Gourt Home::Gourt :: Heat shock protein
Heat shock proteins (HSP) are a group of proteins whose expression is increased when the cells are exposed to elevated temperatures. This increase in expression is transcriptionally regulated. This dramatic upregulation of the heat shock proteins induced mostly by Heat Shock Factor (HSF) is a key part of the heat shock response. Production of high levels of heat shock proteins can also be triggered by exposure to different kinds of environmental stress conditions, such as infection, inflammation, exposure of the cell to toxins (ethanol, arsenic, trace metals and ultraviolet light, among many others), starvation, hypoxia (oxygen deprivation), nitrogen deficiency (in plants), or water deprivation. Consequently, the heat shock proteins are also referred to as stress proteins and their upregulation is sometimes described more generally as part of the stress response.
Scientists have not discovered exactly how heat-shock (or other environmental stressors) activates the heat-shock factor. However, some studies suggest that an increase in damaged or abnormal proteins brings HSPs into action.
Heat-shock proteins are present in all cells at all biological levels. They appear when the cell is under heat stress (or other stress). Heat-shock proteins also occur under non-stressful conditions, simply "monitoring" the cell's proteins. Some examples of their role as "monitors" are that they carry old proteins to the cell's "recycling bin" and they help newly synthesised proteins fold properly. These activities are part of a cell's own repair system, called the "cellular stress response" or the "heat-shock response." The function of heat-shock proteins is similar in virtually all living organisms, from bacteria to humans.
Heat shock proteins are molecular chaperones for protein molecules. They are usually cytoplasmic proteins and they perform functions in various intra-cellular processes. They play an important role in protein-protein interactions such as folding and assisting in the establishment of proper protein conformation (shape) and prevention of unwanted protein aggregation. By helping to stabilize partially unfolded proteins, HSPs aid in transporting proteins across membranes within the cell. Some members of the HSP family are expressed at low to moderate levels in all organisms because of their essential role in protein maintenance.
The HSPs are named according to their molecular weights, for example Hsp70 and Hsp90 each define families of chaperones. The major classes of heat shock proteins are tabulated below.
Potential applications
Heat-shock proteins are of potential interest to cancer researchers, based on research that has shown that animals may respond to cancer "vaccinations." Tumor cells were "attenuated" (or weakened) and injected in small quantities into a rodent, causing the rodent to become immune to future full-fledged tumor-cell injections. While any relevance of animal research to humans has not been established, it is possible that the same may hold true for other species.
Some researchers are conducting research on using heat shock proteins in the treatment of cancer. Some researchers speculate that HSPs may be involved in binding protein fragments from dead malignant cells and presenting them to the immune system.
Researchers are also investigating the role of HSPs in conferring stress tolerance to hybridized plants, hoping to address drought and poor soil conditions for farming.
Researchers
Many years after the tumor cell attenuation research was done, Pramod Srivastava discovered that the specific part of the cell that was protecting the "immune" mice was the heat-shock proteins.
Susan Lindquist is currently a leading heat-shock protein researcher. She is investigating, among other things, "how HSPs are regulated, and how they function to protect organisms from death and from developmental anomalies induced by heat." - from her faculty page at: http://web.wi.mit.edu/lindquist/pub/. A list of heat shock protein researchers can be found at http://www.heatshock.net/labs.php
Chaperones and heat shock proteins
The principal heat-shock proteins that have chaperone activity belong to five conserved classes: HSP100, HSP90, HSP70, HSP60 and the small heat-shock proteins (sHSPs).
| Approximate molecular weight | (kDa)Prokaryotic proteins | Eukaryotic proteins | Function |
|---|---|---|---|
| 10 kDa | GroES | Hsp10 | |
| 20-30 kDa | GrpE | The HspB group of Hsp. Ten members in mammals including Hsp27 or HspB1 | |
| 40 kDa | DnaJ | Hsp40 | |
| 60 kDa | GroEL, 60kDa antigen | Hsp60 | |
| 70 kDa | DnaK | The HspA group of Hsp including Hsp71, Hsc70, Hsp72, Grp78, BiP, Hsx70 found only in primates | Protein folding and unfolding, provides thermotolerance to cell on exposure to heat stress |
| 90 kDa | HtpG, C62.5 | The HspC group of Hsp including Hsp90, Grp94 | Maintenance of steroid receptors and transcription factors |
| 100 kDa | ClpB, ClpA, ClpX | Hsp104, Hsp110 | Tolerance of extreme temperature |
Although the most important members of each family are tabulated here, it should be noted that some species may express additional chaperones, co-chaperones, and heat shock proteins not listed. Additionally, many of these proteins may have multiple splice variants (Hsp90α and Hsp90β, for instance) or conflicts of nomenclature (Hsp72 is sometimes called Hsp70).
See also
"Heat shock protein"