Cell cycle overview

Table 10.10 Overview of some of the effects of the IGFs Promotes cell cycle progression in most cell types...

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.

In summary, due fo fhe large panel of cell cycle regulatory proteins regulated by HDACs at the level of either their expression or activity, the antiproliferative effect of HDAC inhibitors cannot be linked to a single mechanism of action. The relative importance of the different proteins affected by HDACs varies between tumors. In Fig. 2, a visual overview of the role of HDACs in various hallmark processes in the development of cancer is shown. 

Medina PP, Slack FJ (2008) microRNAs and cancer an overview. Cell Cycle 7 2485-2492... 

Figure 1 Overview of the different phases of the cell cycle. Quiescent cells are in GO phase and reenter the cell cycle at Gl during which cells prepare for DNA synthesis. After passing the restriction point in late Gl cells are committed to enter S phase, during which DNA replication occurs. Cells in G2 phase prepare for mitosis (M phase). Cell cycle progression is controlled by various positive and negative cell cycle regulatory proteins including cyclins (A, B, D, E) cyclin dependent kinases (cdk 1,2, 4, 6) cdk inhibitors (p15, p16, p18, p19, p21, p27, p57), retinoblastoma (Rb) and p53.

Bodwell, J.E., J.C. Webster, C.M. Jewell, J.A. Cidlowski, J.M. Hu and A. Munck. Glucocorticoid receptor phosphorylation overview, function and cell cycle-dependence. J. Steroid Biochem. Mol. Biol. 65 91 -99, 1998. 

Because of the problems in identifying cellular substrates of protein kinases, as described in Chapter 7, it has been a difficult and lengthy process to determine the functionally relevant substrates. Figure 13.11 gives an overview of the cell-cycle-specific activation of CDKs and some important substrates. Comparatively sparse information is available on the Gr and S-phase substrates of the CDKs. In contrast, many proteins have been described that undergo specific phosphorylation in G2/M phase. The sequence (K/R)-S/T-P-X-K (X any amino acid) has been identified as a consensus sequence for phosphorylation by CDKs. 

Fig. 13.11 Su bstrates and phase-specific activation of CDKs in the cell cycle. An overview is shown of the phase-specific activation of the most important CDK-cyclin complexes and of selected substrates. The arrows indicate activation and phosphorylation.

A FIGURE 21-2 Overview of current model for regulation of the eukaryotic cell cycle. Passage through the cycle is controlled by G-i, S-phase, and mitotic cyclin-dependent kinase complexes (green). These are composed of a regulatory cyclin subunit and a catalytic cyclin-dependent kinase (CDK) subunit. 

The complexity of microtubule behavior and the difficulty in determining exactly how occurs the interference of Vinca alkaloids with that complexity has made it very difficult to characterize the precise anticancer mechanism of action of these drugs, which is still not fully understood. A thorough and clear review on what is known about microtubule behavior and the way Vinca alkaloids interact with microtubules and the cell cycle has been published very recently by Mary Ann Jordan [172]. Here, a more general overview will be presented, trying to highlight adequately the main points of this difficult subject. 

Overview - Regulatory proteins such as cyclins (see here), which are essential in certain parts of the cell cycle and deleterious in others, must be eliminated at some point. Proteins that have become damaged must also be removed. 

The cell cycle of somatic cells and mES cells differs markedly both in length and cell cycle phase distribution. The mES cells are characterised by a short cell cycle of 11 to 16 hours (Orford and Scadden, 2008). Cell cycle distribution analysis showed that 10%, 75% and 15% of mES cells are resjjectively in Gl, S and G2/M phase, indicating a very brief G1 phase ( 1.5h) compared to somatic cells ( 10h) (Savatier et al. 1996 Chuykin et al. 2008). In contrast, embryonic fibroblasts show a cell cycle distribution of 70%, 25%, and 5% of cells in Gl, S and G2/M phase, respectively. In this section an overview and comparison of the cell cycle control pathways that are at play in mES cells and somatic cells is given. 

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