Revisiting the "Cdk-centric" view of the mammalian cell cycle.
Since the early genetic studies in yeast, regulation of the cell cycle has been associated with the sequential activation of several proline-directed serine-threonine protein kinases by cyclins. From yeast to humans, the activity of these cyclin-dependent kinases (Cdks) have been thought to be essential for cell cycle regulation. Recent gene-targeted mouse models for different cyclins and Cdks have shown that members of these families show a certain level of redundancy and that specific complexes are not required for the mitotic cell cycle. However, the complexity of the Cdk-cyclin network and the promiscuity of their members makes it difficult to understand the relative contribution of these proteins to the mammalian cell division cycle. Compensatory roles by non-Cdk activities and Cdk-independent functions of cyclins are increasing the complexity of the current simplistic models. We still do not know whether at least one cyclin-dependent kinase activity is required for cell cycle progression in mammalian cells. Indeed, this is a relevant question for cancer therapy.
Malumbres
Marcos
M
Cell Division and Cancer Group, MolecularOncology Program, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain. mmm@cnio.es
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D016213:Cyclins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D016193:G1 Phase / Q000502:physiology; D051379:Mice; D008957:Models, Genetic; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology
D016213:Cyclins; D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases