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Characterization of a strong repression domain in the hinge region of orphan nuclear receptor hB1F/hLRH-1.
- Source :
-
Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica [Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai)] 2003 Oct; Vol. 35 (10), pp. 909-16. - Publication Year :
- 2003
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Abstract
- Human hepatitis B virus enhancer II B1 binding factor (hB1F also known as NR5A2, LRH-1, FTF or CPF) is an orphan nuclear receptor and belongs to the fushi tarazu factor I (FTZ-F1) subfamily. It plays important roles in the transcriptional regulation of a number of genes involved in bile acid biosynthesis pathway, hepatitis B virus (HBV) replication and liver specific regulatory network. Like other nuclear receptors, hB1F is composed of modular functional domains. We characterized a domain in its hinge region that imposes a strong repression on the transcriptional activity of hB1F, which is important for the function of hB1F on regulating the activity of HBV enhancer II/core promoter. Mutations of the core residues in this domain abrogate the repression. Bioinformatic analysis reveals that the amino acid sequence of this region is highly conserved only among members of the FTZ-F1 subfamily. The repression is observed in five cell lines tested, while the degree of the repression varies greatly, which does not parallel with the expression level of the DEAD box protein of 130 kD (DP103), a potential interacting protein of a homologous domain in the steroidogenic factor 1 (SF-1). Moreover, the repression is not affected by the silencing mediator for retinoic acid receptor and thyroid hormone receptor (SMRT) and steroid receptor coactivator 1 (SRC-1). Collectively, these data suggest a novel regulatory mechanism for the transcriptional activity of hB1F.
- Subjects :
- Amino Acid Sequence
Animals
Binding Sites genetics
Blotting, Western
COS Cells
Cell Line, Tumor
Chlorocebus aethiops
Computational Biology methods
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Gene Expression Regulation genetics
HeLa Cells
Histone Acetyltransferases
Humans
Luciferases genetics
Luciferases metabolism
Molecular Sequence Data
Nuclear Receptor Co-Repressor 2
Nuclear Receptor Coactivator 1
Point Mutation
Receptors, Cytoplasmic and Nuclear genetics
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Repressor Proteins genetics
Repressor Proteins metabolism
Sequence Homology, Amino Acid
Steroidogenic Factor 1
Trans-Activators genetics
Transcription Factors genetics
Transcription Factors metabolism
Receptors, Cytoplasmic and Nuclear metabolism
Trans-Activators metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0582-9879
- Volume :
- 35
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica
- Publication Type :
- Academic Journal
- Accession number :
- 14515208