Calcium, calmodulin and cell proliferation

Calcium and calmodulin have been proposed to be regulatory factors in cell cycle progression. Clonal mouse cell lines harboring episomally-carried genes have been prepared to address this question. Some lines produce extra calmodulin, others express antisense RNA to decrease calmodulin, while others produce the Ca2+-buffering protein parvalbumin. The results show that calmodulin acts at two points in the cell cycle--the G1/S boundary and metaphase transition. An additional Ca2+ event that is calmodulin-independent occurs at mitotic prophase. The elevated (or depressed) level of intracellular Ca2+ binding protein does not markedly affect gene expression. In cells containing excess calmodulin, the synthesis mechanisms that normally control the level of calmodulin post-transcriptionally are overridden. Genes normally expressed in G1 whose products are involved in growth control show increases in calmodulin over producing cell lines. Elevated calmodulin decreases tubulin mRNA presumably due to its effect on microtubule stability. The availability of cell lines in which calmodulin can be inducibly increased or decreased should provide tools to elucidate the molecular mechanisms that govern the regulatory roles for this protein in cell cycle progression.