Cyclin-dependent kinases humans

Desai, D Gu, Y and Morgan, D. O. (1992). Activation of human cyclin-dependent kinases in vitro. Mol. Biol. Cell 3 571-582. 

Abstract Inhibitors of the kinases controlling the cell cycle have emerged as an important therapeutic modality for the treatment of cancer. Drug discovery efforts have focused on inhibitors of the cyclin-dependent kinases, the Aurora kinases, and Polo-like kinases. Agents for each kinase are now advancing in human clinical trials. In this review we will summarize the work in this area with special emphasis on the structural biology and structure-activity relationships developed for the many chemotypes explored. 

Starfish and human cycline-dependent kinases (CDKs) Indimbin-3 -monoxime inhibits CDKs with IC50 =0.18 irM 133... 

Zi, X.L. et al., A flavonoid antioxidant, silymarin, inhibits activation of erbBl signaling and induces cyclin-dependent kinase inhibitors, G1 arrest and anticarcinogenic effects in human prostate carcinoma DU145 cells, Cancer Res., 58, 1920, 1998. 

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. 

Aggarwal BB, Banerjee S, Bharadwaj U, Sung B, Shishodia S, Sethi G. 2007. Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines. Biochem Pharmacol 73 1024-1032. 

An inhibitor of cyclin-dependent kinase 2, an enzyme implicated in a number of human cancers, has been developed through a simple application of dynamic... 

GTPs and EGCG in particular are able to activate a pathway for cell differentiation in normal human epidermal keritinocytes (NHEKs). In contrast to tumor cells, NHEKs undergo accelerated differentiation when exposed to EGCG, which is associated with induction of p57/KIP2, a cyclin-dependent kinase inhibitor involved in cell growth and differentiation [1,15]. 

Sirolimus binds to an intracellular receptor protein and elevates p27 levels, which leads to inhibition of cyclin-dependent kinase (CDK) complexes, and ultimately induces cell-cycle arrest in the late GI phase. It inhibits proliferation of both rat and human SMCs in vitro and reduces intimal thickening in models of vascular injury (29,30). Sirolimus inhibits... 

Atienza C, Jr., Elliott MJ, Dong YB, et al. Adenovirus-mediated E2F-1 gene transfer induces an apoptotic response in human gastric carcinoma cells that is enhanced by cyclin dependent kinase inhibitors. IntJ Mol Med 2000 6(l) 55-63. 

Using 2D-PAGE, cell cycle entry has been shown to be associated with a significant increase in p27(kipl) phosphorylation in human primary B lymphocytes. Detailed analysis revealed that different cyclins and cyclin-dependent kinases interact with distinct posttranslationally modified isoforms of p27(kipl) in vivo. These results have to be interpretated in the context of overexpression of cyclin D3 in the presence of high levels of p27(kipl) in human B-cell lymphomas with adverse clinical outcome [110]. 

Z5. Zhuang, S. H., and Burnstein, K. L., Antiproliferative effect of la,25-dihidroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation. Endocrinology 139, 1197-1207 (1998). 

Achenbach TV, Slater EP, Brummerhop H, Bach T, Muller R (2000) Inhibition of cyclin-dependent kinase activity and induction of apoptosis by preussin in human tumour cells. Antimicrobiol Agents Chemother 44 2794-2801... 

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