CyclinB1 expression is elevated and mitosis is delayed in HeLa cells expressing autonomous CaMKII

• Published in: Cellular signalling Vol. 15; no. 11; pp. 1049 - 1057
• Main Authors: Beauman, Shirelyn R., Campos, Begoña, Kaetzel, Marcia A., Dedman, John R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.11.2003
• Subjects: Calcium Signaling - physiology; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Calcium/calmodulin-dependent protein kinase II; Calmodulin - metabolism; cdc2; Cell cycle; Cloning, Molecular; Cyclin B - metabolism; Cyclin B1; Enzyme Activation - physiology; Flow Cytometry; HeLa Cells; Humans; Interphase - physiology; Mitosis; Mitosis - physiology; Mutagenesis, Site-Directed; Phosphorylation; S Phase - physiology; Tet-on; Tet-on; Calcium/calmodulin-dependent protein kinase II; Mitosis; cdc2; Cyclin B1; Cell cycle
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/S0898-6568(03)00068-8

Calcium is a second messenger that is implicated in the regulation of cell cycle transitions. Calmodulin is a ubiquitous protein that translates intracellular calcium signals and activates several enzymes including calcium/calmodulin-dependent protein kinase II (CaMKII). Pharmacological inhibitors and constitutively active mutants have implicated CaMKII in cell cycle mediation. Specifically, constitutively active CaMKII impedes mitosis. In order to elucidate the molecular mechanisms underlying this phenomenon, the effect of constitutively active CaMKII gene expression on cdc2/cyclin B1 was investigated. As seen in previous studies with S. pombe, constitutively active CaMKII-hindered mitosis. However, this report shows that CaMKII does not cause permanent cell cycle arrest but delays progression into mitosis. Constitutive CaMKII expression also leads to elevations in cyclin B1 expression and cdc2 tyrosine-15 phosphorylation, analogous to observations in cells treated with hydroxyurea. Taken together, these data suggest that constitutive CaMKII may delay mitosis by activating a cell cycle checkpoint.