title: Human cytomegalovirus UL97 kinase alters the accumulation of CDK1.
abstract: 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.
authors.affiliation: Department of Cell Biology, 1900 University Blvd, Birmingham, AL 35294, USA.
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Gill
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, 1600 6th Avenue South, Birmingham, AL 35233, USA.
authors.forename: Scott H
authors.initials: SH
authors.lastname: James
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, 1600 6th Avenue South, Birmingham, AL 35233, USA.|Department of Cell Biology, 1900 University Blvd, Birmingham, AL 35294, USA.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Prichard
mesh_terms: D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D016203:CDC2 Protein Kinase