Phosphorylation of human La protein at Ser366 by CK2 contributes to HBV replication and expression in vitro
Human La protein (hLa) is a multifunctional RNA-binding protein involved in the regulation of hepatitis B virus (HBV) expression.Casein kinase Ⅱ (CK2),a protein kinase,is known to activate hLa by phosphorylating Ser366.Tetrabromobenzimidazole (TBBz) has been shown to be a specific inhibitor of CK2 activity,which suggests that TBBz may be useful for reducing HBV gene expression.The aim of our study was to determine if inhibition of CK2 by TBBz and decreased phosphorylation of hLa Ser (pLa) would reduce HBV gene expression.pLa and total La expression levels were evaluated by immunohistochemistry in human liver tissues with or without HBV infection.HepG2.2.15 cells (an HBV-expressing cell line) were treated with TBBz,and cell viability and pLa levels were evaluated.Knockdown of hLa and CK2 levels by specific siRNA and mutant hLa Ala were utilized to establish the roles of pLa and CK2 in HBV gene expression.HBV DNA replication and HBsAg and HBeAg levels were analyzed in HepG2.2.15 cell supernatants by standard methods.pLa was significantly overexpressed in HBV-infected human liver samples.TBBz decreased the phosphorylation of hLa,which coincided with decreased HBV expression.Mutant hLa Ala had reduced viral expression compared with hLa Sertreatment in hLa siRNA knockdown cells.Knockdown of CK2 also decreased the HBV parameters.hLa plays a key role in the regulation of HBV gene expression in a CK2-dependent mechanism via phosphorylation of hLa at Ser.
human La protein casein kinase Ⅱ hepatitis B virus phosphorylation
TANG Jing HEISE Tilman LIU Gao-Lin
Department of Pharmacy,Shanghai First People’s Hospital,School of Medicine,Shanghai JiaoTong Univers Department of Biochemistry & Molecular Biology,Medical University of South Carolina,Charleston,SC,US
国内会议
南宁
英文
1-15
2013-11-01（万方平台首次上网日期，不代表论文的发表时间）