Cyclin-dependent kinases at the G1-S transition of the mammalian cell cycle.
In the mammalian cell cycle, the transition from the G1 phase to S phase, in which DNA replication occurs, is dependent on tight cell size control and has been shown to be regulated by the cyclin-dependent kinases (Cdks) 2, 3, 4 and 6. Activities of Cdks are controlled by association with cyclins and reversible phosphorylation reactions. An additional level of regulation is provided by inhibitors of Cdks. G1-S and S phase substrates of these enzymes include proteins implicated in replication and transcription. Whereas the regulation and role of Cdk2, 4 and 6 has intensively been studied, less is known about Cdk3. Recent data provide first insights into the regulation of Cdk3-associate kinase activity and suggest a model how Cdk3 participates in the regulation of the G1-S transition. Although it has been shown that these G1-Cdks are absolutely essential for a proper transition into S phase, their physiological activation is not sufficient to directly initiate replication independently of cell size. Evidence obtained from yeast and Xenopus indicate the initiation of DNA replication to be a two-step process: the origin recognition complex, Cdc6 and Mcm proteins are required for establishing the prereplicative complex and the activities of Cdks and of Cdc7 kinase then trigger the G1-S transition. Recent findings provide evidence that the overall mechanism of initiation of replication is conserved in mammalian cells.
Hengstschläger
M
M
Obstetrics and Gynecology, Department of Prenatal Diagnosis and Therapy, University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. markus.hengstschlaeger@akh-wien.ac.at
Braun
K
K
Soucek
T
T
Miloloza
A
A
Hengstschläger-Ottnad
E
E
D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016193:G1 Phase; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase; D014157:Transcription Factors / Q000502:physiology
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors; D018844:Cyclin-Dependent Kinases