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Gene Review

Hsp70Aa  -  Heat-shock-protein-70Aa

Drosophila melanogaster

Synonyms: 87A, CG31366, Dm-hsp70, DmHSP70AA, Dmel\CG31366, ...
 
 
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Disease relevance of Hsp70Aa

  • Recently, Hsp70 was shown to inhibit alpha-synuclein toxicity in a Drosophila model of inherited PD [1].
  • 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].
  • 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].
 

Psychiatry related information on Hsp70Aa

  • Furthermore, we did not detect any advantage of Drosophila overexpressing hsp70 on the two measurements of locomotor activity [5].
 

High impact information on Hsp70Aa

  • Induction of ectopic sim protein under the control of the hsp70 promoter shows that sim can direct cells of the lateral CNS to exhibit midline cell morphology and patterns of gene expression [6].
  • Purified Ftz directly activates in vitro transcription by binding to homeodomain binding sites inserted upstream of the TATA box of the Drosophila hsp70 promoter [7].
  • 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 [8].
  • Such an enhancer can also be generated by duplication of HSE sequences from the Drosophila hsp70 promoter, which were previously identified as an upstream promoter element and are known to bind a purified heat shock transcription factor in vitro [9].
  • Transcription studies in vitro on the 5' deletions with nuclear extracts and reconstitution experiments show that the TATA proximal site alone, is insufficient for maximal transcriptional activation of the hsp 70 gene [10].
 

Chemical compound and disease context of Hsp70Aa

 

Biological context of Hsp70Aa

  • 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 [12].
  • The primary sequence of approximately one-third of the protein-coding region has been compared with that of the hsp70 gene; 72% homology of the base sequence and 74% homology of the deduced amino acid sequence was found [13].
  • In the codon specifying amino acid 66, the hsc70 gene contains an insertion of 1.7 kilobases; the hsp70 genes contain no intervening sequences [13].
  • The Drosophila scs and scs' insulators localize near the borders of a structural domain in the polytene chromosomes, known as a puff, produced by transcription of the 87A heat shock protein (hsp) genes [14].
  • 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 [15].
 

Anatomical context of Hsp70Aa

  • Hsp70 expression was restricted only within the testis lobes of male, while ovary in the female fly did not exhibit any Hsp70 expression [16].
  • Approximately one in two nucleosomes of the transcribed copia and heat-shock 70 (hsp 70) genes in nonshocked cultured cells contains ubiquitin-H2A (uH2A) semihistone, a covalent conjugate of histone H2A and a small protein, ubiquitin [17].
  • High levels of hsp70 can be produced in unstressed COS cells by transfecting them with an appropriate expression plasmid [18].
  • Furthermore, heat shock does not prevent shrinkage of their nucleoli in the presence of actinomycin, which indicates that ribosome export also recovers rapidly when pre-synthesized hsp70 is present [18].
  • 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].
 

Associations of Hsp70Aa with chemical compounds

  • The present study indicates a profound effect on reproduction by cypermethrin and suggests the protective role of hsp70 [16].
  • 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].
  • Responses of Drosophila heat shock 70 gene (hsp70) were used to establish heat shock temperatures and cadmium (Cd) concentrations for Chironomus experiments and to validate DD [19].
  • Our results showed a strong hsp70 expression in the Captafol-exposed larvae followed by weaker expression in Captan- and Folpet-treated larvae [20].
  • The present study suggests that (a). hsp70 induction is sensitive enough to be used as a biomarker against phthalimide group of chemicals, (b). amongst the three test chemicals, Captafol is the most deleterious compound followed by Captan and Folpet, (c) [20].
 

Analytical, diagnostic and therapeutic context of Hsp70Aa

  • We have analyzed the proteins made by embryos lacking either 87A or 87C, and have compared the 87A- and 87C-coded hsp 70 by isoelectric focusing and tryptic peptide fingerprinting [21].
  • 550 bp upstream from the 5' end of the hsp 70 mRNA, there is a very A+T rich region shown by heteroduplex analysis to be also present at the same position in other hsp 70 genes9 [22].
  • By saturation in situ hybridization, the length of the transcribed region at 93D is twice that of the mRNA coding region at the heat shock puff site 87A [23].
  • 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 [24].
  • 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 [8].

References

  1. Hsp70 gene transfer by adeno-associated virus inhibits MPTP-induced nigrostriatal degeneration in the mouse model of Parkinson disease. Dong, Z., Wolfer, D.P., Lipp, H.P., Büeler, H. Mol. Ther. (2005) [Pubmed]
  2. Nineteen baculovirus open reading frames, including LEF-12, support late gene expression. Rapp, J.C., Wilson, J.A., Miller, L.K. J. Virol. (1998) [Pubmed]
  3. Specialized chromatin structure domain boundary elements flanking a Drosophila heat shock gene locus are under torsional strain in vivo. Jupe, E.R., Sinden, R.R., Cartwright, I.L. Biochemistry (1995) [Pubmed]
  4. Expression of the Caulobacter heat shock gene dnaK is developmentally controlled during growth at normal temperatures. Gomes, S.L., Gober, J.W., Shapiro, L. J. Bacteriol. (1990) [Pubmed]
  5. Locomotor activity as a function of age and life span in Drosophila melanogaster overexpressing hsp70. Minois, N., Khazaeli, A.A., Curtsinger, J.W. Exp. Gerontol. (2001) [Pubmed]
  6. The Drosophila single-minded gene encodes a helix-loop-helix protein that acts as a master regulator of CNS midline development. Nambu, J.R., Lewis, J.O., Wharton, K.A., Crews, S.T. Cell (1991) [Pubmed]
  7. Binding site-dependent direct activation and repression of in vitro transcription by Drosophila homeodomain proteins. Ohkuma, Y., Horikoshi, M., Roeder, R.G., Desplan, C. Cell (1990) [Pubmed]
  8. Mapping protein-DNA interactions in vivo with formaldehyde: evidence that histone H4 is retained on a highly transcribed gene. Solomon, M.J., Larsen, P.L., Varshavsky, A. Cell (1988) [Pubmed]
  9. Heat shock regulatory elements function as an inducible enhancer in the Xenopus hsp70 gene and when linked to a heterologous promoter. Bienz, M., Pelham, H.R. Cell (1986) [Pubmed]
  10. Sequences required for in vitro transcriptional activation of a Drosophila hsp 70 gene. Topol, J., Ruden, D.M., Parker, C.S. Cell (1985) [Pubmed]
  11. Chaperoning brain degeneration. Bonini, N.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  12. The Drosophila P68 RNA helicase regulates transcriptional deactivation by promoting RNA release from chromatin. Buszczak, M., Spradling, A.C. Genes Dev. (2006) [Pubmed]
  13. Drosophila gene related to the major heat shock-induced gene is transcribed at normal temperatures and not induced by heat shock. Ingolia, T.D., Craig, E.A. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  14. Studies of the role of the Drosophila scs and scs' insulators in defining boundaries of a chromosome puff. Kuhn, E.J., Hart, C.M., Geyer, P.K. Mol. Cell. Biol. (2004) [Pubmed]
  15. 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. Lo, J.F., Hayashi, M., Woo-Kim, S., Tian, B., Huang, J.F., Fearns, C., Takayama, S., Zapata, J.M., Yang, Y., Lee, J.D. Mol. Cell. Biol. (2004) [Pubmed]
  16. Synthetic Pyrethroid Cypermethrin Induced Cellular Damage in Reproductive Tissues of Drosophila melanogaster: Hsp70 as a Marker of Cellular Damage. Mukhopadhyay, I., Siddique, H.R., Bajpai, V.K., Saxena, D.K., Chowdhuri, D.K. Arch. Environ. Contam. Toxicol. (2006) [Pubmed]
  17. Selective arrangement of ubiquitinated and D1 protein-containing nucleosomes within the Drosophila genome. Levinger, L., Varshavsky, A. Cell (1982) [Pubmed]
  18. Hsp70 accelerates the recovery of nucleolar morphology after heat shock. Pelham, H.R. EMBO J. (1984) [Pubmed]
  19. Identification of a putative ribosomal protein mRNA in Chironomus riparius and its response to cadmium, heat shock, and actinomycin D. Govinda, S., Kutlow, T., Bentivegna, C.S. J. Biochem. Mol. Toxicol. (2000) [Pubmed]
  20. Induction of hsp70 in transgenic Drosophila: biomarker of exposure against phthalimide group of chemicals. Nazir, A., Saxena, D.K., Kar Chowdhuri, D. Biochim. Biophys. Acta (2003) [Pubmed]
  21. Deletion mapping of two D. melanogaster loci that code for the 70,000 dalton heat-induced protein. Ish-Horowicz, D., Pinchin, S.M., Gausz, J., Gyurkovics, H., Bencze, G., Goldschmidt-Clermont, M., Holden, J.J. Cell (1979) [Pubmed]
  22. Nucleotide sequences of heat shock activated genes in Drosophila melanogaster. I. Sequences in the regions of the 5' and 3' ends of the hsp 70 gene in the hybrid plasmid 56H8. Török, I., Karch, F. Nucleic Acids Res. (1980) [Pubmed]
  23. Transcription and metabolism of RNA from the Drosophila melanogaster heat shock puff site 93D. Lengyel, J.A., Ransom, L.J., Graham, M.L., Pardue, M.L. Chromosoma (1980) [Pubmed]
  24. Thermoprotection of synaptic transmission in a Drosophila heat shock factor mutant is accompanied by increased expression of Hsp83 and DnaJ-1. Neal, S.J., Karunanithi, S., Best, A., So, A.K., Tanguay, R.M., Atwood, H.L., Westwood, J.T. Physiol. Genomics (2006) [Pubmed]
 
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