Activation of the IGF-II gene by HBV-X protein requires PKC and p44/p42 map kinase signalings.
We have recently shown that HBx protein, one of the causative agents of hepatocellular carcinomas, regulates Sp1 mediated transcription of insulin-like growth factor II promoter 4 (Lee et al. (1998) Oncogene 16, 2367-2380). Here we show that PKC and p44/p42MAPK signalings are required for the HBx-induced Sp1-mediated IGF-II P4 transcriptional activity since (i) PKC activation by PMA or PKC expression vector increases Sp1 phosphorylation and P4 activity in HBx-transfected HepG2 cells; (ii) PKC inhibition by PKC inhibitor Gö6976 reduces Sp1 phosphorylation, P4 activity, and IGF-II mRNA in HBx-transfected HepG2 cells; and (iii) the inhibition of MEK activation by U0126 reduces Sp1 phosphorylation, P4 activity and IGF-II mRNA in HBx-transfected HepG2 cells. These results demonstrate that PKC and p44/p42 MAPK cascades are the essential signaling pathways in Sp1-mediated IGF-II gene activation by HBx.
Kang-Park
S
S
Liver Cell Signal Transduction Laboratory, Korea Research Institute of Bioscience and Biotechnology, Taejon, 305-606, Korea.
Lee
J H
JH
Shin
J H
JH
Lee
Y I
YI
D002227:Carbazoles / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006511:Hepatitis B Antigens / Q000235:genetics / Q000633:toxicity; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000633:toxicity*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins
D002227:Carbazoles; D004791:Enzyme Inhibitors; D006511:Hepatitis B Antigens; D007211:Indoles; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C081021:Go 6976; D007335:Insulin-Like Growth Factor II; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases