Researchers found mechanism behind the cell stress response of misfolded proteins

So far, no one has completely how cells regulate an appropriate response to the build-up of misfolded proteins. Once cells are under stress, proteins misfold. What's worse, when these misfolded proteins are not properly handled, they can build-up in the cell, resulting in death and disease. To optimize function, cells should maintain the right balance of fixing and clearing out misfolded proteins without taxing the system by responding when the number of damaged proteins is low. New research from the Cornell University was published online on Nov. 9 in Nature Cell Biologyhttp://www.cusabio.com/. It shows a system that controls levels of a cell’s sensors, which is called IRE1α, is responsible for sensing the accumulation of misfolded proteins. IRE1α is found in almost every cell type which trigger the action of a complex named the endoplasmic reticulum-associated degradation (ERAD), thus fixing or degrading misfolded proteins before they accumulate. During the research, the researchers found that the ERAD complex actually controls the level of the IRE1α sensor, so it doesn't trigger a major response during normal or low levels of cell stress and protein misfolding. The ERAD complex has the ability of recognizing the sensor and putting it in the trash when there is low level of activation or in basal conditions. The cells need right response because too much of an IRE1α response can lead to cell death. They also found that once in the high levels of cellular stress, when misfolded proteins are accumulating, an intermediary protein called BiP uncouples the IRE1α sensor from ERAD's control. Subsequently, the IRE1α sensor can accumulate and give a response to call the ERAD complex to clear out misfolded proteins, which is just like a process of putting out a fire. The researchers took mice to conduct the research. They disabled the ERAD complex in gut lining cells in mice and discovered that the mice developed colitis with an overt activation of the sensor IRE1α. If the sensor protein level is too high, an unwanted alarm will be triggered. This mechanism seems to be critical in gut lining in the development of colitis, according to the research. More research such as how ERAD recognizes and trashes the IRE1α sensor and other proteins and how the mechanism relates to colitis will be focused on in the near future. More treatment will be developed as a result of this new-found mechanism. You can find more here:http://www.cusabio.com/ELISA-Kit/Human-Interleukin-18IL-18-ELISA-KIT-11090105.html