title: Activation of c-Jun NH2-terminal kinase (JNK) signaling pathway is essential for the stimulation of hepatitis C virus (HCV) non-structural protein 3 (NS3)-mediated cell growth.
abstract: Hepatitis C virus (HCV) non-structural protein 3 (NS3) has been shown to affect cellular functions and is thought to contribute to the development of HCV-related hepatocarcinogenesis. In this study, we delineated part of the mechanisms whereby NS3 protein stimulates cell growth in liver (HepG2) and non-liver (HeLa) cells. The expression of NS3 protein enhanced cell growth, c-jun NH(2)-terminal kinase (JNK) activation, DNA binding activities of the transcription factors AP-1 and ATF-2, and c-jun expression, but not the activation of extracellular signal-regulated kinase (ERK) or p38(MAPK). Whereas co-expression of NS3 with its cofactor NS4A inhibited NS3-mediated cell growth without to influence NS3-mediated JNK activation, or to affect the basal activities of ERK or p38(MAPK). Pre-treatment of NS3 protein-expressing cells with JNK inhibitor, SP600125, abolished activation of AP-1 and ATF-2 and inhibited c-jun expression and induced cell growth, suggesting that JNK activation is essential for the stimulation of NS3-mediated cell growth.
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Duesseldorf, Mooren Str.5, 40225 Duesseldorf, Germany.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hassan
authors.forename: Hanan
authors.initials: H
authors.lastname: Ghozlan
authors.forename: Ola
authors.initials: O
authors.lastname: Abdel-Kader
mesh_terms: D051698:Activating Transcription Factor 2; D000873:Anthracenes / Q000494:pharmacology; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects; D006367:HeLa Cells; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D013752:Tetracycline / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D051698:Activating Transcription Factor 2; D000873:Anthracenes; D017362:Cyclic AMP Response Element-Binding Protein; D004279:DNA, Viral; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D013752:Tetracycline; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D017361:Viral Nonstructural Proteins; D048051:p38 Mitogen-Activated Protein Kinases; C497105:ATF2 protein, human; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; C432165:pyrazolanthrone