Cydin inhibitor

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

ScHWOB, E., et al.. The B-type cydin kinase inhibitor p40SICl controls the... 

Knockaert M, Greengard P, Meijer L. Pharmacological inhibitors of cydin-dependent kinases. Trends Pharmacol Sci 2002 23 417-25. 

Terrell J, Shih S, Dunn R, Hicke L (1998) A function for monoubiquitination in the internalization of a G protein-coupled receptor. Mol Cell 1 193-202 Tomoda K, Kubota Y, Kato J (1999) Degradation of the cydin-dependent-kinase inhibitor p27 is instigated by Jabl. Nature 398 160-165 Toyoshima F, Moriguchi T, Wada A, Fukuda M, Nishida, E (1998) Nudear export of cydin Bl and its possible role in the DNA damage-induced G2 checkpoint. EMBO J 17 2728-2735... 

Chau, V., Yew, P.R., Dhaetta, G.F., Rolee, M., Role of the ubiquitm-protea-some pathway in regulating abundance of the cydin-dependent kinase inhibitor p27. Science 1995, 269, 682-685. 

Progress of the cycle in Gj phase is controlled in particular by the cyclins of types D and E and by inhibitors of the CDKs. The two types of cyclins perform different functions during Gv Whereas the cylin D-CDK2/4 complexes prepare the cell for crossing R, the decision for passage through R and entry into S phase is critically dependent on the activity of cydin E-CDK2 complexes (Fig. 13.14). 

Stiegler, P. and Giordano, A. (2001) The family of retinoblastoma proteins. Crit Rev.Eukaryot.Gene Expr., 11, 59-76. Tomoda, K., Kubota, Y. and Kato, J. (1999) Degradation of the cydin-dependent-kinase inhibitor p27Kipl is instigated by Jabl. Nature, 398, 160-165. 

Histone acetylation and deacetylation are catalyzed by histone acetyltransferases (HATs) and HDACs, respectively, and play important roles in transcriptional regulation. Inhibitors of these enzymes are known to induce cell cycle arrest,p53-independent induction of the cydin-dependent kinase inhibitor... 

For example, TSA was found to reduce the expression of cydin Bl, a key cyclin for G2-M transition, but in fact also stimulated expression of p2 Cip/WAF an inhibitor of cyclin-dependent kinase (CDK) and Cdc2. Through TSA-mediated HDAC inhibition, the G2-M transition is blocked because of... 

Inhibitor of cydin dependent kinases inhibition of Bd-2 expression upregulation of death receptor Fas, some DNA intercalation activation of caspase-3 DNA fragmentation depolarization of mitochondrial membranes, apoptotic Apoptotic inhibition of p53 phosphorylation inhibition of cdk2 kinase... 

Hahntow, I.N., Schneller, F., Oelsner, M., Weick, K., Ringhausen, L, Fend, F Reschel, C and Deckert, T. (2004) Cydin-dependent kinase inhibitor Roscovitine induces apoptosis in chronic lymphocytic leukemia cells. Leukemia, 18, 747-755. 

Meriolins are potent inhibitors of CDKs especially meriolin 1 (R = H), merioUn 2 (R = OH), meriolin 3 (R = OMe), meriolin 4 (R = OEt), and meriolin 5 (R = OPr) for CDKl/cyclin B, CDK2/cydin A, and CDK9/cyclin T with IC50 values <0.1 pM. Currently, 14 meriolins have been synthesized and tested for their CDK inhibitory activity (Echalier et cd., 2008). 

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