Detection of Cyclins in Individual Cells by Flow and Laser Scanning Cytometry
Progression of cells through successive phases and checkpoints of the cell cycle is maintained by sequential phosphorylation of different sets of nuclear and cytoplasmic proteins by cyclin-dependent kinases (CDKs) (1 –12 ). By activating their partner CDKs and targeting them to the respective protein substrates cyclins play a key regulatory role in this process. Cyclins Bl, A, E, and D are expressed discontinuously during the cycle. The synthesis and degradation of these cyclins occurs at well-defined time points of the cell cycle (Table 1 ). Table 1 Cyclins and Their Partner CDKs During the Cell Cycle
Cyclin | Primary CDK partner(s) | Presumed role in cell cycle | Peak of expression | Localization |
---|---|---|---|---|
D type | CDK4 and CDK6 | pRB phosphorylation, commitment to S phase | Early in G1 | Nucleus |
E | CDK2 | Initiation of S | G1/ S transition | Nucleus |
A | CDK2 and CDC2 | S and G2 traverse | During G2M | Nucleus |
Bl | CDC2 | G2 traverse entrance to M | Late G2/M | Cytoplasm/Nucleusa |
a Cyclin B1 is localized in cytoplasm during G2 and undergoes translocation to nucleus during prophase