THE ROLE OF CALCIUM IN THE CELL-CYCLE - FACTS AND HYPOTHESES

The regulation of cell cycle progression is a complex process which in volves kinase cascades, protease action, production of second messenge rs and other operations. Increasing evidence now compellingly suggests that changes in the intracellular Ca2+ concentration may also have a crucial role. Ca2+ transients occur at the awakening from quiescence, at the G/S transition, during S-phase, and at the exit from mitosis. T hey may lead to the activation of Ca2+ binding proteins like S-100, bu t the key decoder of the Ca2+ signals in the cycle is calmodulin. Acti vation of calmodulin leads to the stimulation of protein kinases, i.e. , CaM-kinase II, and of the CaM-dependent protein phosphatase calcineu rin. Ample evidence now indicates the G/S transition, the progression from G2 to M, and the metaphase/anaphase transition as specific points of intervention of CaM-kinase II. Another attractive possibility for the role of Ca2+ in the cycle is through the activation of the Ca2+-de pendent protease calpain: other proteases (e.g., the proteasome) have been suggested to be responsible for the degradation of some of cyclin s, which is essential to the progression of the cycle. One of the cycl ins, however, (D1) is instead degraded by calpain, which has been show n to promote both mitosis and meiosis when injected into somatic cells or oocytes. (C) 1998 Academic Press.