Heat shock protein

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Heat shock proteins (HSP) are a group of proteins whose expression is increased when the cells are exposed to elevated temperatures or other stress. 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.

The function of heat-shock proteins is similar in virtually all living organisms, from bacteria to humans.

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.

1 Upregulation through stress
2 Monitoring
3 Chaperone function
4 Cancer
5 Agriculture
6 Cardiovascular role
7 Researchers
8 Chaperones and heat shock proteins
9 See also
10 References
11 External links

[edit] Upregulation through stress

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.

[edit] Monitoring

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".

[edit] Chaperone function

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.

[edit] Cancer

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.

[edit] Agriculture

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.

[edit] Cardiovascular role

Heat shock proteins appear to serve a significant cardiovascular role. Hsp90, hsp84, hsp70, hsp27, hsp20, and alpha beta crystalline all have been reported as having roles in the cardiovasculature.

Hsp90 binds both endothelial nitric oxide synthase and soluble guanylate cyclase (also hsp90 serves a significant role in some cancers).

A downstream kinase of the nitric oxide cell signalling pathway, protein kinase G, phosphorylates a small heat shock protein, hsp20. Hsp20 phosphorylation correlates well with smooth muscle relaxation and is one significant phosphoprotein envolved in the process. Hsp 20 appears significant in development of the smooth muscle phenotype during development. Hsp 20 also serves a significant role in preventing platelet aggregation, cardiac myocyte function and prevention of apoptosis after ischemic injury, and skeletal muscle function and muscle insulin response.

Hsp 27 is a major phosphoprotein during all muscle contraction. Hsp 27 functions in smooth muscle migration and appears to serve an integral role in actin filament dynamics and focal adhesions.

It is hypothesized that hsp27 and hsp20 may serve some role in cross-bridge formation between actin and myosin.

[edit] 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".^[1]

[edit] Chaperones and heat shock proteins

The principal heat-shock proteins that have chaperone activity belong to five conserved classes: HSP100, HSP90, HSP70, HSP60, HSP33, 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	Involved in protein folding after its post-translational import to the mitochondrion/chloroplast
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. Also prevents protein folding during post-translational import into the mitochondrial/chloroplast.
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).