Disease relevance of Hsp70Ab

• 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 [1].
• Hsp70 gene transfer by adeno-associated virus inhibits MPTP-induced nigrostriatal degeneration in the mouse model of Parkinson disease [2].
• Recently, Hsp70 was shown to inhibit alpha-synuclein toxicity in a Drosophila model of inherited PD [2].
• 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 Hsp70Ab

• 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].
• Full-length hsp70 mRNA accumulates in the nucleus near its sites of transcription following heat shock of p68 homozygotes, and hsp70 gene shutdown is delayed [6].
• Prior to heat shock, GAGA protein is associated with the promoter regions of the uninduced hsp70 and hsp26 genes [7].
• 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 [8].
• 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 [9].

Chemical compound and disease context of Hsp70Ab

• 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 [2].

Biological context of Hsp70Ab

• Tid1, a cochaperone of the heat shock 70 protein and the mammalian counterpart of the Drosophila tumor suppressor l(2)tid, is critical for early embryonic development and cell survival [10].
• A human gene family with sequence homology to Drosophila melanogaster Hsp70 heat shock genes [11].
• One lambda clone was sequenced and characterized as a hsp70 pseudogene inserted into a rearranged human HindIII 1.9-kilobase repeated DNA sequence [11].
• These results indicate that the compensatory upregulation of constitutively expressed Hsps, in the absence of the synthesis of the major inducible Hsp, Hsp70, could still provide substantial thermoprotection to both synapses and the whole organism [12].
• The recruitment of GAGA protein to the hsp70 gene after an instantaneous heat shock occurs in a 5' to 3' manner with kinetics similar to RNA polymerase [7].

Anatomical context of Hsp70Ab

• 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 [2].
• IE1 was also an effective initiator of transcription, particularly in two Anopheles cell lines, but generally it performed less well than the actin 5C promoter and was also outperformed by hsp70 in Anopheles gambiae cells [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 Hsp70Ab with chemical compounds

• The present study indicates a profound effect on reproduction by cypermethrin and suggests the protective role of hsp70 [13].
• 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 [2].
• In C6/36 cells, the actin 5C and hr5-ie1 promoters were significantly more active than the hsp70 promoter [17].
• Overall, the actin 5C promoter was considerably more effective at driving luciferase expression than either hsp70 or IE1 in cell lines derived from Anopheles, Aedes and Culex species. hsp70 functioned well when induced by heat shock and was also induced to a lesser extent by chemicals such as sodium arsenite [14].
• We predict that the molecular mechanisms underlying ethanol regulation of Hsc70, GRP94 and GRP78 may be similar since they have related functions [18].

Regulatory relationships of Hsp70Ab

• We have made transgenic flies bearing dominant inhibitory (N17DRacA), and wild-type versions of the DRacA cDNA under control of an Hsp70 promoter [19].
• To examine RnRacGAP function, we generated transgenic strains expressing RnRacGAP under the control of the heat-shock promoter hsp70 [20].

Other interactions of Hsp70Ab

• Strong reductions of nucleotide variability and linkage disequilibria among conversion-mediated sites in hsp70Ab and hsp70Bb alleles sampled from a single natural population are consistent with a selective sweep [21].

Analytical, diagnostic and therapeutic context of Hsp70Ab

• 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 [12].
• 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 [22].
• Heat shock mRNA was monitored by hybridization of Northern blots with the Drosophila hsp-70 gene probe and an inducible member of the yeast hsp-70 gene family, YG100 [23].
• 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 [24].

References