Calcium signaling by HBx protein in hepatitis B virus DNA replication

被引:312
作者
Bouchard, MJ [1 ]
Wang, LH [1 ]
Schneider, RJ [1 ]
机构
[1] NYU, Dept Microbiol, New York, NY 10016 USA
关键词
D O I
10.1126/science.294.5550.2376
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hepatitis B virus (HBV) infects more than 300 million people and is a leading cause of liver cancer and disease. The HBV HBx: protein is essential for infection; HBx activation of Src is important for HBV DNA replication. In our study, HBx activated cytosolic calcium-dependent proline-rich tyrosine kinase-2 (Pyk2), a Src kinase activator. HBx activation of HBV DNA replication was blocked by inhibiting Pyk2 or calcium signaling mediated by mitochondrial calcium channels, which suggests that HBx targets mitochondrial calcium regulation. Reagents that increased cytosolic calcium substituted for HBx protein in HBV DNA replication. Thus, alteration of cytosolic calcium was a fundamental requirement for HBV replication and was mediated by HBx protein.
引用
收藏
页码:2376 / 2378
页数:3
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