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.
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.
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.
These activities are part of a cell's own repair system, called the "cellular stress response" or the "heat-shock response".
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 Factor 1 (HSF1) is a transcription factor that is involved in the upregulation of Hsp70 protein expression. Recently it was discovered that HSF1 is a powerful multifaceted modifier of carcinogenesis. HSF1 knockout mice show significantly decreased incidence of skin tumor after topical application of DMBA (7,12-dimethylbenzanthracene), a mutagen.
Intracellular heat shock proteins are highly expressed in cancerous cells and are essential to the survival of these cell types. Hence small molecule inhibitors of Hsps, especially Hsp90 show promise as anticancer agents. The potent Hsp90 inhibitor 17-AAG is currently in clinical trials for the treatment of several types of cancer.
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 et.al., 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.
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.
|Approximate molecular weight (kDa)||Prokaryotic proteins||Eukaryotic proteins||Function|
|20-30 kDa||GrpE||The HspB group of Hsp. Ten members in mammals including Hsp27 or HspB1|
|40 kDa||DnaJ||Hsp40||Co-factor of Hsp70|
|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).
Transcriptional profiling of Arabidopsis heat shock proteins and transcription factors reveals extensive overlap between heat and non-heat stress response pathways.(Research article)
May 22, 2007; Authors: William R Swindell (corresponding author) ; Marianne Huebner ; Andreas P Weber BackgroundThe heat shock...