When a cell is exposed to increased temperatures or other stresses, heat shock protein expression increases through enhancement of transcription. This is known as the heat shock response and is thought to be caused by heat shock factor. Heat shock proteins are named based upon their molecular weight. For example, the commonly studied Hsp60, Hsp70 and Hsp90 refer to heat shock proteins of size 60, 70, and 90 kilodaltons.
The discovery of heat shock proteins stemmed from the observation that brief exposure of cells to high temperature can provide protection from subsequent larger increases in temperature, even at temperature which are normally lethal. Heat shock proteins were first demonstrated in Drosophila. The increase in transcription following cell stress was first reported in 1974. A decade later, scientists discovered the role of heat shock proteins as molecular chaperones, directing protein folding and assisting in protein trafficking.
Function
Besides heat, other stressors such as infection, inflammation, toxins, hypoxia, starvation and even exercise can result in the production of increased levels of heat shock proteins. For this reason, heat shock proteins are also known as stress proteins and they are considered an important part of the cellular stress response. It is thought that an increase in protein damage can trigger this response.
Heat shock proteins are also important in protein folding and ensuring the proper protein conformation. They play an important role in the prevention of protein aggregation. By stabilizing partially unfolded proteins, they help in the transport of proteins across various intracellular membranes. This essential role means that some heat shock proteins are ubiquitous in all cells. Indeed, heat shock proteins are present during non-stressful conditions, playing a housekeeping role. Some of these housekeeping tasks include transporting old proteins to proteasomes for recycling and the assistance of folding of nascent protein chains.
Heat shock proteins also have other roles such as promoting smooth muscle relaxation in the vasculature and the presentation of antigens to the immune system.
Applications
As described above, heat shock proteins are very good at presenting antigens to the immune system. For this reason, they can be used as a vaccine adjuvant to boost the body’s response to a vaccine, including cancer vaccines. Heat shock proteins may also be important in binding protein fragments from dead malignant cells and presenting them to the immune system to further increase the effectiveness of cancer vaccines.
Heat shock proteins are also present in malignant cells and they may be important in tumor survival. Small molecule heat shock protein inhibitors such as the Hsp90 inhibitor, 17-AAG may act as a potent anti-cancer agent.