Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P19793 (retinoid X receptor alpha)
 391 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatitis B virus enhancer 1 contains a retinoic acid responsive element (RARE). We have previously demonstrated that retinoid X receptor alpha (RXR alpha) transactivates enhancer 1 by binding to the RARE. The present study has revealed that a heterodimeric complex composed of RXR alpha and peroxisome proliferator-activated receptor (PPAR) interacts with the hepatitis B virus RARE. Transient transfection studies, in conjunction with in vitro DNA binding data, support the hypothesis that the RXR alpha-PPAR heterodimer transactivates enhancer 1.
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PMID:Retinoid X receptor alpha transactivates the hepatitis B virus enhancer 1 element by forming a heterodimeric complex with the peroxisome proliferator-activated receptor. 798 54

Hepatitis B virus (HBV) enhancer I has been shown to consist of several cis-acting sequences for the HBV gene expression efficiently in certain types of cells. Transcriptional regulation of HBV X gene mediated by enhancer I might be one of the mechanisms by which HBV obtains hepatotropism. By mutagenesis analysis of enhancer I function in the enhancer I/X gene promoter complex, we characterized a specific transcriptional regulatory region (designated as a LSR element, nt 989-1030) of enhancer I for the X gene promoter by means of the transient transfection technique using hepatic and nonhepatic cells. Based on the analysis of protein factors interacting with the LSR element, liver-enriched transcriptional factors, HNF3 and HNF4 or retinoid X receptor alpha (RXR alpha), are probably implicated in the activity of enhancer I for the efficient expression of X gene through their interaction with the LSR element in the hepatic cell. Furthermore, the isolated LSR element was demonstrated to function alone as a specific cis-acting element and to be able to activate transcription from the X gene promoter efficiently in the hepatic cell in an orientation-independent manner.
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PMID:Characterization of a specific region in the hepatitis B virus enhancer I for the efficient expression of X gene in the hepatic cell. 932 35

Hepatotropism is a prominent feature of hepatitis B virus (HBV) infection. Cell lines of nonhepatic origin do not independently support HBV replication. Here, we show that the nuclear hormone receptors, hepatocyte nuclear factor 4 and retinoid X receptor alpha plus peroxisome proliferator-activated receptor alpha, support HBV replication in nonhepatic cells by controlling pregenomic RNA synthesis, indicating these liver-enriched transcription factors control a unique molecular switch restricting viral tropism. In contrast, hepatocyte nuclear factor 3 antagonizes nuclear hormone receptor-mediated viral replication, demonstrating distinct regulatory roles for these liver-enriched transcription factors.
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PMID:Transcriptional regulation of hepatitis B virus by nuclear hormone receptors is a critical determinant of viral tropism. 1117 38

A natural hepatitis B virus (HBV) variant associated with seroconversion from HBeAg to anti-HBe antibody contains two nucleotide substitutions (A1764T and G1766A) in the proximal nuclear hormone receptor binding site in the nucleocapsid promoter. These nucleotide substitutions prevent the binding of the retinoid X receptor alpha (RXR alpha)-peroxisome proliferator-activated receptor alpha (PPAR alpha) heterodimer without greatly altering the efficiency of binding of hepatocyte nuclear factor 4 (HNF4) to this recognition sequence. In addition, these nucleotide substitutions create a new binding site for HNF1. Analysis of HBV transcription and replication in nonhepatoma cells indicates that RXR alpha-PPAR alpha heterodimers support higher levels of pregenomic RNA transcription from the wild-type than from the variant nucleocapsid promoter, producing higher levels of wild-type than of variant replication intermediates. In contrast, HNF4 supports higher levels of pregenomic RNA transcription from the variant than from the wild-type nucleocapsid promoter, producing higher levels of variant than of wild-type replication intermediates. HNF1 can support variant virus replication at a low level but is unable to support replication of the wild-type HBV genome. These observations indicate that the replication of wild-type and variant viruses can be differentially regulated by the liver-specific transcription factors that bind to the proximal nuclear hormone receptor binding site of the nucleocapsid promoter. Differential regulation of viral replication may be important in the selection of specific viral variants as a result of an antiviral immune response.
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PMID:Replication of the wild type and a natural hepatitis B virus nucleocapsid promoter variant is differentially regulated by nuclear hormone receptors in cell culture. 1153 57

A hepatitis B virus (HBV) transgenic mouse containing a naturally occurring mutation in the nucleocapsid promoter (A1764T plus G1766A) that inhibits the retinoid X receptor alpha (RXRalpha) plus peroxisome proliferator-activated receptor alpha (PPARalpha) heterodimer from binding to the proximal nuclear hormone receptor recognition sequence has been generated. Viral transcription and replication occur in the liver and kidney. The nucleocapsid promoter mutation does not prevent peroxisome proliferators from increasing viral transcription and replication in the liver of these variant HBV transgenic mice. This suggests that peroxisome proliferators may enhance viral transcription directly in a PPARalpha-dependent manner through the nuclear hormone receptor recognition site in the enhancer 1 region of the HBV genome. Hepatocyte nuclear factor 4 (HNF4) binding to the proximal nuclear hormone receptor recognition sequence in the nucleocapsid promoter appears to limit RNA synthesis from the precore transcription initiation site. Consequently, the variant HBV transgenic mice transcribe very little precore RNA and secrete extremely low levels of hepatitis B e antigen (HBeAg) compared with the wild-type HBV transgenic mice. This is consistent with the suggestion that viruses expressing HBeAg are preferentially eliminated in infected individuals when they seroconvert from HBeAg positive to anti-HBe antibody-positive status, leaving escape HBV variants that have reduced HBeAg expression.
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PMID:Transcription and replication of a natural hepatitis B virus nucleocapsid promoter variant is regulated in vivo by peroxisome proliferators. 1168 47

Hepadnavirus replication occurs in hepatocytes in vivo and in hepatoma cell lines in cell culture. Hepatitis B virus (HBV) replication can occur in nonhepatoma cells when pregenomic RNA synthesis from viral DNA is activated by the expression of the nuclear hormone receptors hepatocyte nuclear factor 4 (HNF4) and the retinoid X receptor alpha (RXR alpha) plus peroxisome proliferator-activated receptor alpha (PPAR alpha) heterodimer. Nuclear hormone receptor-dependent HBV replication is inhibited by hepatocyte nuclear factor 3 (HNF3). In contrast, HNF3 and HNF4 support duck hepatitis B virus (DHBV) replication in nonhepatoma cells, whereas the RXR alpha-PPAR alpha heterodimer inhibits HNF4-dependent DHBV replication. HNF3 and HNF4 synergistically activate DHBV pregenomic RNA synthesis and viral replication. The conditions that support HBV or DHBV replication in nonhepatoma cells are not able to support woodchuck hepatitis virus replication. These observations indicate that avian and mammalian hepadnaviruses have distinct transcription factor requirements for viral replication.
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PMID:Avian and Mammalian hepadnaviruses have distinct transcription factor requirements for viral replication. 1209 59

Previous studies of human hepatitis B virus (HBV) transcription revealed the requirement of two enhancer elements. Enhancer I (EnhI) is located upstream of the X promoter and is targeted by multiple activators, including basic leucine zipper proteins, and enhancer II (EnhII) is located upstream to the PreCore promoter and is targeted mainly by nuclear receptors (NRs). The mode of interplay between these enhancers and their unique contributions in regulating HBV transcription remained obscure. By using time course analysis we revealed that the HBV transcripts are categorized into early and late groups. Chang (CCL-13) cells are impaired in expression of the late transcripts. This could be corrected by overexpressing EnhII activators, such as hepatocyte nuclear factor 4 alpha, the retinoid X receptor alpha, and the peroxisome proliferator-activated receptor alpha, suggesting that in Chang cells EnhI but not EnhII is active. Replacing the 5'-end EnhI sequence with a synthetic Gal4 response (UAS) DNA fragment ceased the production of the early transcripts. Under this condition NR overexpression poorly activated EnhII. However, activation of the UAS by Gal4-p53 restored both the expression of the early transcripts and the EnhII response to NRs. Thus, a functional EnhI is required for activation of EnhII. We found a major difference between Gal4-p53 and Gal4-VP16 behavior. Gal4-p53 activated the early transcripts, while Gal4-VP16 inhibited the early transcripts but activated the late transcripts. These findings indicate that the composition of the EnhI binding proteins may play a role in early to late switching. Our data provides strong evidence for the role of EnhI in regulating global and temporal HBV gene expression.
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PMID:Enhancer I predominance in hepatitis B virus gene expression. 1474 94

The nuclear hormone receptors hepatocyte nuclear factor 4 (HNF4) and retinoid X receptor alpha (RXRalpha) plus peroxisome proliferator-activated receptor alpha (PPARalpha) heterodimer support hepatitis B virus (HBV) pregenomic RNA synthesis and viral replication in nonhepatoma cells. Small heterodimer partner (SHP), an orphan nuclear hormone receptor lacking a DNA binding domain, inhibits nuclear hormone receptor-mediated viral transcription and replication. The inhibition of HBV replication by SHP is dependent on the presence of nuclear hormone receptors. HBV replication that is dependent on HNF4 is considerably more sensitive to SHP-mediated inhibition than RXRalpha/PPARalpha-directed viral biosynthesis. SHP inhibition of HBV biosynthesis in HepG2 cells suggests that multiple nuclear hormone receptors mediate viral replication in this human hepatoma cell line. These observations suggest that the physiological regulation of HBV biosynthesis by SHP in the liver will depend on both the level of SHP expression and the relative contribution of HNF4 and RXRalpha/PPARalpha, plus potentially additional nuclear hormone receptors, to HBV RNA synthesis and replication.
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PMID:Differential inhibition of nuclear hormone receptor-dependent hepatitis B virus replication by the small heterodimer partner. 1823 86

Hepatitis B virus (HBV) core promoter activity is positively and negatively regulated by nuclear receptors, a superfamily of ligand-activated transcription factors, via cis-acting sequences located in the viral genome. In this study, we investigated the role of farnesoid X receptor alpha (FXRalpha) in modulating transcription from the HBV core promoter. FXRalpha is a liver-enriched nuclear receptor activated by bile acids recognizing hormone response elements by forming heterodimers with retinoid X receptor alpha (RXRalpha). Electrophoretic mobility shift assays demonstrated that FXRalpha-RXRalpha heterodimers can bind two motifs on the HBV enhancer II and core promoter regions, presenting high homology to the consensus (AGGTCA) inverted repeat FXRalpha response elements. In transient transfection of the human hepatoma cell line Huh-7, bile acids enhanced the activity of a luciferase reporter containing the HBV enhancer II and core promoter sequences through FXRalpha. Moreover, using a greater-than-genome-length HBV construct, we showed that FXRalpha also increased synthesis of the viral pregenomic RNA and DNA replication intermediates. The data strongly suggest that FXRalpha is another member of the nuclear receptor superfamily implicated in the regulation of HBV core promoter activity and that bile acids could play an important role in the natural history of HBV infection.
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PMID:Transactivation of the hepatitis B virus core promoter by the nuclear receptor FXRalpha. 1876 87

Nuclear receptors have a unique role in governing hepatitis B virus (HBV) transcription and replication. Hepatocyte nuclear factor 4alpha (HNF4alpha) and retinoid X receptor alpha (RXRalpha) plus peroxisome proliferator-activated receptor alpha (PPARalpha) have been shown to support viral biosynthesis in nonhepatoma cells in the absence of additional liver-enriched transcription factors. However, the in vivo importance of these nuclear receptors in HBV biosynthesis has been investigated only to a limited extent. Fasting has been shown to activate gluconeogenesis, in part, by activating PPARgamma coactivator 1 alpha, which in turn leads to activation of HNF4alpha- and RXRalpha/PPARalpha-mediated transcription. As HBV pregenomic RNA synthesis is primarily believed to be regulated by HNF4alpha under normal physiological conditions, it was of interest to determine the effect of fasting on the levels of HBV RNA and DNA synthesis. Fasting was shown to rather modestly increase the levels of viral proteins, transcripts, and replication intermediates in the HBV transgenic mouse model of chronic viral infection, suggesting that caloric restriction may modulate viremia to some extent during natural infection.
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PMID:Limited effects of fasting on hepatitis B virus (HBV) biosynthesis in HBV transgenic mice. 1907 39


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