| Summary: | 碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 93 === HBV (hepatitis B virus) infection is a major cause of hepatitis, cirrhosis and hepatocellular carcinoma (HCC), which is an important global health issue. Expression and distribution of HBV core protein are tightly correlated with the progression of liver disease in patients with chronic HBV infection, suggesting that core protein is involved in the pathogenesis of chronic HBV infection. To identify the role of core protein in the HBV pathogenesis, our lab has previously used the C-terminal 67-amino acid region of core protein as a bait to screen a liver cDNA library by yeast two hybrid system. A protein tyrosine phosphatase PTPH1 consisting of a N-terminal FERM domain, a middle PDZ domain, and a C-terminal phosphatase domain was found to interact with the C-terminal region of core protein. The minimal interaction between the core protein and PTPH1 was through the PDZ domain of PTPH1 and the C-terminal last four amino acid residues, ESQC, of core protein. Besides, the FERM domain of PTPH1 is also essential for the interaction. Furthermore, the phosphatase activity and phosphorylation of Serine359 and Serine835 of PTPH1 were not required for the PTPH1-core interaction. When PTPH1 and core protein were co-expressed in HuH-7 cells, PTPH1 changes the localization of core protein, from the nucleus to the cytoplasm. The cytoplasmic localization of core protein depends on the interaction with PTPH1. On the other hand, PTPH1 protein over-expression strongly reduced the levels of HBV transcripts and the in turn viral particle production. However, the PTPH1-mediated suppression effect did not require the PTPH1-core interaction nor the existence of core protein. The PTPH1-mediated suppressive effect required the phosphatase activity and FERM domain but not the localization of PTPH1 neither the phosphorylation of Serine359 and Serine835 of PTPH1. Whether PTPH1 mediated the suppressive effect is through its substrate VCP and/or NF-κB needs more characterization.
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