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Heat shock protein

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 HSPs are named according to their molecular weights. For example, Hsp60, Hsp70 and Hsp90 (the most widely-studied HSPs) refer to families of heat shock proteins on the order of 60, 70 and 90 kilodaltons in size, respectively. The small 8 kilodalton protein ubiquitin, which marks proteins for degradation, also has features of a heat shock protein[1].

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



It is known that rapid heat hardening can be elicited by a brief exposure of cells to sub-lethal high temperature, which in turn provides protection from subsequent and more severe temperature. In 1962, Ritossa reported that heat and the metabolic inhibitor dinitrophenol induced a characteristic pattern of puffing in the chromosomes of Drosophila. This discovery eventually led to the identification of the heat-shock proteins (HSP) or stress proteins whose expression these puffs represented. Increased synthesis of selected proteins in Drosophila cells following stresses such as heat shock was first reported in 1974[1].

Beginning in the mid-1980's, investigators recognized that many HSPs function as molecular chaperones and thus play a critical role in protein folding, intracellular trafficking of proteins, and coping with proteins denatured by heat and other stresses. Accordingly, the study of stress proteins has undergone explosive growth.

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.


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".

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.


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.[2] Some researchers speculate that HSPs may be involved in binding protein fragments from dead malignant cells and presenting them to the immune system.

Recently it was discovered that Heat Shock Factor 1 (HSF1)is a powerful multifaceted modifier of carcinogenesis. HSF1 knockout mice show significantly decreased incidence of skin tumor after topical application of DMBA, a mutagen (Cell, 130:1005-1018, 2007).


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.

Heat shock proteins – a forgotten link in Silkworm breeding for robustness

Silkworm is one of the most thermal-sensitive organisms. Intensive and careful domestication over centuries has apparently deprived the insect of opportunities to acquire thermo tolerance. Among many factors attributed to poor performance of the bivoltine strains under tropical conditions the major aspect is that many quantitative characters decline sharply when temperature is higher than 28°C. The risk of hybridization of polyvoltine to bivoltine could not be taken due to the delay in fixation of economic characters. The long and hard struggle to evolve robust-productive silkworm hybrids has not so far met with satisfactory results.

The front ranking breeders in the field agrees to the fact that it is a difficult task to breed such bivoltine breeds, which are suitable to high temperature environment and yet productive. Therefore means other than the conventional breeding methods are to be adopted to attain the goal. With the aid of modern biotechnological tools it may be possible to quantify the factors responsible for the expression of temperature tolerance. Resistance to high temperature has been recognized as a heritable character in silkworm and the possibility for temperature tolerant silkworm races were suggested by Kato as early as 1989. Thorough understanding of the phenomenon of temperature tolerance in silkworm is an essential pre requisite for attaining any results in this direction.

Extensive studies have been conducted on the heat shock response in insects such as Drosophila, Chironomous, Lymantria dispar, the tobacco hornworm-Manduca sexta, the desert ant-Cataglyphis, the fleshfly-Sarcophaga crassipalpis, the locust Locusta migratoria etc. There are reports on the activity of heat shock proteins in silkworm. Evegnev et al. (1987) studied heat shock response in Bombyx mori cells. Temperature elevation induced active transcription of heat shock mRNAs in infected cells. But at the level of translation headstock treatment failed to induce HSP synthesis and was not able to inhibit production of polyhedrin in such cells.

Joy and Gopinathan in 1995 reported the appearance of 93, 70, 46 and 28 kDa protein bands consequent to high temperature exposure in Bombyx mori in both bivoltine and multivoltine strains, but with varying kinetics. Lee, in 2003 cloned a genomic DNA fragment containing a promoter region for the gene encoding an HSC70-4 homologue, the structure of which was deduced from the partial cDNA sequences that were registered in a Bombyx mori EST date base. The deduced amino acid sequence with 649 residues was 89% and 96% identical to those from Drosophila melanogaster HSC-4 and Manduca sexta HSC-70-4 respectively. The expression analysis by reverse transcription PCR demonstrated that mRNA transcription occurred in all tissues examined and was not stimulated by heat shock. Thus HSC70-4, the molecular chaperon is ubiquitously expressed in every tissue of Bombyx mori.

Considering the enormous investigations conducted on HSPs in a plethora of organisms ranging from bacteria to man, it is felt that there is an acute shortage of literature on the heat shock response of the silkworm Bombyx mori. There is dire necessity for 1. Understanding the molecular mechanism of temperature tolerance in silkworm. 2. Identification of the various families of HSPs synthesized and the threshold temperature, which induce their expression. 3. Understanding the differential expression pattern of various HSPs in bivoltine and polyvoltine races and 4. To locate the genes responsible for the heat inducible HSPs and subsequent steps to introgress the same into the bivoltine genome either by conventional breeding or by use of molecular techniques.

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 involved 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.


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".[3] [4]

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


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 mitochondria/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).

See also


  1. ^ a b Schlesinger, MJ (1990). "Heat shock proteins". THE JOURNAL OF BIOLOGICAL CHEMISTRY 265 (21): 12111-12114. PMID 2197269.
  2. ^ Wall Street Journal article on company and FDA
  3. ^
  4. ^
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Heat_shock_protein". A list of authors is available in Wikipedia.
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