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Cell Cycle Regulation Cell Cycle analogy to washer machine control The cell cycle is driven by an internal clock regulated at certain checkpoints by both external (ex: faucets) and internal (ex: sensor) controls. Major Checkpoints of the Cell Cycle Control System Cell Cycle Clock: Cyclins and CyclinDependent Kinases Cyclin fluctuates cyclically within the cell. Cyclin–dependent kinases (Cdks) such as MPF must be attached to cyclin to be active (MPF = mitosis promoting factor) Activity of Cdks rise and fall with changes in cyclin concentration. MPF complex initiates mitosis by phosphorylating a variety of proteins. MPF switches itself off by initiating a process that breaks down cyclin. The effect of a Growth Factor on Cell Division PDGF = plateletderived growth factor A growth factor is a protein released by certain body cells that stimulates other cells to divide. Density-Dependent Inhibition • Crowded cells stop dividing. • Cultured cells normally divide until they form a monolayer. • If some cells are removed, cell division begins in cells bordering the gap until it is filled. • Most animal cells also exhibit anchorage dependence Cancer cells have escaped from cell cycle controls Cancer cells: • do not exhibit density-dependent inhibition or anchorage dependence. • do not stop dividing when growth factors are depleted. • can go on dividing indefinitely in culture if given a continual supply of nutrients (immortal). • transformation is the process that converts a normal cell to a cancer cell.