Cyclin-dependent kinase cell cycle regulation

Control of the various phases of the growth cyde is exerted by the cyclical activation and repression of the cyclin-dependent kinases. Two important regulators of the cell cycle have been now shown to participate in acute renal failure. One family of proteins, the cycUn-dependent kinase inhibitors, which bind to and inhibit assembled cyclin kinases, and in particular the cycUn-dependent kinase inhibitor protein p21 is expressed in all forms of renal failure studied, induding ischemia-reperfusion, cisplatin and obstructive uropathy. This protein binds to and inhibits the CDKs that regulate the Gl/S a G2/M transition. P21 expression is enhanced by hostile environmental conditions [82]. The function of these checkpoints is to monitor the fidelity of DNA rephcation and other macromolecular components of the cell necessary for accurate reproduction... 

Rb Tumor Suppressor 22 p53 and p53-Dependent Cell Cycle Checkpoints 22 Role of Cyclin-Dependent Kinases in the Regulation of Cell Cycle and Apoptosis 23... 

Cell Cycle Control. Figure 1 Cell cycle regulation by Cyclin dependent kinases (CDKs). Different cyclins bound to different CDKs promote the transition from one cell cycle phase into another. CDK-dependent phosphorylation of Rb is required to release active E2F transcription factors, which promotes entry into S phase. 

Hong Y, Roy R, Ambros V 1998 Developmental regulation of a cyclin-dependent kinase inhibitor controls postembryonic cell cycle progression in Caenorhabditis elegant. Development 125 3585—3597... 

Cell cycle is one of the physiological processes in which the role of uhiquitin—proteasome-mediated proteolysis is well established. With the advent of yeast mutants that interfered with various phases of the cell cycle, cyclin-dependent kinases (Cdks) were found to have a critical role in regulating the cell cycle. Typically, Cdks activated hy regulatory proteins are known as cyclins. Different Cdk—cyclin complexes are formed at specific stages of the cell cycle such as the S-phase (in which DNA synthesis occurs) and the metaphase. The transition from metaphase to anaphase depends on degradation of cyclins. " " Systematic biochemical studies showed that cyclins were substrates for the uhiquitin—proteasome pathway (Table 5). 

Cell Cycle Regulation by Cyclin-Dependent Kinases... 

Hengst, L., Dulic, V., Slingerland, J., Lees, E., and Reed, S. (1994). A cell cycle regulated inhibitor of cyclin-dependent kinases, Proc Natl Acad Sci USA 91, 5291-5295. 

Casagrande, F. and Darbon, J.M., Effects of structurally related flavonoids on cell cycle progression of human melanoma cells regulation of cyclin-dependent kinases CDK2 and CDKl, Biochem. Pharmacol, 61, 1205, 2001. 

S. Chakravarty, S. Dugar (2002). Inhibitors of p38a MAL kinase. A m<. Rep. Med. Chem. 37 111. Y. Dai, S. Grant (2003). Cyclin-dependent kinase inhibitors. Curr. Opin. Pharmacol. 3 362-370. S. D. Kimball, K. R. Webster (2001). Cell cycle kinases and checkpoint regulation in cancer. Annu. Rep. Med. Chem. 36 139. 

Sielecki, T.M., Boylan, J.F., Benfield, P.A., Trainor, G.L. Cyclin-dependent kinase inhibitors useful targets in cell cycle regulation. Journal of Medicinal Chemistry 2000, 43, 1-18. 

In 1966 Fischer and Krebs published their seminal work on protein phosphorylation and its regulatory function in cellular pathways.1 Since then, great strides have been made in our understanding of protein kinases, their functional roles in cellular processes, and their pathogenic roles in diseases. Bishop and Varmus received the 1989 Nobel Prize for their work on oncogenic kinases.2 In 2001, Nurse and Hunt were also awarded the Nobel Prize for their work in elucidating the role of cyclins and cyclin-dependent kinases in regulating cell cycles.3... 

Recently considerable attention has been focused on the metabolites belonging to bisindolylmaleimides such as staurosporine (28) [12], UCN-01 (29) [13], rebeccamycin (30) [14], which were produced by the family of Streptomyces, Actinomycetes, and Saccharothrixes. These metabolites cause topoisomerase I mediated DNA cleavage, potent inhibition of protein kinase C and cell-cycle-regulating cyclin-dependent kinase (CDK), and cell-cycle checkpoint inhibition [15]. It seems interesting that myxomycetes also contain the bisindole metabolites having related structures to 28 - 30. 

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