title: The influence of reactive oxygen species on cell cycle progression in mammalian cells.
abstract: Cell cycle regulation is performed by cyclins and cyclin dependent kinases (CDKs). Recently, it has become clear that reactive oxygen species (ROS) influence the presence and activity of these enzymes and thereby control cell cycle progression. In this review, we first describe the discovery of enzymes specialized in ROS production: the NADPH oxidase (NOX) complexes. This discovery led to the recognition of ROS as essential players in many cellular processes, including cell cycle progression. ROS influence cell cycle progression in a context-dependent manner via phosphorylation and ubiquitination of CDKs and cell cycle regulatory molecules. We show that ROS often regulate ubiquitination via intermediate phosphorylation and that phosphorylation is thus the major regulatory mechanism influenced by ROS. In addition, ROS have recently been shown to be able to activate growth factor receptors. We will illustrate the diverse roles of ROS as mediators in cell cycle regulation by incorporating phosphorylation, ubiquitination and receptor activation in a model of cell cycle regulation involving EGF-receptor activation. We conclude that ROS can no longer be ignored when studying cell cycle progression.
authors.affiliation: University College Utrecht, P O Box 80145, 3508 TC Utrecht, The Netherlands.
authors.forename: Eline Hendrike
authors.initials: EH
authors.lastname: Verbon
authors.forename: Jan Andries
authors.initials: JA
authors.lastname: Post
authors.forename: Johannes
authors.initials: J
authors.lastname: Boonstra
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008322:Mammals; D008954:Models, Biological; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D054875:Ubiquitination; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D017382:Reactive Oxygen Species; D066246:ErbB Receptors; D018844:Cyclin-Dependent Kinases; D020687:cdc25 Phosphatases