Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Autoantigens / biosynthesis
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CDC2 Protein Kinase / biosynthesis
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CDC2-CDC28 Kinases*
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Calcium / pharmacology
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Calmodulin / pharmacology*
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Cells, Cultured
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases*
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Cyclins / biosynthesis*
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DNA / biosynthesis
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DNA Polymerase II / biosynthesis*
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DNA Replication* / drug effects
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Electrophoresis, Polyacrylamide Gel
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Gene Expression / drug effects
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Humans
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Kinetics
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Lymphocyte Activation*
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Nuclear Proteins / biosynthesis
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Proliferating Cell Nuclear Antigen
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Protein Kinases / biosynthesis*
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Protein Kinases / isolation & purification
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins*
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
Substances
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Autoantigens
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Calmodulin
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Cyclins
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Nuclear Proteins
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Proliferating Cell Nuclear Antigen
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Proto-Oncogene Proteins
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DNA
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Protein Kinases
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Protein Serine-Threonine Kinases
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CDC2 Protein Kinase
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CDC2-CDC28 Kinases
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CDK2 protein, human
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CDK4 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases
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DNA Polymerase II
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Calcium