C M Chen

Chang Gung Memorial Hospital, Taipei, Taipei, Taiwan

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Publications (6)21.94 Total impact

  • Digestive Diseases and Sciences 04/2001; 46(3):486-8. · 2.55 Impact Factor
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    ABSTRACT: The nucleocapsid core protein of hepatitis C virus (HCV) has been shown to trans-act on several viral or cellular promoters. To get insight into the trans-action mechanism of HCV core protein, a yeast two-hybrid cloning system was used for identification of core protein-interacting cellular protein. One such cDNA clone encoding the DEAD box family of putative RNA helicase was obtained. This cellular putative RNA helicase, designated CAP-Rf, exhibits more than 95% amino acid sequence identity to other known RNA helicases including human DBX and DBY, mouse mDEAD3, and PL10, a family of proteins generally involved in translation, splicing, development, or cell growth. In vitro binding or in vivo coimmunoprecipitation studies demonstrated the direct interaction of the full-length/matured form and C-terminally truncated variants of HCV core protein with this targeted protein. Additionally, the protein's interaction domains were delineated at the N-terminal 40-amino-acid segment of the HCV core protein and the C-terminal tail of CAP-Rf, which encompassed its RNA-binding and ATP hydrolysis domains. Immunoblotting or indirect immunofluorescence analysis revealed that the endogenous CAP-Rf was mainly localized in the nucleus and to a lesser extent in the cytoplasm, and when fused with FLAG tag, it colocalized with the HCV core protein either in the cytoplasm or in the nucleus. Similar to other RNA helicases, this cellular RNA helicase has nucleoside triphosphatase-deoxynucleoside triphosphatase activity, but this activity is inhibited by various forms of homopolynucleotides and enhanced by the HCV core protein. Moreover, transient expression of HCV core protein in human hepatoma HuH-7 cells significantly potentiated the trans-activation effect of FLAG-tagged CAP-Rf or untagged CAP-Rf on the luciferase reporter plasmid activity. All together, our results indicate that CAP-Rf is involved in regulation of gene expression and that HCV core protein promotes the trans-activation ability of CAP-Rf, likely via the complex formation and the modulation of the ATPase-dATPase activity of CAP-Rf. These findings provide evidence that HCV may have evolved a distinct mechanism in alteration of host cellular gene expression regulation via the interaction of its nucleocapsid core protein and cellular putative RNA helicase known to participate in all aspects of cellular processes involving RNA metabolism. This feature of core protein may impart pleiotropic effects on host cells, which may partially account for its role in HCV pathogenesis.
    Journal of Virology 05/1999; 73(4):2841-53. · 4.65 Impact Factor
  • Gastrointestinal Endoscopy 03/1999; 49(2):257-9. DOI:10.1016/S0016-5107(99)70499-2 · 4.90 Impact Factor
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    C M Chen, L R You, L H Hwang, Y H Lee
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    ABSTRACT: Previous studies suggest that the core protein of hepatitis C virus (HCV) has a pleiotropic function in the replication cycle of the virus. To understand the role of this protein in HCV pathogenesis, we used a yeast two-hybrid protein interaction cloning system to search for cellular proteins physically interacting with the HCV core protein. One such cellular gene was isolated and characterized as the gene encoding the lymphotoxin-beta receptor (LT-betaR). In vitro binding analysis demonstrated that the HCV core protein binds to the C-terminal 98 amino acids within the intracellular domain of the LT-betaR that is involved in signal transduction, although the binding affinity of the full-length HCV core protein was weaker than that of its C-terminally truncated form. Our results also indicated that the N-terminal 40-amino-acid segment of the HCV core protein was sufficient for interaction with LT-betaR and that the core protein could form complexes with the oligomeric form of the intracellular domain of LT-betaR, which is a prerequisite for downstream signaling of this receptor. Similar to other members of the tumor necrosis factor (TNF) receptor superfamily, LT-betaR is involved in the cytotoxic effect of the signaling pathway, and thus we have elucidated the biological consequence of interaction between the HCV core protein and LT-betaR. Our results indicated that in the presence of the synergizing agent gamma interferon, the HCV core protein enhances the cytotoxic effects of recombinant forms of LT-betaR ligand in HeLa cells but not in hepatoma cells. Furthermore, this enhancement of the cytolytic activity was cytokine specific, since in the presence of cycloheximide, the expression of the HCV core protein did not elicit an increase in the cytolytic activity of TNF in both HeLa and hepatoma cells. In summary, the HCV core protein can associate with LT-betaR, and this protein-protein interaction has a modulatory effect on the signaling pathway of LT-betaR in certain cell types. Given the known roles of LT-betaR/LT-alpha1,beta2 receptor-ligand interactions in the normal development of peripheral lymphoid organs and in triggering cytolytic activity and NF-kappaB activation in certain cell types, our finding implies that the HCV core protein may aggravate these biological functions of LT-betaR, resulting in pathogenesis in HCV-infected cells.
    Journal of Virology 01/1998; 71(12):9417-26. · 4.65 Impact Factor
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    ABSTRACT: A wide variety of neoplastic lesions may involve the ampulla of Vater, but squamous cell carcinoma has not been reported. Here we report a case of squamous cell carcinoma of papilla Vater. A 72-year-old Chinese female was manifested by obstructive jaundice and biliary tract infection. Duodenoscopic study revealed a polypoid mass with deep and broad ulcer on the ampulla of Vater. Histological examination revealed a metastatic squamous cell carcinoma. The gynecologist had examined the patient carefully and revealed a negative tumor survey. Other sources were also intensively studied but which revealed nothing. The patient developed biliary tree infection after endoscopic retrograde cholangiopancreatic study so that percutaneous transhepatic cholangiography & drainage was performed. Pseudomonas aeruginosa and Enterococcus were cultured from the drainaged bile. Radiotherapy was used and the bleeding was halted temporarily but the patient later expired due to persistent bleeding.
  • Endoscopy 03/1996; 28(2):262. DOI:10.1055/s-2007-1005442 · 5.20 Impact Factor

Publication Stats

205 Citations
21.94 Total Impact Points


  • 1996–2001
    • Chang Gung Memorial Hospital
      • • Department of Pathology
      • • Division of Hepato-Gastroenterology
      • • Division of Gastroenterology and Hepatology
      Taipei, Taipei, Taiwan
  • 1998
    • National Yang Ming University
      • Department of Biochemistry
      Taipei, Taipei, Taiwan