Cell cycle progression without cyclin E/CDK2: breaking down the walls of dogma.
G1 is the phase of the cell cycle wherein the cell is responsive to growth factor-dependent signals. As such, G1 regulation is frequently disrupted in cancer through deregulation of cyclin/CDK activity; deregulation of G1 phase provides tumorigenic cells with a growth advantage. Cyclin E, the regulatory cyclin for CDK2, is considered a requisite regulator of G1 progression. Cyclin E is overexpressed in cancer, suggesting that cyclin E/CDK2 deregulation contributes to tumorigenesis. Two papers now challenge both the concept that cyclin E/CDK2 is a requisite component of the cell cycle machine and efforts to develop cyclin E/CDK2 inhibitors as antiproliferative therapeutics.
Gladden
Andrew B
AB
The Leonard and Madlyn Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Family Cancer Center of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Diehl
J Alan
JA
D000818:Animals; D042846:CDC2-CDC28 Kinases / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D056741:Cyclin D; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology; D016193:G1 Phase / Q000502:physiology; D051379:Mice; D008958:Models, Molecular; D011518:Proto-Oncogene Proteins; D016196:S Phase / Q000502:physiology
D056741:Cyclin D; D019927:Cyclin E; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; C495902:Cdk4 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases