| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
To clarifiy the molecular mechanism of hepatitis and hepatocellular carcinoma caused by hepatitis C virus (HCV), we analysed the mechanism of anti-apoptotic effect by HCV core protein in this research project. The achievements are listed bellow.
1. Results obtained from analysis of the molecular mechanism for activation of cellular transcription factor NF-κB by HCV core protein which is thought be one of important machinary for the anti-apoptotic effect of the core portein. are shown as follows ;
(1) From th edeletion analysis and and the observation of subcellular localization, it was revealed that the localization of the HCV core protein in the cytoplasm, especially on the endoplasmic reticulum membranes, is important for the NF-κB activation. .
(2) We found that the minimum region required for NF-κB activation just like as authentic core protein is located at the amino-terminal portion, from aa20 to aa80, of the HCV core protein.
(3) We are trying to characterize several cDNA clones obtained by yeast two hybrid system using the region from aa 20 to aa 80 of the core as a bait.
(4) We showed that the core protein enhanced the NF-κB activity induced by the overexpression of IKKβ, which is a kinase for the phosphorylation of IκB, without augmentation of IKKβ activity, suggesting that the core protein affects the point downstream of IKKβin thee NF-κB activation pathway to enhance the NF-κB activity.
2. We analysed the molecular mechanism of activation of MAP kinase pathway by the core protein and obtained the results showing that the coree protein augments the activity of transcription factor Elk1 by the unknow mechaism which is different from the well-known kination reaction.
Since the activation of the tramscription factors by the HCV core protein seems to be closely related with the suppression of apoptosis, persistent infection of HCV, and hepatocellular carcinogenesis, further analysis of molecular mechanisms is now underway.
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