title: Animal Models for Studying the In Vivo Functions of Cell Cycle CDKs.
abstract: Multiple Cdks (Cdk4, Cdk6, and Cdk2) and a mitotic Cdk (Cdk1) are involved in cell cycle progression in mammals. Cyclins, Cdk inhibitors, and phosphorylations (both activating and inhibitory) at different cellular levels tightly modulate the activities of these kinases. Based on the results of biochemical studies, it was long believed that different Cdks functioned at specific stages during cell cycle progression. However, deletion of all three interphase Cdks in mice affected cell cycle entry and progression only in certain specialized cells such as hematopoietic cells, beta cells of the pancreas, pituitary lactotrophs, and cardiomyocytes. These genetic experiments challenged the prevailing biochemical model and established that Cdks function in a cell-specific, but not a stage-specific, manner during cell cycle entry and the progression of mitosis. Recent in vivo studies have further established that Cdk1 is the only Cdk that is both essential and sufficient for driving the resumption of meiosis during mouse oocyte maturation. These genetic studies suggest a minimal-essential cell cycle model in which Cdk1 is the central regulator of cell cycle progression. Cdk1 can compensate for the loss of the interphase Cdks by forming active complexes with A-, B-, E-, and D-type Cyclins in a stepwise manner. Thus, Cdk1 plays an essential role in both mitosis and meiosis in mammals, whereas interphase Cdks are dispensable.
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, 462, 405 30, Gothenburg, Sweden, sanjiv.risal@gu.se.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Risal
authors.forename: Deepak
authors.initials: D
authors.lastname: Adhikari
authors.forename: Kui
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D006801:Humans; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D023421:Models, Animal; D009865:Oocytes / Q000201:enzymology; D010766:Phosphorylation
chemical_list: D016203:CDC2 Protein Kinase; C495893:Cdk2 protein, mouse; C495902:Cdk4 protein, mouse; C495912:Cdk6 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases