Regulation of the Cell Cycle CHAPTER 12

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1 Regulation of the Cell Cycle CHAPTER 12

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6 Regulation of the Cell Cycle Timing and rates of cell division in different parts of an animal or plant are crucial for normal growth, development, and maintenance. Frequency of cell division varies with cell type Skin cells divide frequently throughout life Liver cells retain the ability to divide but only do so under specific conditions. Mature nerve and muscle cells do not appear to divide at all after maturity Sequential event of the cell cycle are directed by a distinct cell cycle control system Internal control system may also be influenced by external factors

7 Checkpoints in Cell Cycle Control A checkpoint is a critical control point where stop and/or go-ahead signals regulate the cycle Checkpoint signals are transmitted within the cell by signal transduction pathways Animal cells generally have built-in stop signals that must be overridden in order for the cycle to continue. Many of the signals are based on the completion of some necessary cellular process. Checkpoints also register signals from outside the cell Three major checkpoints G1, G2, and M phases

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9 The clock has specific checkpoints Where the cell cycle stops until a go-ahead signal is received G 0 G 1 checkpoint G 1 G 1 Figure A, B (a) If a cell receives a go-ahead signal at the G 1 checkpoint, the cell continues on in the cell cycle. (b) If a cell does not receive a go-ahead signal at the G 1 checkpoint, the cell exits the cell cycle and goes into G 0, a nondividing state.

10 G1 checkpoint If a cell receives the go-ahead at G1 it will usually complete the cell cycle If it does not receive a go-ahead signal, the cell exits the cycle and switches to a nondividing state, the G 0 phase. Most cells in the human body are in this phase Liver cell can be called back to the cell cycle by external cues, such as growth factors released during injury.

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16 (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle M G 1 S G 2 M G 1 S G 2 MPF activity Cyclin M Time (b) Molecular mechanisms that help regulate the cell cycle 5 During G 1, conditions in the cell favor degradation of cyclin, and the Cdk component of MPF is recycled. Degraded Cyclin Cdk Cyclin is degraded G 2 checkpoint MPF Cdk Cyclin 1 2 Synthesis of cyclin begins in late S phase and continues through G 2. Because cyclin is protected from degradation during this stage, it accumulates. Accumulated cyclin molecules combine with recycled Cdk molecules, producing enough molecules of MPF to pass the G 2 checkpoint and initiate the events of mitosis. Figure A, B 4 During anaphase, the cyclin component of MPF is degraded, terminating the M phase. The cell enters the G 1 phase. 3 MPF promotes mitosis by phosphorylating various proteins. MPF s activity peaks during metaphase.

17 External Chemical & Physical Growth factors = proteins released by one group of cells that stimulate other cells to divide. About 50 different growth factors trigger specific cells to divide Density-dependent inhibition In lab cultures, cells normally divide until they form a single layer on the inner surface of the culture container. If a gap is created, the cells will grow to fill it in Anchorage dependence In order to divide, cells must be anchored to a substratum

18 Growth factors Stimulate other cells to divide EXPERIMENT Scalpels 1 2 A sample of connective tissue was cut up into small pieces. Enzymes were used to digest the extracellular matrix, resulting in a suspension of free fibroblast cells. Petri plate Figure Cells were transferred to sterile culture vessels containing a basic growth medium consisting of glucose, amino acids, salts, and antibiotics (as a precaution against bacterial growth). PDGF was added to half the vessels. The culture vessels were incubated at 37 C. With PDGF Without PDGF

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23 Cancer cells have escaped from cell cycle controls Cancer cells divide excessively and invade other tissues because they are free of the body s control mechanisms. do not stop dividing when growth factors are depleted. may manufacture their own growth factors or they have an abnormality in signaling pathway When cancer cells stop dividing, they do so at random points, not at the checkpoints.

24 Cancer cells (continued) Cells undergo transformation conversion from normal to cancer cell Normally, the immune system recognizes and destroys transformed cells If immune system misses some cells they may proliferate to form tumors Benign tumors abnormal cells remain at original site Malignant tumor cells become invasive enough to impair the functions of one or more organs

25 Malignant Tumors Cancer cells may lose attachment and metastasize Cancer cells are abnormal in many ways Unusual number of chromosomes Abnormal metabolism May secrete signal molecules that cause blood vessels to grow toward the tumor.