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 cy cle progression in eukaryotic cells, being required at the G(1)/S,G(2) /M, and metaphase-anaphase transitions. Little is known about the spec ific CaM-dependent enzymes that mediate Ca2+/CaM signaling to affect c ell proliferation. In this study we show that inhibition of calmodulin kinase II (CaMKII) in HeLa cells using the CaMKII inhibitor KN-93 cau ses cell cycle arrest, demonstrating that CaMKII is required for cell cycle progression. Detailed analysis of arrest cells suggests that CaM KII is required for the initiation of DNA synthesis. Cells treated wit h KN-93 arrest with a G(1) DNA content, but with elevated cyclin-depen dent histone H1 kinase activity, suggesting that CaMKII may act at a p oint very close to the onset of DNA synthesis in mammalian cells.