Disease relevance of hsp70

• Preferential activation of HSF-binding activity and hsp70 gene expression in Xenopus heart after mild hyperthermia [1].
• The isolated insert fragment of phage 122 also gives RNA of correct length in heat-treated oocytes which hybridizes to the coding segment of Drosophila hsp70 genes only [2].
• Ag361 shares extensive sequence homology with the hsp70 proteins of Xenopus laevis, Drosophila melanogaster, Escherichia coli, and man, as well as a previously isolated P. falciparum hsp70 protein [3].

High impact information on hsp70

• Transcript levels and translational control of hsp70 synthesis in Xenopus oocytes [4].
• The functional element in the hsp23 gene promoter is located greater than 80 bp further upstream from the TATA box than the relevant element in the hsp70 gene promoter [5].
• In order to understand whether different genes or different promoter elements are involved in the two types of control, several genomic clones coding for Xenopus heat-shock proteins, hsp 70 and hsp 30, were isolated, characterised and tested for expression in oocytes and COS cells [6].
• In contrast, the hsp 70 genes are strongly heat-inducible in COS cells, but their expression is highly efficient in injected oocytes at the normal temperature and is not increased during heat shock [6].
• This represents correct cell type-specific regulation of a cloned reintroduced gene, since the endogenous hsp 70 genes are constitutively activated during oogenesis, leading to the accumulation of stored hsp 70 mRNA in oocytes [6].

Biological context of hsp70

• These studies suggest that the pattern of Xenopus hsp47 gene expression is similar to hsp70 in response to heat shock but also displays unique features including a response to a procollagen-specific stressor and preferential expression in collagen-containing tissues [7].
• Although a subset of the hsp70/68 complex is expressed constitutively in the absence of heat shock in oocytes and embryos (hsc70), actual induction of hsps in response to stress does not occur until the blastula stage when transcription of the zygotic genome is first activated [8].
• For example, a number of heat shock protein genes, such as hsp70, hsp90, and ubiquitin are not heat-inducible until after the midblastula stage of embryogenesis [9].
• No effect was observed with actin mRNA or other hsp70 family members including heat shock cognate 70 and immunoglobulin binding protein [10].
• Continuous exposure of tadpoles to a 33 degrees C heat shock resulted in a coordinate, transient accumulation of hsp 30, hsp 70 and ubiquitin mRNA [11].

Anatomical context of hsp70

• The 26,000-30,000 Mr complex (hsp30/26) was present almost exclusively in a detergent-insoluble fraction, as was 25-50% of the hsp70/68 complex and greater than 50% of hsp56, suggesting that these hsps may be associated with the cytoskeleton during a heat shock [8].
• Exposure of Xenopus laevis A6 kidney epithelial cells to 1 microgram/mL herbimycin A induced the synthesis of the heat shock proteins hsp30 and hsp70 as well as 33- and 45-kDa proteins [12].
• Effect of herbimycin A on hsp30 and hsp70 heat shock protein gene expression in Xenopus cultured cells [12].
• Oocytes injected with hsp70A DNA rapidly accumulate high levels of hsp70 mRNA in their cytoplasm at normal temperature [4].
• In mammals, the heat shock proteins (HSP) gp96 and hsp70 elicit potent specific MHC class I-restricted CD8(+) T cell (CTL) response to exogenous peptides they chaperone [13].

Associations of hsp70 with chemical compounds

• Furthermore A23187 treatment inhibited constitutive accumulation of hsp47 mRNA and retarded heat-induced accumulation of hsp47 and hsp70 mRNA [7].
• Interestingly, hsp47 gene expression but not hsp70 or BiP mRNA accumulation was enhanced by treatment with a procollagen-specific stressor, beta-aminopropionitrile [7].
• Whole-mount in situ hybridization verified the RNA blot analyses and additionally revealed that TSA treatment did not result in any major alterations in the spatial pattern of stress-induced hsp70 or hsp30 mRNA accumulation in early embryos [10].
• Also, exposure of A6 cells to concurrent heat shock and sodium arsenite produced a mild synergistic response with respect to hsp90 mRNA levels in contrast to hsp70 mRNA levels which displayed a strong synergistic effect [14].
• In addition, the synthesis of hsp30 and hsp70 induced by herbimycin A was accompanied by an increase in their mRNAs [12].

Other interactions of hsp70

• These translationally thermotolerant cells displayed relatively high levels of the heat shock proteins hsp30, hsp70, and hsp90 compared to pretreatment at 22, 28, 30, or 35 degrees C. These studies demonstrate that Xenopus A6 cells can acquire a state of thermotolerance and that it is correlated with the synthesis of heat shock proteins [15].
• Given these results, we examined the effect of hyperthermia in vivo on the expression of five hsp genes (hsp70, hsc70, BiP, hsp90, and hsp30) in eye tissue [16].
• In a mutant hsp70 promoter lacking Y boxes, exogenous XHSF1 activates transcription from a chromatin template much more efficiently under heat shock conditions [17].
• When oocytes are first activated by electric shock or ionophore treatment, followed by immunoprecipitation using anti-centrin monoclonal antibody 20H5, centrin precipitates with significantly reduced levels of hsp-70 in the complex, and these complexes contain no apparent hsp-90 [18].

Analytical, diagnostic and therapeutic context of hsp70

• Titration of chromatin in vivo leads to constitutive transcription from the wild-type hsp70 promoter [17].
• Western blot analysis of immunoprecipitates using anti-hsp monoclonal antibodies (N27 and AC-88) confirms the identity of the 70-kDa protein as hsp-70 and identifies the 90-kDa protein as hsp-90 [18].

References