Asabe S I, Tanji Y, Satoh S, Kaneko T, Kimura K, Shimotohno K
Virology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
J Virol. 1997 Jan;71(1):790-6. doi: 10.1128/JVI.71.1.790-796.1997.
We previously showed that two proteins, a 56-kDa protein (p56) and a 58-kDa protein (p58), are produced from the hepatitis C virus (HCV) nonstructural 5A region (NS5A) and that the production of p58 is enhanced by the presence of NS4A (T. Kaneko, Y. Tanji, S. Satoh, M. Hijikata, S. Asabe, K. Kimura, and K. Shimotohno, Biochem. Biophys. Res. Commun. 205:320-326, 1994). Both proteins have phosphorylated serine residues, some of which are located in the C-terminal region. In p58, phosphorylation of serine residues in the central region of HCV NS5A is important for production of p58 in an NS4A-dependent manner. To clarify the mechanism of NS5A phosphorylation, in particular phosphorylation in the central region, phosphorylation of deleted and mutated forms of NS5A was analyzed using a transient protein production system in cultured cells in the presence or absence of NS4A. Association of the NS5A region from amino acids 2135 to 2139 with NS4A was important for NS4A-dependent phosphorylation of NS5A.
我们之前的研究表明，丙型肝炎病毒（HCV）非结构5A区（NS5A）可产生两种蛋白质，一种是56 kDa的蛋白质（p56），另一种是58 kDa的蛋白质（p58），并且NS4A的存在会增强p58的产生（T. Kaneko、Y. Tanji、S. Satoh、M. Hijikata、S. Asabe、K. Kimura和K. Shimotohno，《生物化学与生物物理研究通讯》205:320 - 326，1994年）。这两种蛋白质都有磷酸化的丝氨酸残基，其中一些位于C末端区域。在p58中，HCV NS5A中央区域丝氨酸残基的磷酸化对于以NS4A依赖的方式产生p58很重要。为了阐明NS5A磷酸化的机制，特别是中央区域的磷酸化，我们在有或没有NS4A存在的情况下，利用培养细胞中的瞬时蛋白质产生系统分析了NS5A缺失和突变形式的磷酸化情况。NS5A氨基酸2135至2139区域与NS4A的结合对于NS5A的NS4A依赖型磷酸化很重要。
