Regulation of Cell Cycle Entry and Exit: A Single Cell Perspective

The transition between proliferating and quiescent states must be carefully regulated to ensure that cells divide to create the cells an organism needs only at the appropriate time and place. Cyclin-dependent kinases (CDKs) are critical for both transitioning cells from one cell cycle state to the next, and for regulating whether cells are proliferating or quiescent. CDKs are regulated by association with cognate cyclins, activating and inhibitory phosphorylation events, and proteins that bind to them and inhibit their activity. The substrates of these kinases, including the retinoblastoma protein, enforce the changes in cell cycle status. Single cell analysis has clarified that competition among factors that activate and inhibit CDK activity leads to the cell's decision to enter the cell cycle, a decision the cell makes before S phase. Signaling pathways that control the activity of CDKs regulate the transition between quiescence and proliferation in stem cells, including stem cells that generate muscle and neurons. © 2020 American Physiological Society. Compr Physiol 10:317-344, 2020.