Santella L
Laboratory of Cell Biology, Stazione Zoologica A. Dohrn, Napoli, Italy.
Biochem Biophys Res Commun. 1998 Mar 17;244(2):317-24. doi: 10.1006/bbrc.1998.8086.
The regulation of cell cycle progression is a complex process which involves kinase cascades, protease action, production of second messengers 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. They may lead to the activation of Ca2+ binding proteins like S-100, but the key decoder of the Ca2+ signals in the cycle is calmodulin. Activation of calmodulin leads to the stimulation of protein kinases, i.e., CaM-kinase II, and of the CaM-dependent protein phosphatase calcineurin. 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 Ca(2+)-dependent protease calpain: other proteases (e.g., the proteasome) have been suggested to be responsible for the degradation of some of cyclins, which is essential to the progression of the cycle. One of the cyclins, however, (D1) is instead degraded by calpain, which has been shown to promote both mitosis and meiosis when injected into somatic cells or oocytes.
细胞周期进程的调控是一个复杂的过程，涉及激酶级联反应、蛋白酶作用、第二信使的产生及其他活动。越来越多的证据有力地表明，细胞内钙离子浓度的变化可能也起着关键作用。钙离子瞬变发生在从静止状态苏醒时、G/S转换期、S期以及有丝分裂退出时。它们可能导致钙结合蛋白如S-100的激活，但细胞周期中钙离子信号的关键解码蛋白是钙调蛋白。钙调蛋白的激活会导致蛋白激酶即钙调蛋白激酶II以及钙调蛋白依赖性蛋白磷酸酶钙神经素的刺激。现在有充分的证据表明，G/S转换期、从G2期到M期的进程以及中期/后期转换是钙调蛋白激酶II的特定干预点。钙离子在细胞周期中发挥作用的另一个有吸引力的可能性是通过激活钙依赖性蛋白酶钙蛋白酶：有人提出其他蛋白酶（如蛋白酶体）负责某些细胞周期蛋白的降解，这对细胞周期的进程至关重要。然而，其中一种细胞周期蛋白（D1）却是由钙蛋白酶降解的，当将其注入体细胞或卵母细胞时，已证明它能促进有丝分裂和减数分裂。
