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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells
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Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells

机译：REST / CoREST /组蛋白脱乙酰基酶阻遏物复合物的成分在HSV-1感染的细胞中被破坏，修饰和转移

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摘要

The infected cell protein (ICP)O enables gene expression and the replication of herpes simplex virus (HSV)-1 in cells infected at low multiplicities and enhances the expression of genes introduced into cells by transfection or infection. We report that a short sequence of ICPO is similar to a sequence in the amino terminus of CoREST, a corepressor that exists in complexes with the repressor REST and histone deacetylases (HDACs) 1 or 2 to repress cellular gene expression. In wild-type-virus-infected cells, HDAC1 dissociates from the CoREST/REST complex, CoREST and HDAC1 are phosphorylated by a process mediated by viral protein kinases, and CoREST and HDAC1 are partially translocated to the cytoplasm. In cells infected with a virus mutant (ΔICP4), in which ICPO accumulates, but post-α gene expression is blocked, HDAC1 is dissociated from the CoREST/REST complex, but translocation to the cytoplasm does not occur. After infection with a mutant virus from which ICPO is deleted, the complex remains intact, but, under conditions of productive infection, the complex is partially translocated to the cytoplasm. These results suggest that, at low multiplicities of infection, ICPO blocks CoREST-mediated silencing of viral genes by dissociation of HDAC1, whereas subsequent modifications and translocation of the components of the complex are the functions of other viral gene products made later in infection.
机译：感染的细胞蛋白（ICP）O可在低多重感染的细胞中实现基因表达和单纯疱疹病毒（HSV）-1的复制，并增强通过转染或感染引入细胞的基因的表达。我们报告说，ICPO的短序列与CoREST氨基末端的序列相似，Copress是与阻遏物REST和组蛋白脱乙酰基酶（HDACs）1或2形成复合物以抑制细胞基因表达的复合物。在野生型病毒感染的细胞中，HDAC1从CoREST / REST复合体解离，CoREST和HDAC1被病毒蛋白激酶介导的过程磷酸化，CoREST和HDAC1部分转移到细胞质中。在感染了ICPO的病毒突变体（ΔICP4）感染的细胞中，但后α基因表达受阻，HDAC1从CoREST / REST复合物中解离，但不会发生向细胞质的转运。在用删除了ICPO的突变病毒感染后，复合物保持完整，但是在生产性感染的条件下，复合物部分转移到细胞质中。这些结果表明，在低感染复数下，ICPO通过解离HDAC1阻断CoREST介导的病毒基因沉默，而复合物成分的后续修饰和易位是后来感染其他病毒基因产物的功能。

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