Cyclins, Cdks, and Cyclin Kinase Inhibitors

After each mitotic cycle, a cell either remains in the cell cycle and divides once again, or withdraws from the cell cycle and adopts an alternative, nonproliferat-ing cell fate (e.g., quiescence or terminal differentia-tion). This "decision, " first called Start by Lee Hart-well and coworkers, was discovered and initially char-acterized by genetic analyses of the cell cycle of the yeast, Saccharomyces cerevisiae (Hartwell et al. 1974). Upon completion of Start, yeast become committed to complete the mitotic cycle and simultaneously initiate the parallel pathways leading to spindle pole body duplication, bud emergence, and DNA replication. An analogous et of events is thought o take place during the G t phase of the mammalian cell cycle (Zetterberg and Larson 1985), and this is often called the restric-tion point (Pardee 1974). Prior to the restriction point, but not after, the cell exits the celt cycle if specific mitogenic and growth signals are absent. Cells respond to both extracellular and intracellular cues when deciding to begin a new mitotic cycle (Fig. 1). Extracellular signals that promote cell proliferation include growth factors, mitogens, nutrients, and cell-substratum interactions. Examples of signals that cause withdrawal from the cell cycle are antimitogens