Cyclin-dependent protein

Recent studies have concentrated on control mechanisms, such as the crucial part played by cyclin dependent protein kinases in triggering chromosome duplication and segregation (Nurse 1990) and surveillance mechanisms (checkpoints) that monitor the fidelity of these two processes (Hartwell Weinert 1989). This focus on control is however a recent phenomenon. Earlier studies, largely... 

Johnson LN, MoUner ED, Brown NR, et al. Structural studies with inhibitors of the cell cycle regulatory kinase cyclin-dependent protein kinase 2. Pharmacol Ther 2002 93 113-24. 

Nugroho, T. T., and Mendenhall, M. D. (1994). An inhibitor of yeast cyclin-dependent protein kinase plays an important role in ensuring the genomic integrity of daughter cells. Mol Cell Biol 14,3320-3328. 

Protein phosphatase I has a phosphorylation site at the C terminus. Phosphorylation at this site by a cyclin-dependent protein kinase inhibits the phosphatase activity. 

Active cyclin-dependent protein kinases are thus heterodimers in which the CDK subimit carries the catalytic activity and the other subunit, the cychn, performs an activating and specificity-determining function. 

Fig. 13.10. Regulation and attack points of inhibitors of cyclin-dependent protein kinases (CKIs) in mammals. The various CKIs are activated and regulated by different signals. Inhibitory activity of the CKIs is specific for the different CDKs and CDK-cyclin combinations. p53 tumor suppressor protein p53 TGPP transforming growth factor P pRb tumor suppressor protein pRb p21 p2icipi. p27- pl6 pl6 ° CDK cyclin-dependent protein kinase Cyc cyclin E2F trans-...

Cyclins and Cyclin-dependent Protein Kinases (CDKs)... 

Levels of Cyclin-Dependent Protein Kinases Oscillate... 

FIGURE 12-44 Regulation of CDK by phosphorylation and proteolysis. (a) The cyclin-dependent protein kinase activated at the time of mitosis (the M phase CDK) has a "T loop" that can fold into the substrate-binding site. When Thr150 in the T loop is phosphorylated, the loop moves out of the substrate-binding site, activating the CDK... 

Progression through the cell cycle is regulated by the cyclin-dependent protein kinases (CDKs), which act at specific points in the cycle, phosphorylating key proteins and modulating their activities. The catalytic subunit of CDKs is inactive unless associated with the regulatory cyclin subunit. 

Grant, P., Sharma, P., and Pant, H. C. (2001). Cyclin-dependent protein kinase 5 (Cdk5) and the regulation of neurofilament metabolism. Ewr. J. Biochem. 268, 1534-1546. 

Nigg, E. A., 1995, Cyclin-dependent protein kinases key regulators of the eukaryotic cell cycle. 

Shiekhattar R, Mermelstein F, Fisher RP et al (1995) Cdk-activating kinase complex is a component of human transcription factor TFIIH. Nature 374(6519) 283-287 Waters NC, Woodard CL, Prigge ST (2000) Cyclin H activation and drug susceptibility of the Pfinrk cyclin dependent protein kinase from Plasmodium falciparum. Mol Biochem Parasitol 107(l) 45-55 Xiao Z, Waters NC, Woodard CL et al (2001) Design and synthesis of Pfinrk inhibitors as potential antimalarial agents. Bioorg Med Chem Lett ll(21) 2875-2878 Woodard CL, Li Z, Kathcart AKet al (2003) Oxindole-based compounds are selective inhibitors of Plasmodium falciparum cyclin dependent protein kinases. J Med Chem 46(18) 3877-3882... 

Chen Y, Jirage D, Caridha D et al (2006) Identification of an effector protein and gain-of-fiinction mutants that activate Pfinrk, a malarial cyclin-dependent protein kinase. Mol Biochem Parasitol 149(1 ) 48-57 Woodard CL, Keenan SM, Gerena L et al (2007) Evaluation of broad spectrum protein kinase inhibitors to probe the architecture of the malarial cyclin dependent protein kinase Pfmrk. Bioorg Med Chem Lett 17(17) 4961-4966... 

Caridha D, Kathcart AK, Jirage D, Waters NC (2010) Activity of substituted thiophene sulfonamides against malarial and mammalian cyclin dependent protein kinases. Bioorg Med Chem Lett 20(13) 3863-3867 Geyer JA, Keenan SM, Woodard CL et al (2009) Selective inhibition of Pfinrk, a Plasmodium falciparum CDK, by antimalarial l,3-diaryl-2-propenones. Bioorg Med Chem Lett 19(7) 1982-1985 Jirage D, Chen Y, Caridha D et al (2010) The malarial CDK Pfinrk and its effector PfMATl phosphorylate DNA replication proteins and co-localize in the nucleus. Mol Biochem Parasitol 172(1) 9-18... 

CAT-REL, vesicular catecholamine release CB-R, cannabinoid receptor CB1-R, CB2-R, cannabinoid receptors CBD, chitin-binding domain CBG, cortisol-binding globulin CBZ-R, central benzodiazepine receptor CCK-R, cholecystokinin receptor CDC, chrysanthemum dicarboxylic acid CDK, cell division kinase, cyclin-dependent protein kinase... 

CDK1-CDK7, cyclin-dependent protein kinases 1-7... 

Cyclin-Cdks were appropriately named the cell cycle s engines . The cyclin-dependent protein kinases (Cdks) are soluble serine/threonine kinases of 34-40 kDa. The Cdks share with other serine/threonine protein kinases sequence similarities, including a subset of residues that is essential for catalytic activity. Cdks contribute the catalytic subunit, whereas the regulatory subunit is contributed by a cyclin. Cyclins control the kinase activity, determine the substrate specificity and the subcellular location of Cdks. Each of these processes is a potential site of regulation. The major substrates of the Cdks are proteins regulating gene transcription. Cdks can be controlled in three major ways ... 

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