PHOSPHORYLATION AND NUCLEAR-LOCALIZATION OF THE HEPATITIS-B VIRUS CORE PROTEIN - SIGNIFICANCE OF SERINE IN THE 3 REPEATED SPRRR MOTIFS
PHOSPHORYLATION AND NUCLEAR-LOCALIZATION OF THE HEPATITIS-B VIRUS CORE PROTEIN - SIGNIFICANCE OF SERINE IN THE 3 REPEATED SPRRR MOTIFS
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DOI：
10.1128/jvi.69.2.1025-1029.1995
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发表时间：
1995-02-01
影响因子：
5.4
通讯作者：
OU, JH
中科院分区：
文献类型：
--
作者：
LIAO, W;OU, JH
B型肝炎病毒核心蛋白（抗原）是B型肝炎病毒感染的重要血清学标志物。这种蛋白质存在于受感染肝细胞的细胞质或细胞核中，或两者中。核定位信号先前已被确定在核心蛋白序列。该信号与三个重复的SPRRR基序重叠。在这份报告中，我们证明，所有的丝氨酸残基在这三个SPRRR图案与丙氨酸tan的取代防止几乎完全的核心蛋白在Huh-7肝癌细胞的磷酸化，增强核定位的核心蛋白在Huh-7和非肝细胞，并取消细胞周期调节核定位的核心蛋白。由于三个核心蛋白突变体，保留只有一个丝氨酸残基的每一个的三个SPRRR基序可以磷酸化到类似的程度，这三个丝氨酸残基可能可以作为受体位点的磷酸化具有相同的效率。这些结果与观察到的三个SPRRR基序与核心蛋白的核定位信号重叠一起，提高了核心蛋白的核定位受SPRRR基序中丝氨酸残基的磷酸化负调控的可能性。
Hepatitis B virus core protein (antigen) is an important serologic marker of hepatitis B virus infection. This protein is found in the cytoplasm or the nuclei, or both, of infected hepatocytes. A nuclear localization signal has previously been identified in the core protein sequence. This signal overlaps three repeated SPRRR motifs. In this report, we demonstrate that substitution of all of the serine residues in these three SPRRR motifs with alanine tan prevent almost entirely the phosphorylation of the core protein in Huh-7 hepatoma cells, enhance nuclear localization of the core protein in both Huh-7 and nonhepatic cells, and abolish cell cycle regulation of nuclear localization of the core protein. Since the three core protein mutants which retained only one serine residue of each of the three SPRRR motifs could be phosphorylated to similar degrees, these three serine residues likely could serve as the acceptor sites for phosphorylation with equal efficiency. These results, together,vith the observation that the three SPRRR motifs overlap the nuclear localization signal of the core protein, raise the possibility that nuclear localization of the core protein is negatively regulated by phosphorylation of the serine residues in the SPRRR motifs.