[The regulation of calmodulin in the cell cycle]

In order to study the role of calmodulin (CaM) in the cell cycle, RC 3 cells carring the CaM expression vectors which was constructed by joining the CaM cDNA with a plasmid of mouse mammary tumor virus (MMTV), were used in this experiment. The CaM expression vectors transcription is regulated by a dexamethasone (DXM) inducible MMTV LTR promoter. Upon addition of DXM, cells have transiently increased CaM mRNA and protein levels. Increased CaM caused a acceleration of proliferation. Flow cytometric analysis showed that progression though G1, G2 and metaphase was accelerated by increase in CaM levels, while treatment with the CaM antagonist trifluoperazine (TFP) blocked cell cycle progression at G1/S boundary and during G2/M and metaphase. The studies have shown that CaM is important in controlling progression at three points in the cell cycle: (1) The G1/S boundary to permit the initiation of DNA synthesis; (2) The G2/M boundary to permit the initiation of mitosis; (3) At the metaphase/anaphase transition of mitosis to permit chromosome segration and the completion of mitosis. This study indicates that the RC 3 cell is a useful experimental cell model for studing the effect of a transient increase of intracellular CaM levels on control of cell cycle.