Regulation of the Cell Cycle
► Different types of cells divide at different rates. Skin cells divide frequently, whereas liver cells divide only in response to injury and nerve, muscle, and other specialized cells do not divide in mature humans.
- The cell cycle control system consists of a molecular clock and a set of checkpoints that ensure that appropriate conditions have been met before the cycle advances.
- For instance, cells must be in contact with adjacent cells before proper division can occur.
Also, cells must reach a certain size and volume before they can properly divide. All of the DNA must be properly replicated before the cell divides.
- Checkpoints are present in the G1, G2, and M phases of the cell cycle. The G1 checkpoint is the most critical one for many cells.
- If the proper signals are not received, the cell may stay in a stage known as G0; or the nondividing state.
- Protein Kinases are enzymes that help synchronize the cell cycle events. Protein Kinases catalyze the transfer of a phosphate group from ATP to a target protein.
- Phosphorylation induces a conformational change that either activates or inactivates a target protein.
- Changes in these target proteins affect the progression through the cell cycle.
- Cyclical changes in kinase activity, in turn, are controlled by proteins called Cyclins.
- Protein kinases that regulate cell cycles are active only when attached to a particular Cyclin molecule.
- Cyclin concentrations, in turn, vary throughout the cell cycle (they are highest as the cells prepare to divide). By the end of cytokinesis, cyclins are present in much smaller concentrations. The cyclins are broken down as the cells progress through the M-phase of cell division.
- Cyclins bind with protein kinases early in the cell cycle and produce Mitosis Promoting Factor (MPF). MPF promotes chromosome condensation and nuclear membrane absorption.
- Later in the cell cycle, MPF activates proteolytic enzymes (these enzymes break down proteins) which destroy the cyclin.
- Thus, new Cyclin proteins must be produced during interphase, until appropriate levels build up and promote cell division.
► Certain Chemicals called Growth Factors have been isolated and are known to promote cell division as they bind to receptors of the plasma membrane. Platelet Derived Growth Factor is an example of one type of chemical signal. It may help cells to divide to heal wounds.
► If cells are too crowded, they will not divide under ordinary circumstances. Sufficient quantities of nutrients and growth factors may be lacking. Also, most cells must be adhered to an extracellular matrix in order to divide.
► Membrane proteins and cytoskeletal elements provide signals which indicate that proper anchorages exist.