Regulation of the Cell Cycle by Calcium and Calmodulin

IN ORDER to reproduce and multiply, every cell must execute an orderly series of events, generally called the cell cycle, at some time during its life span. The cell cycle was first thought to consist of mitosis and interphase as determined from morphological analysis. As new techniques were developed, a period of DNA synthesis, the S phase, was detected; this was temporally separated from the previous mitosis by a “gap,” the G1 phase, and from the subsequent mitosis by another “gap,” the G2 phase (Fig. 1). The G1 phase is the decision phase in which cells either commit to undergo another round of DNA synthesis and continue to cycle or to exit the cell cycle to enter a quiescent state frequently referred to as G0. Cells in the G0 phase either terminally differentiate or resume proliferation upon addition of an appropriate mitogen (Fig. 1). When DNA synthesis is completed, cells normally proceed to mitosis. The regulation of this series of events is of primary interest to the endocrinologist, since precise control of cell fate is an essential element in hormone action. During the last decade, genetic analyses in fungi and biochemical studies in vertebrate and invertebrate species have resulted in identification of key regulatory proteins that specifically control progression through the decision points of the cell cycle. However, the overall process is very complicated, and control of cell proliferation is a result of a coordinated regulation of multiple biochemical pathways that integrate both intracellular and extracellular signals. Many critical components of these pathways remain to be elucidated.