Revisiting the "Cdk-centric" view of the mammalian cell cycle

Cell Cycle. 2005 Feb;4(2):206-10. doi: 10.4161/cc.4.2.1406. Epub 2005 Feb 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / physiology*
  • Cell Division / physiology
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / physiology*
  • Cyclins / physiology*
  • Enzyme Inhibitors / therapeutic use
  • G1 Phase / physiology
  • Mice
  • Models, Genetic
  • Neoplasms / drug therapy
  • Neoplasms / pathology

Substances

  • Cyclins
  • Enzyme Inhibitors
  • Cyclin-Dependent Kinases