34.4: Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Proteins, such as cyclin and cyclin-dependent kinases, are positive regulator molecules responsible for the cell cycle’s progression through various checkpoints. The cyclins were initially named such because their synthesis and degradation assume a cyclical pattern. There are at least four functional cyclins whose concentration fluctuates predictably across the cell cycle. When a cell gets promoted to the next stage, the cyclins of the previous phase get degraded. It is the changes in the cyclin concentration that trigger various cell cycle events.
Cyclins form an active complex with protein kinases that can phosphorylate specific target proteins during the cell cycle. Because these kinases need cyclin for activation, they are called cyclin-dependent kinases or Cdks. In the absence of cyclin, the Cdks are inactive, and in the absence of a fully activated cyclin/Cdk complex, the cell fails to pass through the checkpoints.
The positive regulator molecules are expressed by genes that belong to a group called proto-oncogenes. When mutated, these become oncogenes that cause the cell to become cancerous. For instance, a mutation that causes the Cdks to become active even in the absence of cyclin can cause the mutant cell to pass uninterrupted through the checkpoints leading to uncontrolled growth and proliferation.