乙型肝炎病毒X蛋白对胰岛素样生长因子-II基因的激活需要蛋白激酶C和p44/p42丝裂原活化蛋白激酶信号传导。
Activation of the IGF-II gene by HBV-X protein requires PKC and p44/p42 map kinase signalings.
作者信息
Kang-Park S, Lee J H, Shin J H, Lee Y I
机构信息
Liver Cell Signal Transduction Laboratory, Korea Research Institute of Bioscience and Biotechnology, Taejon, 305-606, Korea.
出版信息
Biochem Biophys Res Commun. 2001 May 4;283(2):303-7. doi: 10.1006/bbrc.2001.4767.
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.
我们最近发现，乙型肝炎病毒X蛋白（HBx蛋白）作为肝细胞癌的致病因子之一，可调节Sp1介导的胰岛素样生长因子II启动子4的转录（Lee等人，《癌基因》，1998年，第16卷，2367 - 2380页）。在此我们表明，PKC和p44/p42 MAPK信号传导对于HBx诱导的Sp1介导的IGF-II P4转录活性是必需的，因为：（i）佛波酯（PMA）激活PKC或PKC表达载体可增加HBx转染的HepG2细胞中Sp1的磷酸化及P4活性；（ii）PKC抑制剂Gö6976抑制PKC可降低HBx转染的HepG2细胞中Sp1的磷酸化、P4活性及IGF-II mRNA水平；（iii）U0126抑制MEK激活可降低HBx转染的HepG2细胞中Sp1的磷酸化、P4活性及IGF-II mRNA水平。这些结果表明，PKC和p44/p42 MAPK级联反应是HBx介导Sp1激活IGF-II基因的重要信号通路。
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