Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis B virus S transcripts contain a region, known as the posttranscriptional regulatory element (PRE), that activates their transport from the nucleus to the cytoplasm. J. Huang and T. J. Liang (Mol. Cell. Biol. 13:7476-7486, 1993) have shown that this element can partially substitute for the human immunodeficiency virus Rev-response element (RRE) in a reporter plasmid that is dependent on the RRE and Rev protein for expression and concluded that PRE exhibits Rev-RRE-like functions by inhibiting splicing. However, we have obtained additional data which indicate that the PRE functions in a novel manner that is not dependent on inhibition of splicing. Unlike Rev-RRE, the PRE functions independently of splice donor and acceptor sites and can activate cytoplasmic expression of an intronless (so-called prespliced) beta-globin transcript. Conversely, a heterologous intron can substitute for the PRE in increasing cytoplasmic expression of hepatitis B virus S transcripts. In addition, the host nuclear factor, YL2 (p32), which enhances Rev-RRE function has no effect on PRE-dependent gene expression. Since S transcripts are not normally known to be spliced and since RNA splicing and cytoplasmic transport are tightly linked processes in higher eucaryotic cells, we conclude that the PRE functions in cis to allow the export of nuclear transcripts that do not interact efficiently with the splicing pathway and hence are normally not exported well from the nucleus. Such elements are critical for the life cycle of viruses, such as hepatitis B virus, which undergo reverse transcription during replication.
Mol Cell Biol 1995 Jul
PMID:Role of the hepatitis B virus posttranscriptional regulatory element in export of intronless transcripts. 779 93

Transactivation by hepatitis B virus X protein (pX) is promiscuous, but it requires cellular activators. To study the mode of action of pX, we coexpressed pX with Gal4-derived activators in a cotransfection system. Twelve different activators bearing different types of activation domains were compared for their response to pX. Because pX indirectly increases the amount of the activators, tools were developed to compare samples with equivalent amount of activators. We demonstrate that pX preferentially coactivates potent activators, especially those with acidic activation domains. Weak activators with nonacidic activation domains are not potentiated by pX. Interestingly, Gal4E1a, which is not rich in acidic residues but interacts with similar molecular targets, also responds to pX. The response to pX correlated with the strength of the activation domain. Collectively, these data imply that pX is a coactivator, which offers a molecular basis for the pleiotropic effects of pX on transcription.
Mol Cell Biol 1995 Feb
PMID:The X protein of hepatitis B virus coactivates potent activation domains. 782 23

The relative roles of hepatitis B virus (HBV) and aflatoxin and their possible mechanism of interaction in the etiopathogenesis of hepatocellular carcinoma (HCC) are not understood. One hypothesis is that viral infection and associated liver injury alter expression of carcinogen-metabolizing enzymes. We tested this hypothesis in an HBV-transgenic mouse model in which a synergistic interaction occurs between aflatoxin B1 (AFB1) and HBV in the induction of HCC (Sell et al., Cancer Res 51:1278-1285, 1991). In this transgenic mouse lineage, overproduction of the HBV large envelope protein results in progressive liver cell injury, inflammation, and regenerative hyperplasia. Initially, two cytochrome P450s of importance in AFB1 metabolism in the mice were identified, namely Cyp2a-5 and Cyp3a, using specific antibodies and chemical inhibitors. The expression of these P450 isoenzymes and an alpha-class glutathione S-transferase (GST) isoenzyme, YaYa, were examined. Increased expression and altered distribution of Cyp2a-5 were demonstrated, by immunohistochemical analysis, to be associated with the development of liver injury in mice and to increase with age between 1 and 12 months. Cyp3a expression was also increased in HBV-transgenic mice, but the increase was not as clearly related to age. GST YaYa levels were the same in HBV-transgenic mice and their nontransgenic littermates of all ages. These results show that expression of specific cytochrome P450s is altered in association with overexpression of HBV large envelope protein and liver injury in this model. This may have general relevance to human HCC, the etiology of which is associated with a diverse range of liver-damaging agents.
Mol Carcinog 1994 Oct
PMID:Induction of specific cytochrome P450s involved in aflatoxin B1 metabolism in hepatitis B virus transgenic mice. 791 95

The large envelope glycoprotein (L protein) of Hepatitis B virus (HBV) contains the preS1 domain, which is responsible for retention of the protein in the endoplasmic reticulum. To identify sequences of the preS1 domain involved in this phenomenon we constructed vaccinia virus-HBV recombinants containing the gene for L protein in which the preS1 coding sequence had been partially deleted. The retention of L protein in the endoplasmic reticulum was found to be mediated by a sequence contained within a region of 35 amino acids of the preS1 C-terminus, and not exclusively by amino acid sequences of the N-terminus of the preS1 domain as proposed by Kuroki et al. (Mol. Cell. Biol. 9, 4459-4466, 1989). Our finding could be explained by a specifically VV promoter sequence leading to exclusive synthesis of L or deleted (delta)L proteins, respectively. The ability of the coexpressed HBV S protein to facilitate export of the delta L proteins was demonstrated by coinfection experiments.
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PMID:A carboxy-terminal portion of the preS1 domain of hepatitis B virus (HBV) occasioned retention in endoplasmic reticulum of HBV envelope proteins expressed by recombinant vaccinia viruses. 803 Feb 3

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in humans and in most cases a consequence of chronic infection of the liver by hepatotropic viruses (Hepatitis B Virus (HBV) and possibly Hepatitis C Virus (HCV)). Formation of HCC results from a stepwise process involving different preneoplastic lesions that reflect multiple genetic events, like protooncogene activation, tumor suppressor gene inactivation, and growth factor over- or reexpression. Recent investigations have gained new insights into how these factors are activated and may interact. In addition, improved knowledge of the molecular biology of HBV has led to better understanding of its pleiotropic effects on induction and progression in hepatocarcinogenesis.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Current pathogenetic and molecular concepts in viral liver carcinogenesis. 809 24

Biopsy specimens (n = 61) from patients with chronic active hepatitis B and progressive fibrosis (n = 61) were studied immunohistochemically to obtain information about the histogenesis of neoductules. All the biopsies contained clusters of oval-shaped cells often arranged in the form of neoductular aggregates. These expressed cytokeratins 7 and 19 which in the normal liver are found only in bile duct and ductular epithelium but not in hepatocytes. Using monoclonal and polyclonal antibodies both hepatocytes and these oval neoductular cells were found to express HBs- and HBc-antigen in 15% and 20% of the biopsies, respectively. Taking into consideration the strong hepatocytotropism of the hepatitis B virus, the expression of HBV-antigens in neoductular cells suggest their development from HBV-infected hepatocytes. Using proliferating cell nuclear antigen (PCNA) as a marker of cell proliferation positive staining was detected only in hepatocytes but not in neoductular cells. Taken together findings further support the concept of hepatoductular metaplasia in the histogenesis of so-called "proliferating" ductules. In general the data show that hepatitis B virus infection does not prevent hepatocytes from undergoing ductular metaplasia.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Expression of HBs- and HBc-antigen in neoductular epithelium in chronic active hepatitis B. A further support for hepato-ductular metaplasia. 809 73

A method for prediction of transmembrane segments from multiply aligned amino acid sequences is presented. For the calculations, two sets of propensity values were used: one for the middle, hydrophobic portion and one for the terminal regions of the transmembrane sequence spans. Average propensity values were calculated for each position along the alignment, with the contribution from each sequence weighted according to its dissimilarity relative to the other aligned sequences. Eight-residue segments were considered as potential cores of transmembrane segments and elongated if their middle propensity values were above a given threshold. End propensity values were also considered as stop signals. Only helices with length of 15 to 29 residues were allowed and corrections for strictly conserved charged residues were also made. The method is shown to be more successful than predictions based upon single sequences alone. In the test set of 28 families with 126 transmembrane segments, only five spans were not predicted or constituted false positives. The method is applied to sequence families for which data on transmembrane segments do not exist or are sparse or contradictory included voltage-gated potassium-channels, cytochrome c oxidases, NADH-ubiquinone oxidoreductase, beta-glucosides-specific phosphotransferase enzyme and major surface antigen of hepatitis B virus.
J Mol Biol 1994 Mar 25
PMID:Prediction of transmembrane segments in proteins utilising multiple sequence alignments. 812 32

We previously showed that hepatitis B surface antigen (HBsAg)-producing transgenic mice were more sensitive to hepatocarcinogens than their normal littermates were. We have now investigated the regulation of hepatitis B virus (HBV) gene expression in carcinogen-induced liver tumors of HBV-carrier transgenic mice and in three cell lines derived from tumor samples. Transcription of the S gene was repressed in 17 tumors even though they had normal levels of liver-specific mRNAs such as albumin and transferrin. Three hepatoma cell lines, derived from independent tumor samples, were analyzed for their capacity to express the S gene after transfection of cloned DNA. Although they no longer expressed the endogenous S gene, they were still able to express it from transfected viral DNA both transiently and stably. The loss of HBsAg expression in tumors and in the cell lines was accompanied by de novo methylation of the S region, which is a way to permanently repress gene expression. Our data confirm in an animal model previous observations of S-gene expression in human hepatocarcinoma and suggest a role for its downregulation in tumor progression.
Mol Carcinog 1994 Apr
PMID:Inhibition of hepatitis B virus surface antigen gene expression in carcinogen-induced liver tumors from transgenic mice. 814 51

Reexpression of the insulin-like growth factor type II (IGF-II) gene has recently been described in hepatocellular carcinoma (HCC). In this study, we used a nonisotopic in situ hybridization method to analyze the expression of IGF-II mRNA in a series of 28 HCCs arising on cirrhotic and noncirrhotic livers. An immunohistochemical method was used to detect IGF-II peptide. Hepatitis B virus (HBV) status and the histological differentiation degree were also evaluated. Increased expression of IGF-II mRNA was found in 4 of 28 HCCs, and 7 of 17 cirrhotic patients showed IGF-II mRNA in the cirrhotic nodules surrounding the HCC. A slightly higher rate of positivity for IGF-II mRNA was found in the HBV-negative patients than in HBV-positive ones. Positive immunostaining for the IGF-II peptide in the HCC and/or in surrounding cirrhotic nodules was found in 10 of 28 cases. The normal hepatocytes of the noncirrhotic patients were always negative for IGF-II peptide and mRNA. The similarities between our results and those from experimental models in woodchucks seem to support the concept that heterogeneous phenotypic groups could exist in human HCCs.
Diagn Mol Pathol 1994 Mar
PMID:Different in situ expression of insulin-like growth factor type II in hepatocellular carcinoma. An in situ hybridization and immunohistochemical study. 816 57

The hepatitis B virus 17 kDa x gene product expressed in bacteria transactivates a human U6 promoter three- to eightfold in an ATP-independent manner in HeLa cell NTP-depleted extracts containing preassembled transcription preinitiation complexes. However, if added prior to assembly, HBx squelches the promoter. Both the HBx dependent "squelching" of U6 transcription observed in transient transfection analysis, and the transactivation observed in vitro is dependent on the presence of an upstream octamer element. HBx is incorporated via protein-protein interactions into DNA complexes containing the activation domains of Oct-1, and into a stable U6 preinitiation complex. This is consistent with a role as a coactivator interacting with the basal transcription machinery. We propose that the HBx dependent transactivation and repression of U6 transcription occurs by changes in the transcription factor limiting initiation, and propose that HBx may have a dual role in the regulation of transcription in vivo.
Cell Mol Biol Res 1993
PMID:The 17 kDa HBx protein encoded by hepatitis B virus interacts with the activation domains of Oct-1, and functions as a coactivator in the activation and repression of a human U6 promoter. 817 91


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