Chapter 4 • Most cells in postnatal tissues are quiescent. Exceptions include abundant cells of the hematopoietic system, skin, and gastrointestinal mucosa, as well as other minor progenitor populations in other tissues. • Many quiescent cells can reenter into the cell cycle with the appropriate stimuli, and the control of this process is essential for tissue homeostasis. • The key challenges for proliferating cells are to make an accurate copy of the 3 billion bases of DNA (S phase) and to segregate the duplicated chromosomes equally into daughter cells (mitosis). • Progression through the cell cycle is dependent on both intrinsic and extrinsic factors, such as growth factor or cytokine exposure, cell-to-cell contact, and basement membrane attachments. • The internal cell cycle machinery is controlled largely by oscillating levels of cyclin proteins and by modulation of cyclin-dependent kinase (Cdk) activity. One way in which growth factors regulate cell cycle progression is by affecting the levels of the D-type cyclins, Cdk activity, and the function of the retinoblastoma protein. • Cell cycle checkpoints are surveillance mechanisms that link the rate of cell cycle transitions to the timely and accurate completion of prior dependent events. p53 is a checkpoint protein that induces cell cycle arrest, senescence, or death in response to cellular stress. • Checkpoints minimize replication and segregation of damaged DNA or the abnormal segregation of chromosomes to daughter cells, thus protecting cells against genome instability. • Disruption of cell cycle controls is a hallmark of all malignant cells. Frequent tumor-associated alterations include aberrations in growth factor signaling pathways, dysregulation of the core cell cycle machinery, and/or disruption of cell cycle checkpoint controls.
Control of the Cell Cycle
Summary of Key Points
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Control of the Cell Cycle
