Calmodulin regulates the expression of cdks, cyclins and replicative enzymes during proliferative activation of human T lymphocytes.
Cell cycle is regulated by the activation of complexes of cyclins and cyclin-dependent protein kinases at specific points. Quiescent cells lack both cyclins and cyclin-dependent kinases but their expression is induced after proliferative activation. Cyclin A/cdk2 complexes are involved in the onset of DNA replication whereas cyclin B/cdc2 trigger mitosis. We report here that Ca2+ and calmodulin regulate the expression of cdk2, cdc2, cyclin B and the proliferating cell nuclear antigen (a co-factor of DNA polymerase-delta) in human T lymphocytes. Likewise, the expression of cdk4, cyclin A and DNA polymerase-alpha is dependent of the synergistic effect of both the Ca2+/calmodulin and the protein kinase C pathways. Thus, calmodulin controls DNA synthesis by regulating the levels of cdk2 and proliferating cell nuclear antigen and mitosis entry by modulating the expression of cyclin B and cdc2.
Colomer
J
J
Department of Cell Biology, Faculty of Medicine, University of Barcelona, Spain.
López-Girona
A
A
Agell
N
N
Bachs
O
O
D001324:Autoantigens / Q000096:biosynthesis; D016203:CDC2 Protein Kinase / Q000096:biosynthesis; D042846:CDC2-CDC28 Kinases; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology*; D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis; D004257:DNA Polymerase II / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D009687:Nuclear Proteins / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen; D011494:Protein Kinases / Q000096:biosynthesis* / Q000302:isolation & purification; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
D001324:Autoantigens; D002147:Calmodulin; D016213:Cyclins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D004247:DNA; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D004257:DNA Polymerase II; D002118:Calcium