CALMODULIN-DEPENDENT PROTEIN-KINASE-II IS REQUIRED FOR G(1)/S PROGRESSION IN HELA-CELLS

Calmodulin (CaM) has been previously shown to be essential for cell cycle progression in eukaryotic cells, being required at the G(1)/S,G(2)/M, and metaphase-anaphase transitions. Little is known about the specific CaM-dependent enzymes that mediate Ca2+/CaM signaling to affect cell proliferation. In this study we show that inhibition of calmodulin kinase II (CaMKII) in HeLa cells using the CaMKII inhibitor KN-93 causes cell cycle arrest, demonstrating that CaMKII is required for cell cycle progression. Detailed analysis of arrest cells suggests that CaMKII is required for the initiation of DNA synthesis. Cells treated with KN-93 arrest with a G(1) DNA content, but with elevated cyclin-dependent histone H1 kinase activity, suggesting that CaMKII may act at a point very close to the onset of DNA synthesis in mammalian cells.