Disease relevance of Hsp70Ba

• Hsp70 gene transfer by adeno-associated virus inhibits MPTP-induced nigrostriatal degeneration in the mouse model of Parkinson disease [1].
• The set of 19 hsp70-controlled lef ORFs (HSEpiHis lef library) supports transient expression from a late viral promoter. lef-12 did not affect expression from an early baculovirus promoter [2].
• Recently, Hsp70 was shown to inhibit alpha-synuclein toxicity in a Drosophila model of inherited PD [1].
• The steric accessibility of the scs region before heat shock was 3-fold higher than either flanking region (consistent with its previously documented DNase I hypersensitivity); this increased an additional 2-fold following hsp70 gene activation without a concomitant rise in the accessibility of flanking regions [3].
• Caulobacter crescentus has a single dnaK gene that is highly homologous to the hsp70 family of heat shock genes [4].

High impact information on Hsp70Ba

• In agreement with previous in vitro studies, we find that the heat shock-mediated transcriptional induction of the hsp70 genes perturbs their chromatin structure, resulting in fewer protein-DNA contacts crosslinkable in vivo by formaldehyde [5].
• When fused to an hsp70 heat shock promoter and introduced into the germ line by P-element-mediated transformation, ftz could be overexpressed at all stages of development by heat shock [6].
• We show that Pcf11 is directly involved in termination in Drosophila. dPcf11 is concentrated at the 3' end of the hsp70 gene in cells, and depletion of dPcf11 with RNAi causes Pol II to readthrough the normal region of termination. dPcf11 also localizes to most transcribed loci on polytene chromosomes [7].
• Constitutively expressed 18S ribosomal RNA genes also exhibited unrestrained superhelical tension at a level comparable with that across hsp70 [8].
• Four genes (ums1, ums2, ums3 and ums4) representing an hsp70-related gene family were isolated from a genomic library of Ustilago maydis [9].

Chemical compound and disease context of Hsp70Ba

• We show that Hsp70 gene transfer to dopamine neurons by a recombinant adeno-associated virus significantly protects the mouse dopaminergic system against MPTP-induced dopamine neuron loss and the associated decline in striatal dopamine levels and tyrosine hydroxylase-positive fibers [1].

Biological context of Hsp70Ba

• A human gene family with sequence homology to Drosophila melanogaster Hsp70 heat shock genes [10].
• One lambda clone was sequenced and characterized as a hsp70 pseudogene inserted into a rearranged human HindIII 1.9-kilobase repeated DNA sequence [10].
• Here we report remarkable genetic differentiation of microsatellites and divergence in the regulatory region of hsp70Ba which encodes the major inducible heat shock protein of Drosophila, in the two populations [11].
• A polymer of 40 tandem copies of the pair of regulatory elements of the hsp70 gene was constructed and cloned into a plasmid vector [12].
• Promoter function for hsp70 gene expression in Drosophila melanogaster was studied with an in vivo competition assay [12].

Anatomical context of Hsp70Ba

• Hsp70 expression was restricted only within the testis lobes of male, while ovary in the female fly did not exhibit any Hsp70 expression [13].
• Hsp70 reduced MPTP-induced apoptosis in the substantia nigra, and unilateral protection of the dopaminergic system by Hsp70 was associated with increased amphetamine-induced turning toward the uninjected side [1].
• A nearly full-length cDNA clone isolated from the rat pheochromocytoma cell line, PC12, revealed extensive nucleotide sequence similarity between the rat cDNA and the Drosophila melanogaster hsp70 gene [14].
• Finally, trout hsp70 cDNA sequences cross-hybridized with restriction fragments in genomic DNA from HeLa cells, bovine liver, Caenorhabditis elegans, and D. melanogaster [15].
• Thus, in contrast to the situation in COS-1 cells, the previously defined heat shock consensus sequence which is located between nucleotides 62 and 48 of the hsp70 gene 5' nontranscribed DNA segment is not sufficient for the expression of the D. melanogaster gene in homologous cells [16].

Associations of Hsp70Ba with chemical compounds

• The present study indicates a profound effect on reproduction by cypermethrin and suggests the protective role of hsp70 [13].
• As reported previously, overexpression of heat-shock protein 70 (Hsp70) rescues polyglutamine-dependent lethality [17].
• Here we tested the potential of Hsp70 (approved gene symbol HSPA1A) for gene therapy in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of idiopathic PD [1].
• Northern blot analysis of RNA from arsenite-induced RTG-2 cells, with the trout hsp70 cDNAs as probes, revealed the presence of three hsp70 mRNA species [15].
• hsp70 mRNA accumulates in LLC-PK1 pig kidney cells treated with calcitonin but not with 8-bromo-cyclic AMP [18].

Analytical, diagnostic and therapeutic context of Hsp70Ba

• However, contrary to earlier in vitro evidence that histones may be absent from actively transcribed genes, we show directly, by immunoprecipitation of in vivo-crosslinked chromatin fragments, that at least histone H4 remains bound to hsp70 DNA in vivo, irrespective of its rate of transcription [5].
• In the present study we demonstrate the utility of transgenic Drosophila as an alternative animal model for evaluating hazardous effects of the effluent from the chrome plating industry and further reveal the cytoprotective role of hsp70 and its expression as an early marker in environmental risk assessment [19].
• Drosophila heat shock protein 70 promoter (hsp70), cytomegalovirus, and simian virus early promoters, controlling the luciferase gene, were transfected into the cell cultures using liposomes [20].
• In addition, increases in the levels of Hsp83 and DnaJ-1 proteins but not in the inducible form of Hsp70 were detected by Western blot analysis [21].
• The presence of general transcription factors and other coactivators at the Drosophila hsp70 gene promoter in vivo has been examined by polytene chromosome immunofluorescence and chromatin immunoprecipitation at endogenous heat-shock loci or at a hsp70 promoter-containing transgene [22].

References