Cells can chose to commit suicide or recover when “sick” and a protein called DR5 has been shown to be important in this choice. When a cell becomes sick, such as when it is invaded by a virus or has become a cancer cell, it can chose to commit suicide. There are specific genes that switch on when the cell decides to commit suicide and these genes have been called suicide genes. If the suicide gene is activated, the cell will die.
In the study recently reported in Science, researchers from the University of California in San Francisco looked at the molecular mechanisms of apopotosis, which is the scientific term for cell suicide. They studied protein folding in the endoplasmic reticulum, which is a structure inside the cell that produces lipid and combination lipid-protein molecules. The disruption of protein folding causes endoplasmic reticulum stress. If endoplasmic stress continues for a long time, then the cell will undergo apoptosis, which means it will commit suicide. What was shown in this study was persistent endoplasmic reticulum stress causes a build up of the protein called DR5. The study showed that the protein DR5 integrates signals that oppose protein folding and apoptosis, thereby sealing the cell’s fate of death.
Another aspect to these cellular events is a cellular stress pathway, called the unfolded-protein-response, which can either activate or degrade the DR5 protein. The unfolded-protein-response can therefore either promote or prevent cell suicide. It seems that the initial endoplasmic reticulum stress will block cell suicide so that the cell can recover, or else, if the stress persists, the activity in the same pathway will trigger apoptosis. Simply put, if protein folding in the endoplasmic reticulum goes awry and unfolded proteins build up, then the endoplasmic reticulum will become stressed, and the cell will carry out apoptosis.
On a cellular level, Type 1 diabetes may be a case where problems in the unfolded-protein-response cause a loss of pancreatic cells that produce insulin. The disruption of the unfolded-protein-response pathway could cause stress in the endoplasmic reticulum, which could result in apoptosis of these important pancreatic cells. Understanding the role of DR5 in apoptosis might be helpful in developing a better understanding of what is happening in Type 1 diabetes on a cellular level.
A better understanding of the cellular mechanisms of cancer may results from this research as well. One of the ways that a cell can become a cancer cell is for the suicide gene to become mutated. When cells become changed and are turned into a cancer cell, the suicide gene is supposed to “turn on” and make the cell commit suicide. However, if that gene is mutated it cannot produce the protein needed for cell suicide and then the cell will not die. It will continue to live and reproduce, making even more cancer cells, resulting in a cancerous tumor.
The study was described as making the most beautiful simplification of all this big complex mess by Alexei Korennykh, who is a professor of molecular biology at Princeton University. However, there are still questions about whether activity in the unfolded-protein-response pathway is the sole cause of a cell’s deciding to commit suicide or whether there are other pathways that might be involved. It is likely that there are different situations for different types of cells. Discovering that the DR5 protein is important in determining whether a cell will commit suicide or recover is certainly a good step in the right direction.
By Margaret Lutze