The role of cdc2 in the expression of herpes simplex virus genes
The role of cdc2 in the expression of herpes simplex virus genes
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DOI：
10.1073/pnas.200375297
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发表时间：
2000-09-26
影响因子：
11.1
通讯作者：
Roizman, B
中科院分区：
文献类型：
--
作者：
Advani, SJ;Weichselbaum, RR;Roizman, B
早期报告表明，cdc2 激酶在感染单纯疱疹病毒 1 的细胞中被激活，并且该激活主要由两种病毒蛋白介导，即受感染细胞蛋白 22 (ICP22) 和 U(L)13 编码的蛋白激酶。以 U(S)11 为例的晚期 (gamma(2)) 基因子集的最佳表达需要相同的蛋白质。在本研究中，我们使用显性失活 cdc2 蛋白来确定 cdc2 在病毒基因表达中的作用。我们报告如下。 (i) cdc2 显性失活蛋白对至少两种 α 调节蛋白（ICP4 和 ICP0）的合成和积累没有影响。两个 β 蛋白（核糖核苷酸还原酶主要亚基和单链 DNA 结合蛋白）和两个 yl 蛋白（糖蛋白 D 和病毒蛋白酶）。 U(S)11 是一种 γ(2) 蛋白，仅在无法检测到 cdc2 显性失活蛋白或产生量非常少的细胞中积累。 (ii)预计被cdc2磷酸化的氨基酸序列存在于至少27种病毒蛋白中，包括调节蛋白ICP4。 ICP0。和 ICP22。在体外测定中，我们证明cdc2特异性磷酸化由ICP0第二外显子组成的多肽，但不磷酸化包含第三外显子序列的多肽，正如序列分析所预测的那样。我们得出的结论是，cdc2 是 γ(2) 蛋白子集的最佳表达所必需的，其表达也受到介导 cdc2 激酶激活的病毒蛋白（ICP22 和 U(L)13）的调节。
Earlier reports have shown that cdc2 kinase is activated in cells infected with herpes simplex virus 1 and that the activation is mediated principally by two viral proteins, the infected cell protein 22 (ICP22) and the protein kinase encoded by U(L)13. The same proteins are required for optimal expression of a subset of late (gamma(2)) genes exemplified by U(S)11. In this study, we used a dominant-negative cdc2 protein to determine the role of cdc2 in viral gene expression. We report the following. (i) The cdc2 dominant-negative protein had no effect in the synthesis and accumulation of at least two alpha-regulatory proteins (ICP4 and ICP0). two beta-proteins (ribonucleotide reductase major subunit and single-stranded DNA-binding protein), and two yl-proteins (glycoprotein D and viral protease). U(S)11, a gamma(2)-protein, accumulated only in cells in which cdc2 dominant-negative protein could not be detected or was made in very small amounts. (ii) The sequence of amino acids predicted to be phosphorylated by cdc2 is present in at least 27 viral proteins inclusive of the regulatory proteins ICP4. ICP0. and ICP22. In in vitro assays, we demonstrated that cdc2 specifically phosphorylated a polypeptide consisting of the second exon of ICP0 but not a polypeptide containing the sequence of the third exon as would be predicted from the sequence analysis. We conclude that cdc2 is required for optimal expression of a subset of gamma(2)-proteins whose expression is also regulated by the viral proteins (ICP22 and U(L)13) that mediate the activation of cdc2 kinase.