Department of Cell Biology, 1900 University Blvd, Birmingham, AL 35294, USA.
Department of Pediatrics, University of Alabama at Birmingham, 1600 6th Avenue South, Birmingham, AL 35233, USA.
J Gen Virol. 2012 Aug;93(Pt 8):1743-1755. doi: 10.1099/vir.0.039214-0. Epub 2012 May 2.
The UL97 protein kinase is a serine/threonine kinase expressed by human cytomegalovirus (CMV) that phosphorylates ganciclovir. An investigation of the subcellular localization of pUL97 in infected cells indicated that, early in infection, pUL97 localized to focal sites in the nucleus that transitioned to subnuclear compartments and eventually throughout the entire nucleus. When UL97 kinase activity was eliminated with a K355M mutation or pharmacologically inhibited with maribavir, the expansion and redistribution of pUL97 foci within the nucleus was delayed, nuclear reorganization did not occur and assembly complexes in the cytoplasm failed to form normally. As UL97 kinase and its homologues appear to be functionally related to CDK1, a known regulator of nuclear structural organization, the effects of the UL97 kinase on CDK1 were investigated. Expression of CDK1 in infected cells appeared to be induced by UL97 kinase activity at the level of transcription and was not tied to other virus life-cycle events, such as viral DNA replication or virion assembly. These results suggest that, in addition to phosphorylating CDK1 targets, the UL97 kinase modifies G₂/M cell-cycle checkpoint regulators, specifically CDK1, to promote virus replication.
UL97 蛋白激酶是一种由人类巨细胞病毒 (CMV) 表达的丝氨酸/苏氨酸激酶，可磷酸化更昔洛韦。对感染细胞中 pUL97 的亚细胞定位的研究表明，在感染早期，pUL97 定位于核内的焦点部位，然后转移到亚核区室，最终遍布整个细胞核。当用 K355M 突变消除 UL97 激酶活性或用马拉韦罗进行药理学抑制时，pUL97 焦点在核内的扩展和重新分布会延迟，核重组不会发生，细胞质中的组装复合物也不能正常形成。由于 UL97 激酶及其同源物似乎在功能上与 CDK1 相关，后者是核结构组织的已知调节剂，因此研究了 UL97 激酶对 CDK1 的影响。感染细胞中 CDK1 的表达似乎是由 UL97 激酶活性在转录水平诱导的，与其他病毒生命周期事件（如病毒 DNA 复制或病毒粒子组装）无关。这些结果表明，除了磷酸化 CDK1 靶标外，UL97 激酶还修饰 G₂/M 细胞周期检查点调节剂，特别是 CDK1，以促进病毒复制。
