Identification of stimulators and inhibitors of Cdc7 kinase in vitro
| Autor: | Chika Taniyama, Hisao Masai, Naoko Kakusho |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
DNA Replication
Enzyme Activators Cell Cycle Proteins DNA-Directed DNA Polymerase Mitogen-activated protein kinase kinase Protein Serine-Threonine Kinases Biochemistry MAP2K7 Cell Line Histones Multienzyme Complexes Animals Humans ASK1 Kinase activity Phosphorylation Molecular Biology Protein Kinase Inhibitors biology Cyclin-dependent kinase 2 Biogenic Polyamines Nuclear Proteins Cell Biology Protein kinase R Chromatin Minichromosome Maintenance Complex Component 4 DNA-Binding Proteins Enzyme Activation Cyclin-dependent kinase complex biology.protein Cyclin-dependent kinase 9 |
| Zdroj: | The Journal of biological chemistry. 283(28) |
| ISSN: | 0021-9258 |
| Popis: | Cdc7 is a serine-threonine kinase that regulates initiation and progression of DNA replication. The activity of purified Cdc7 kinase is significantly stimulated by polyamines such as spermine or spermidine. Positively charged polymers of lysine or arginine also stimulate its kinase activity, whereas the negatively charged substances such as polyglutamate or nucleic acids significantly inhibit the kinase activity. Spermine affects both the K(m) and V(max) of Cdc7 kinase for a minichromosome maintenance (MCM) substrate. We also found that histones, lysine- and arginine-rich basic proteins, can stimulate Cdc7 kinase activity, and a MCM complex in association with histone is a more efficient substrate of Cdc7 than the free MCM complex. These results identify potential cellular inhibitors and stimulators of Cdc7 kinase and suggest that Cdc7 may be another target of cellular polyamines and that histones may stimulate Cdc7-mediated phosphorylation of chromatin-bound substrates. Ectopic expression of an antizyme, known to reduce the cellular polyamine levels, resulted in reduction of Cdc7-mediated phosphorylation of MCM4 protein, suggesting physiological roles of polyamines in regulation of Cdc7 kinase activity in the cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|