The cell cycle is tightly regulated by genetic signals and external signals.
Cell growth, cell division, and even cell death are normal processes that happen regularly. In multicellular organisms, the cell cycle and cell division happen at different rates, depending on the type of cell. For example, human skin cells divide regularly throughout a person's life, whereas cells in the human heart divide only rarely, if at all. Regulation of cell division is thus of great importance to each cell and to the whole organism. Mechanisms of this regulation have been studied thoroughly, both to better understand the normal cell cycle and also to gain insight into cancer, which happens when cell regulation ceases to function properly.
The Cell-Cycle-Control System
The cell-cycle-control system regulates cell growth and division by a series of checkpoints that are controlled by the interaction of cyclin-dependent kinases and cyclins.
The regulation of the cell cycle is maintained by the cell-cycle-control system, a series of checkpoints directed by chemical signals in the cell that regulate growth and division. These checkpoints occur at different points in the cell cycle—near the end of the G1 phase, at the end of G2 phase, and during the M phase. The gatekeepers of these checkpoints are regulatory molecules categorized into two types: cyclins and cyclin-dependent kinases. A cyclin-dependent kinase (Cdk) and a cyclin are regulatory molecules (usually proteins) that work together as gatekeepers, along to move a cell past checkpoints in the cell cycle. In general, Cdks are present in constant concentration in a cell, regardless of which phase the cell is in. Most of the time Cdks are inactive. Cdks are tied to a specific cyclin, and the activity of Cdks is thus tied to the concentration of the cyclin partner. For example, the Cdk Maturation-promoting factor (MPF) triggers the cell to enter the M phase when activated by its cyclin partner. Although MPF is present in a cell all the time, its activity is closely tied to the concentration of its cyclin.
MPF (maturation-promoting factor) activity, which triggers the cell to enter the M phase, is tied to the relative concentration of its cyclin, regulatory proteins that vary in concentration levels.
In general, the cellular proteins involved in moving from one phase of the cell cycle to another are maintained in an inactive state by signals produced inside and outside the cell. These signals take many forms, including proteins and hormones. When internal and external signals cause the production of cyclins at high levels, they activate the Cdks. In turn, the Cdks activate cellular proteins that trigger the cell to move to the next phase of the cell cycle. This default inactive state provides the cell protection against unchecked growth and division. For example, muscle cells in the human heart never receive the signal to proceed through the G1 checkpoint to enter the division steps of the cell cycle. These cells exit the cell cycle and remain at rest for the duration of their lives. If the cell dies, it is replaced by cells coming from undifferentiated cells still in the cell cycle, rather than from adjacent heart muscle cells. However, it is now known that some cells which have left the cell cycle can reenter it based on external signals, such as growth factors. This may happen in response to injury or other trauma. These signals override the default inactive states of the checkpoints and draw the cell back into the cell cycle.
Cancer: Unregulated Cellular Division
Cancer is uncontrolled cell growth and division.
Maintaining control of cell division is important in order to preserve the structural integrity of tissues and organs, and therefore the function of these structures. However, mutations in the DNA can result in cells not heeding signals that tell them to stop dividing. This results in unregulated cell growth and division called cancer. These mutations can result from errors during DNA replication, exposure to chemicals that cause changes in the DNA, or exposure to some viruses that cause DNA mutations. There are many types of cancer, and thus many ways for the cell-cycle-control system to fail. Some cells simply do not stop at the established checkpoints. For example, they may pass from G1 to S or G2 to M without going through the usual proofreading. Others stop at random points in the cell cycle or interact in unusual ways with cyclins and Cdks. Many types of cancer cells will continue dividing as long as they continue to receive nutrients. The first human cells ever grown in a laboratory came from a cancerous tumor extracted from a woman named Henrietta Lacks. These cells were placed in a glass dish in 1951, and the descendants of those cells are still grown in labs today. In contrast, normal cells placed in a glass dish will only divide about 50 times before they exit the cell cycle.
