Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis B virus X protein (HBx) is a promiscuous transcriptional transactivator of many viral and cellular promoters. HBx plays an important role in hepatitis B virus pathogenesis related with liver diseases including hepatocellular carcinoma (HCC). HBx is also involved in the signal transduction and the apoptosis of HBV-infected cells. However, the exact mechanism of apoptosis by HBx is still controversial. To demonstrate the mechanism of apoptosis by HBx, we induced the apoptosis of HBx-expressing liver cells, HepG2-X, by UV irradiation. We found that HepG2-X was much more sensitive to the UV-induced apoptosis than normal liver cells by analyzing the DNA fragmentation and the cell viability. Very interestingly, when the Fas-associated death domain (FADD)-dominant negative mutant protein was present in HepG2-X, the sensitized apoptotic response of HepG2-X to UV was completely abolished suggesting that there is a close relationship between HBx and Fas pathway in apoptosis. Therefore we examined the transactivation of Fas receptor (Fas) promoter and Fas ligand (FasL) promoter by HBx. We found that HBx strongly transcriptionally transactivated FasL promoter, but not Fas promoter. In addition, it also turned out that the mRNA levels of FasL are higher than those of Fas in HepG2-X. Taken together, HBx sensitizes the apoptosis of UV-irradiated liver cells by transcriptional transactivation of FasL gene.
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PMID:Hepatitis B virus X protein sensitizes UV-induced apoptosis by transcriptional transactivation of Fas ligand gene expression. 1620 85

Chronic hepatitis B is the most common cause of hepatocellular carcinoma (HCC) in Asia. Integration of hepatitis B virus (HBV) genome is likely an early event of carcinogenesis. The integrated HBV genome may activate neighboring cellular genes directly to offer a selective growth advantage to the liver cells. Production of hepatitis B X protein can act as a transactivator on various cellular genes for tumor development. Hepatic inflammation and cirrhosis also favors the process of carcinogenesis. Various viral factors associated with hepatocellular carcinoma development include HBV genotype, basal core promoter mutations, and high viral load. Polymorphisms at the androgen receptor-regulating genes and cytokine genes are possible host factors associated with HCC. This review article summarizes the pathogenesis of HBV-related carcinogenesis and the viral and host factors that may increase the risk of HCC development.
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PMID:Hepatocellular carcinoma and hepatitis B virus. 1667 93

The HBx (X protein of hepatitis B virus) is a promiscuous transactivator implicated to play a key role in hepatocellular carcinoma. However, HBx-regulated molecular events leading to deregulation of cell cycle or establishment of a permissive environment for hepatocarcinogenesis are not fully understood. Our cell culture-based studies suggested that HBx had a profound effect on cell cycle progression even in the absence of serum. HBx presence led to an early and sustained level of cyclin-cdk2 complex during the cell cycle combined with increased protein kinase activity of cdk2 heralding an early proliferative signal. The increased cdk2 activity also led to an early proteasomal degradation of p27(Kip1) that could be reversed by HBx-specific RNA interference and blocked by a chemical inhibitor of cdk2 or the T187A mutant of p27. Further, our co-immunoprecipitation and in vitro binding studies with recombinant proteins suggested a direct interaction between HBx and the cyclin E/A-cdk2 complex. Interference with different signalling cascades known to be activated by HBx suggested a constitutive requirement of Src kinases for the association of HBx with these complexes. Notably, the HBx mutant that did not interact with cyclin E/A failed to destabilize p27(Kip1) or deregulate the cell cycle. Thus HBx appears to deregulate the cell cycle by interacting with the key cell cycle regulators independent of its well-established role in transactivation.
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PMID:HBx-dependent cell cycle deregulation involves interaction with cyclin E/A-cdk2 complex and destabilization of p27Kip1. 1693 21

The progression of chronic hepatitis B (CHB) is related to fibrosis and to the emergence of intrahepatic anomalous vascular structures. Hepatitis B virus (HBV) X protein transactivator (HBx) may play a significant role in both processes. To analyze how HBV induces vascular growth and remodeling in vivo, we assessed the expression of angiopoietin-2 (Ang2) in liver biopsies from CHB patients by reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry because of the relevant role of Ang2 in vascular development, remodeling, and tumor promotion. In addition, we analyzed the influence of HBx in the expression of Ang2 in HBx-expressing hepatocyte cell lines and in hepatic stellate cells stimulated with conditional medium from HBx-hepatocytes. Ang2 expression was clearly up-regulated at both mRNA and protein levels in the liver of CHB patients, showing an intense staining of inflammatory infiltrates and vascular structures at inflamed portal areas. HBx-expressing hepatocytes and stimulated stellate cells showed a significant induction of Ang2 expression. PI3K inhibitor and antioxidants repressed the 64-kd Ang2 form but further enhanced the inflammation-related 50-kd molecular species. Therefore, HBx could account for the induction of Ang2 observed in CHB, especially the 50-kd form, contributing to pathological angiogenesis and hepatocellular carcinoma progression.
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PMID:Hepatitis B virus promotes angiopoietin-2 expression in liver tissue: role of HBV x protein. 1700 80

There is an increasing appreciation of the potential of cell-penetrating peptides (CPPs) as vectors to deliver peptides, proteins, and DNA into cells. However, the absolute and relative efficacy of various CPPs for applications targeting stem cells and primary cells is unclear. In this study, we have developed a two-step loading method and a flow cytometric assay to systematically compare the cellular uptake of five CPPs into embryonic stem cells, neurospheres (NSs), primary bone marrow hematopoietic progenitor (Sca-1(+)Lin(-)) cells, and hematopoietic cell lines (TF-1, K562, and FDCP Mix). The series of CPPs tested included three arginine-rich peptides; one was derived from HIV transactivator of transcription (TAT), one was derived from Antennapedia (Antp), and the third was a synthetic peptide known as protein transduction domain 4 (PTD4). Two hydrophobic peptides were also tested; one was derived from Kaposi fibroblast growth factor (K-FGF), and one was derived from PreS2 surface antigen of hepatitis B virus (PreS2-TLM). Our results indicate, for the first time, that arginine-rich CPPs can internalize into primary NSs and bone marrow Sca-1(+)Lin(-) cells. In addition, in all cell types examined, the uptake of arginine-rich CPPs is significantly greater than that of hydrophobic peptides.
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PMID:Flow cytometric screening of cell-penetrating peptides for their uptake into embryonic and adult stem cells. 1737 77

Hepatitis B virus X protein (HBx) is essential for hepatitis B virus infection and exerts a pleiotropic effect on various cellular machineries. HBx has been also demonstrated as an indirect transcriptional transactivator of various different viral and cellular promoters. In addition, HBx is involved in the development of various liver diseases including hepatocellular carcinoma. However the mechanism of HBx in hepatocellular carcinogenesis remains largely unknown. In this study, to identify possible new cellular proteins interacting with HBx, we carried out yeast two-hybrid assay. We obtained several possible cellular partners including VBP1, a binding factor for VHL tumor suppressor protein. The direct physical interaction between HBx and VBP1 in vitro and in vivo was confirmed by immunoprecipitation assay. In addition, we found that VBP1 facilitates HBx-induced NFkappaB activation and cell proliferation. These results implicate the important role of HBx in the development of hepatocellular carcinoma through its interaction with VBP1.
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PMID:Hepatitis B virus X protein enhances NFkappaB activity through cooperating with VBP1. 1831 53

Primary hepatocellular carcinoma (HCC) is one of the most common cancers occurring in human, and there is strong epidemiological evidence suggesting that persistent hepatitis B virus (HBV) infection is the most important risk factor for its development.HBx gene was found to be a transactivator recently. Its continuous expression in hepatocytes may transactivate cellular genes which can play a certain role in development of HCC. TheHBx gene fragment was used to construct a recombinant eukaryotic expression vector pCEP4 and introduced into HepG2 cells. The effect ofHBx gene on HCC cells growth and its molecular mechanism in HCC cells regulation were investigated.
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PMID:The role of hepatitis B virus x gene in development of primary hepatocellular carcinoma. 1872 85

Hepatitis B virus (HBV), a major causative agent of hepatocelluar carcinoma (HCC), encodes an oncogenic X-protein (HBx) which has been known as a transcriptional transactivator on multiple viral and celluar promoters. In the report, we verified that HBx transcriptionally repress insulin-like growth factor binding protein-3 (IGFBP-3) by promoting HBx/histone deacetylase 1 (HDAC1) complex formation. HBx recruited HDAC1 forms complex with Sp1 in a p53-independent manner) and deacetylates Sp1 which resulted in the diminished binding of Sp1 on targeted DNA during transcriptional repression. Deacetylation of Sp1 by HBx recruited HDAC1 likely to be a part of the mechanism that controls HBx induced IGFBP-3 repression and the modification of chromatin structure.
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PMID:Hepatitis B virus-X protein recruits histone deacetylase 1 to repress insulin-like growth factor binding protein 3 transcription. 1894 52

Human enteric adenoviruses (HAdVs; serotypes 40 and 41) are important waterborne and food-borne pathogens. However, HAdVs are fastidious, are difficult to cultivate, and do not produce a clear cytopathic effect during cell culture within a reasonable time. Thus, we examined whether the viral transactivator proteins cytomegalovirus (CMV) IE1 and hepatitis B virus (HBV) X promoted the multiplication of HAdVs. Additionally, we constructed a new 293 cell line expressing CMV IE1 protein for cultivation assays. We analyzed the nucleic acid sequences of the promoter regions of both E1A and hexon genes, which are considered to be the most important regions for HAdV replication. Expression of either HBV X or CMV IE1 protein significantly increased the promoter activities of E1A and hexon genes of HAdVs by as much as 14-fold during cell cultivation. The promotion of HAdV expression was confirmed by increased levels of both adenoviral DNA and mRNA expression. Finally, the newly developed 293 cell line expressing CMV IE1 protein showed an increase in viral DNA ranging from 574% to 619% compared with the conventional 293 cell line. These results suggest that the newly constructed cell line could be useful for efficient cultivation and research of fastidious HAdVs.
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PMID:Enhancement of enteric adenovirus cultivation by viral transactivator proteins. 2013 15

Hepatitis B viral X protein (HBx) is a multifunctional transactivator and implicated in hepatitis B virus (HBV) replication and hepatocarcinogenesis. HBx can be ubiquitinated and degraded through ubiquitin-proteasome pathway. However, the E3 ubiquitin ligase regulating HBx ubiquitin-dependent degradation is still unknown. In this study, we identified Siah-1 as a novel E3 ubiquitin ligase for HBx, which interacted with HBx and facilitated HBx poly-ubiquitylation and proteasomal degradation. Co-expression of Siah-1 attenuated the transcriptional transactivation of HBx on glucocorticoid response element (GRE), heat shock response element (HSE) and cAMP response element (CRE) signal pathways. Moreover, Siah-1 participated in p53-mediated HBx degradation. Therefore, Siah-1 may play important roles in ubiquitin-dependent degradation of HBx and may be involved in suppressing the progression of hepatocellular carcinoma (HCC).
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PMID:E3 ubiquitin ligase Siah-1 facilitates poly-ubiquitylation and proteasomal degradation of the hepatitis B viral X protein. 2187 28


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