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Cell cycles/kinases

Blagden S, de Bono J (2005) Drugging cell cycle kinases in cancer therapy. Curr Drug Targets 6 325-335... [Pg.345]

Longshaw, V.M. et al. (2004) Nuclear translocation of the Hsp70/Hsp90 organizing protein mSTIl is regulated by cell cycle kinases./. Cell Sci. 117, 701-710. [Pg.1089]

As might be expected from other mechanisms of regulation described in this text, phosphorylation and dephosphorylation of key proteins is the main mechanism for regulating the cycle, i.e. reversible phosphorylation, also known as interconversion cycles (discussed in Chapter 3). In the cell cycle, several of these interconversion cycles play a role in control at the checkpoints. Two important terms must be appreciated to help understand the mechanism of regulation of the cycle the phosphorylation of proteins is catalysed by specific protein kinases, known as cell-division kinases (cdck) or cell cycle kinases (cck) and these enzymes are activated by specific proteins, known as cyclins. [Pg.474]

Figure 20.31 The principle of interconversion cycles in regulation of protein activity or changes in protein concentration as exemplified by translation/proteolysis or protein kinase/protein phosphatase. They result in very marked relative changes in regulator concentration or enzyme activity. The significance of the relative changes (or sensitivity in regulation) is discussed in Chapter 3. The principle of regulation by covalent modihcation is also described in Chapter 3. The modifications in cyclin concentration are achieved via translation and proteolysis, which, in effect, is an interconversion cycle. For the enzyme, they are achieved via phosphorylation and dephosphorylation reactions. In both cases, the relative change in concentration/activity by the covalent modification is enormous. This ensures, for example, that a sufficient increase in cyclin can occur so that an inactive cell cycle kinase can be converted to an active cell cycle kinase, or that a cell cycle kinase can be completely inactivated. Appreciation of the common principles in biochemistry helps in the understanding of what otherwise can appear to be complex phenomena. Figure 20.31 The principle of interconversion cycles in regulation of protein activity or changes in protein concentration as exemplified by translation/proteolysis or protein kinase/protein phosphatase. They result in very marked relative changes in regulator concentration or enzyme activity. The significance of the relative changes (or sensitivity in regulation) is discussed in Chapter 3. The principle of regulation by covalent modihcation is also described in Chapter 3. The modifications in cyclin concentration are achieved via translation and proteolysis, which, in effect, is an interconversion cycle. For the enzyme, they are achieved via phosphorylation and dephosphorylation reactions. In both cases, the relative change in concentration/activity by the covalent modification is enormous. This ensures, for example, that a sufficient increase in cyclin can occur so that an inactive cell cycle kinase can be converted to an active cell cycle kinase, or that a cell cycle kinase can be completely inactivated. Appreciation of the common principles in biochemistry helps in the understanding of what otherwise can appear to be complex phenomena.
Mechanism of regulation of cell cycle kinases and activation of checkpoints... [Pg.475]

Figure 20.32 A hypothesis for regulation of cydin-dependent cell cycle kinase by changes in the concentration of a cyclin and how... Figure 20.32 A hypothesis for regulation of cydin-dependent cell cycle kinase by changes in the concentration of a cyclin and how...
The active cyclin-dependent cell cycle kinase is dephosphorylated by a protein phosphatase which inactivates the enzyme. [Pg.476]

The Rb protein binds to the transcription factor, forming a complex in which the factor is inactive. However, when the Rb protein is phosphorylated by a cell cycle kinase, the complex dissociates, so that the transcription factor is released and is then available to activate the three genes allowing cell proliferation to occur (Figures 21.16 21.17). Mutations in the Rb gene that resnlt in the synthesis of a protein with a reduced capacity to bind the transcription factor, resnlts in uncontrolled cell proliferation. [Pg.495]

Figure 21.17 Overview of the regulation of the genes that express three proteins essential for DNA synthesis. The Rb gene expresses Rb which inactivates the transcription factor by forming a complex. Phosphorylation of the Rb protein by a cell cycle kinase causes dissociation of complex and release of transcription factor, which is now active and stimulates expression of the three genes. THFR, tetra hydrofolate reductase. See chapter 20 for details of the actions of cyclins, DNA polymerase and THFR in the cell cycle. Figure 21.17 Overview of the regulation of the genes that express three proteins essential for DNA synthesis. The Rb gene expresses Rb which inactivates the transcription factor by forming a complex. Phosphorylation of the Rb protein by a cell cycle kinase causes dissociation of complex and release of transcription factor, which is now active and stimulates expression of the three genes. THFR, tetra hydrofolate reductase. See chapter 20 for details of the actions of cyclins, DNA polymerase and THFR in the cell cycle.
De Azevedo, W.F. et al.. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase, Proc. Natl Acad. Sci. USA, 93, 2735, 1996. [Pg.466]

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. [Pg.540]

The use of the 6-amino group and N1 nitrogen of the purine base to model the pharmacophore, as seen with staurosporine, is not possible in two other adenine-type inhibitors. Both isopentenyl adenine, a nonspecific inhibitor of protein kinases, and olomoucin, a more specific inhibitor of Ser/Thr protein kinases, are modified only at the 6-amino group position. Thus, bidentate hydrogen-bond formation as seen in the ATP purine base is not possible. Furthermore, there are inhibitors that do not contain the chemical structure of adenine, for example des-chloro-flavopyridol, a potent inhibitor of cdc-2 cell cycle kinase. [Pg.225]

Pyrazolopyridinyl pyrimidines, (V), prepared by Chamberlain (6) and imidazolo-5-yl-2-anilino-pyrimidine derivatives, (VI), prepared by Breault (8) were effective as CDK2, CDK4 and CDK6 cell cycle kinase inhibitors. [Pg.554]

Pol II is not the only target of Cdks. Cell-cycle kinases also control transcription by phosphorylation of TBPs and TBP-associated factors, TAFs although, at least in yeast, TAFs seem not to be obligatory for transcription. Tumour suppressors, such as p53, which are controlled by phosphorylation by Cdks, link transcription and the cell cyde. i Breakdown of transcriptional control by tumour suppressors is related to cancer. This is discussed in Part 4. [Pg.161]

Doree, M., and T. Hunt. 2002. From Cdc2 to Cdkl when did the cell cycle kinase join its cyclin partner J. Cell Sci. 115 ... [Pg.896]

Cell cycle arrest and the induction of apoptosis could be functionally related to the activation of p53 and/or the inhibition of cell cycle kinase activity, and research results suggest that flavonoids may be more effective in controlling the growth of tumours with certain mutational spectra [118],... [Pg.1198]

Promotes growth arrest at G2/M induction of GADD45 phosphorylation and inactivation of the cell-cycle kinase, cdc2 Promotes DNA human... [Pg.379]

Due to the overexpression of cyclins and Cdks, cell cycle kinase activity is frequently upregulated in human cancers this may occur because of Cdk inhibitor inactivation. Deregulation of the cyclin Dl-Rb... [Pg.68]


See other pages where Cell cycles/kinases is mentioned: [Pg.565]    [Pg.360]    [Pg.475]    [Pg.475]    [Pg.476]    [Pg.477]    [Pg.208]    [Pg.281]    [Pg.294]    [Pg.203]    [Pg.519]    [Pg.368]    [Pg.177]    [Pg.108]    [Pg.169]    [Pg.213]   


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Cell cycle cyclin-dependent kinase inhibitors

Cell cycle kinases, regulation

Cyclin-dependent kinase cell cycle regulation

Cyclin-dependent kinase inhibitors cell cycle regulation

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