
• DNA-Binding Proteins
• HNF1A protein, human
• HNF1B protein, human
• Hepatocyte Nuclear Factor 1-alpha
• Nuclear Proteins
• Protein Precursors
• Trans-Activators
• Transcription Factors
• Viral Core Proteins
• Viral Regulatory and Accessory Proteins
• hepatitis B virus X protein
• Hepatocyte Nuclear Factor 1
• Hepatocyte Nuclear Factor 1-beta

Topics

• Binding Sites
• Carcinoma, Hepatocellular
• DNA, Viral (metabolism)
• DNA-Binding Proteins
• Gene Expression Regulation
• Hepatitis B virus (genetics, metabolism)
• Hepatocyte Nuclear Factor 1
• Hepatocyte Nuclear Factor 1-alpha
• Hepatocyte Nuclear Factor 1-beta
• Humans
• Mutation
• Nuclear Proteins
• Plasmids (genetics)
• Precipitin Tests
• Protein Precursors (genetics, metabolism)
• Trans-Activators (genetics, metabolism)
• Transcription Factors (genetics, metabolism)
• Transfection
• Tumor Cells, Cultured
• Viral Core Proteins (genetics, metabolism)
• Viral Regulatory and Accessory Proteins