Publications (2)16.45 Total impact
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Article: Hepatitis B virus X protein induces hepatic steatosis via transcriptional activation of SREBP1 and PPARgamma.
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ABSTRACT: Hepatic steatosis occurs frequently in patients with chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection. Recently, several studies suggested that steatosis plays an important role as a cofactor in other liver diseases such as hepatic fibrosis, hepatitis, and liver cancer. In contrast to HCV, however, the molecular mechanism by which HBV mediates hepatic steatosis has not been clearly studied. Here, we show the molecular mechanism by which hepatitis B virus X protein (HBx) induces hepatic steatosis. Lipid accumulation and the expression of various lipid metabolic genes were investigated in HBx-transfected Chang liver cells, HepG2-HBx stable cells, and HBx-transgenic mice. Overexpression of HBx induced hepatic lipid accumulation in HepG2-HBx stable cells and HBx-transgenic mice. It also up-regulated the messenger RNA and protein levels of sterol regulatory element binding protein 1, but not peroxisome proliferator-activated receptor alpha (PPARalpha). Moreover, we also determined that the expression of HBx increases PPARgamma gene expression as well as its transcriptional activity in hepatic cells, mediated by CCAAT enhancer binding protein alpha activation. Finally, we showed that HBx expression is able to up-regulate the gene expressions of various lipogenic and adipogenic enzymes in hepatic cells. We showed that the increased HBx expression causes lipid accumulation in hepatic cells mediated by sterol regulatory element binding protein 1 and PPARgamma, which could be a putative molecular mechanism mediating the pathophysiology of HBV infection.Gastroenterology 06/2007; 132(5):1955-67. · 11.68 Impact Factor -
Article: Activation and interaction of ATF2 with the coactivator ASC-2 are responsive for granulocytic differentiation by retinoic acid.
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ABSTRACT: Terminal differentiation of hematopoietic cells follows a precisely orchestrated program of transcriptional regulatory events at the promoters of both lineage-specific and ubiquitous genes. Here we show that the transcription factor ATF2 is associated with the induction of granulocytic differentiation, and the molecular interaction of ATF2 with a tissue-specific coactivator activating signal cointegator-2 (ASC-2) potentiates the differentiation procedure. All-trans retinoic acid (RA) induced the phosphorylation and expression of ATF2 in the early and middle phase of granulocyte differentiation, respectively. The activation of granulocyte-specific gene expression is increased with the concerted action of another basic regionleucine zipper factor, CCAAT/enhancer-binding protein (C/EBPalpha), and ASC-2, which function in a cooperative manner. The interaction between ATF2 and C/EBPalpha in RA-treated cells was enhanced by the ectopic expression of ASC-2. ATF2-mediated transactivation was also increased by co-transfection of ASC-2. This resulted from the direct protein interaction that the N-terminal transactivation domain of ATF2 interacts with the central region of ASC-2. Furthermore, the molecular interaction of ATF2 and ASC-2 was stimulated by RA treatment and inhibited by p38beta kinase inhibitor. Taking these results together, these results suggest that the differentiation-dependent expression and phosphorylation of ATF2 protein physically and functionally interacts with C/EBPalpha and coativator ASC-2 and synergizes to induce target gene transcription during granulocytic differentiation.Journal of Biological Chemistry 05/2004; 279(17):16996-7003. · 4.77 Impact Factor
