title: Phosphorylation of retinoblastoma protein by viral protein with cyclin-dependent kinase function.
abstract: As obligate intracellular parasites, viruses expertly modify cellular processes to facilitate their replication and spread, often by encoding genes that mimic the functions of cellular proteins while lacking regulatory features that modify their activity. We show that the human cytomegalovirus UL97 protein has activities similar to cellular cyclin-cyclin-dependent kinase (CDK) complexes. UL97 phosphorylated and inactivated the retinoblastoma tumor suppressor, stimulated cell cycle progression in mammalian cells, and rescued proliferation of Saccharomyces cerevisiae lacking CDK activity. UL97 is not inhibited by the CDK inhibitor p21 and lacks amino acid residues conserved in the CDKs that permit the attenuation of kinase activity. Thus, UL97 represents a functional ortholog of cellular CDKs that is immune from normal CDK control mechanisms.
authors.affiliation: Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Hume
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Finkel
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Kamil
authors.forename: Donald M
authors.initials: DM
authors.lastname: Coen
authors.forename: Michael R
authors.initials: MR
authors.lastname: Culbertson
authors.forename: Robert F
authors.initials: RF
authors.lastname: Kalejta
mesh_terms: D002453:Cell Cycle; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003587:Cytomegalovirus / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D018716:Molecular Mimicry; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D016160:Retinoblastoma Protein; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D018844:Cyclin-Dependent Kinases