Hepatitis C virus core protein induces cell proliferation and activates ERK, JNK, and p38 MAP kinases together with the MAP kinase phosphatase MKP-1 in a HepG2 Tet-Off cell line.
Hepatitis C virus (HCV) core protein is a multifunctional protein interacting with cellular and viral proteins and promoters. A tetracycline-regulated system was used to generate a HepG2 Tet-Off cell line allowing regulated expression of a full-length (191 aa) and an N(c)-truncated core protein (160 aa). In this system HCV core protein expression activates extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 mitogen-activated protein (MAP) kinase, induces MAP kinase phosphatase MKP-1 expression, and increases cell proliferation. This was accompanied by an activation of c-Jun and ATF-2, but not Elk-1 and c-Fos. Furthermore, AP-1 activation was independent of c-Fos. Full-length and N(c)-truncated HCV core proteins exerted similar effects.
Erhardt
Andreas
A
Klinik für Gastroenterologie, Hepatologie, und Infektiologie, Heinrich-Heine-Universität Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany. erhardt@uni-duesseldorf.de
Hassan
Mohamed
M
Heintges
Tobias
T
Häussinger
Dieter
D
D002460:Cell Line / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects*; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology; D014758:Viral Core Proteins / Q000378:metabolism / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases
D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D013752:Tetracycline