Association of hepatitis B virus polymerase with promyelocytic leukemia nuclear bodies mediated by the S100 family protein p11
Association of hepatitis B virus polymerase with promyelocytic leukemia nuclear bodies mediated by the S100 family protein p11
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DOI：
10.1016/s0006-291x(03)00881-7
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发表时间：
2003-06-13
影响因子：
3.1
通讯作者：
Han, YS
中科院分区：
文献类型：
--
作者：
Choi, J;Chang, JS;Han, YS
B型肝炎病毒（HBV）聚合酶（Pol）与细胞伴侣蛋白相互作用，从而执行病毒复制所必需的多种功能。应用酵母双杂交分析来鉴定HBV Pol功能所需的其他细胞靶标。HBV Pol与S100 A10（p11）相互作用，S100 A10（p11）是一种先前显示与膜联蛋白II结合的Ca 2+调节蛋白。通过体外或转染细胞中合成的两种蛋白质的免疫共沉淀以及p11对HBV Pol DNA聚合酶活性的抑制，证实了HBV Pol和p11之间的相互作用。转染的人细胞系的免疫荧光分析显示，虽然大多数HBV Pol和p11被限制在细胞质中，但每种蛋白质的一小部分共定位为核斑点;在p11不存在的情况下，在细胞核中未检测到HBV Pol。HBV Pol-p11核斑点与含有早幼粒细胞白血病蛋白PML的核体相一致。此外，HBV Pol-p11与PML的相关性通过细胞暴露于EGTA而增加，并被缬氨霉素抑制。这些结果表明p11 n调节HBV Pol功能的作用，并暗示PML核体和细胞内Ca 2+在病毒复制中的作用。(C)2003 Elsevier Science（美国）。All rights reserved.
Hepatitis B virus (HBV) polymerase (Pol) interacts with cellular chaperone proteins and thereby performs multiple functions necessary for viral replication. Yeast two-hybrid analysis was applied to identify additional cellular targets required for HBV Pol function. HBV Pol interacted with S100A10 (p11), a Ca2+-modulated protein previously shown to bind to annexin II. The interaction between HBV Pol and p11 was confirmed by co-immunoprecipitation of the two proteins synthesized either in vitro or in transfected cells and by inhibition of the DNA polymerase activity of HBV Pol by p11. Immunofluorescence analysis of transfected human cell lines revealed that, although most HBV Pol and p11 was restricted to the cytoplasm, a small proportion of each protein colocalized as nuclear speckles; HBV Pol was not detected in the nucleus in the absence of p11. The HBV Pol-p11 nuclear speckles coincided with nuclear bodies containing the promyelocytic leukemia protein PML. Furthermore, the association of HBV Pol-p11 with PML was increased by exposure of cells to EGTA and inhibited by valinomycin. These results suggest a role for p11 n modulation of HBV Pol function and implicate PML nuclear bodies and intracellular Ca2+ in viral replication. (C) 2003 Elsevier Science (USA). All rights reserved.