CDKs

Jeffrey, P.D., et al. Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature 376 31.3-320, 1995. 

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. 

The rationale behind CDK inhibition during anticancer treatment is to stop hyperactive cell cycles and to inhibit the activity of cyclins that are frequently overexpressed in human cancer. 

Sherr CJ, Roberts JM (1999) CDK inhibitors positive and negative regulators of G1-phase progression. Genes Dev 13 1501-1512... 

Growth inhibition by TGF- 3, associated with inhibition of c-myc, cdks, reduction in cyclin D1 levels, and inhibition of cdk-4-associated Rb kinase activity, as well as induction of cdk inhibitors pi5 and p27, has been noted in intestinal epithelial cells. Loss of responsiveness to growth inhibition from TGF- 3 occurs in many cell types including breast, colorectal carcinoma, and pancreatic carcinoma cells. Mutational inactivation of T 3RH represents one mechanism of this process, which in many cases, leads to the development of gastrointestinal cancer. Thirteen percent of colorectal carcinomas are thought to be associated with a replication error (RER) or microsatellite instability phenotype. Subsequent inactivation of T 3RII and... 

Opcn-ciitnit actks am strength of adsorption Weak adsorption Raft DuSit.i e order in i > v. cdk adsorption Rate positive order in A 5r/f pA>()... 

Chemistry Java library for chemoinformatics and http //almost.cubic.uni-koeln.de/cdk/... 

Othet cyclins and CDKs are involved in different aspects of cell cycle progression (Table 36-7). Cychn E and CDK2 form a complex in late Gl. Cychn E is tapidly degraded, and the released CDK2 then fotms a complex with cyclin A. This sequence is necessaty fot the initiation of DNA synthesis in S phase. A complex between cychn B and CDKl is tate-hmiting fot the G2/M transition in eukatyotic cells. 

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