Disease relevance of Hsp83

• In E. coli the protein homologous to hsp83 is a heat shock protein called C62 [1].
• The conceptual translation of Osvaldo ORF1 exhibits sequence homology to HIV1 and SIV capsid (p24) and nucleocapsid (p7) mature proteins [2].
• Treatment of FHV-infected Drosophila S2 cells with the Hsp90-specific inhibitor geldanamycin or radicicol potently suppressed the production of infectious virions and the accumulation of protein A and genomic, subgenomic, and template viral RNA [3].
• Two Hsp82 genes were isolated from the malaria vector Anopheles albimanus in a single lambda phage clone [4].
• The ORF1 exhibits sequence homology to matrix, capsid and nucleocapsid gag proteins and ORF2 encodes a putative protease (PR), a reverse transcriptase (RT), an Rnase H (RH) and an integrase (IN) region [5].

Psychiatry related information on Hsp83

• Consistent with the protective effect of heat-shock genes, was the observation that flies carrying a mutation for the heat-shock protein Hsp83 (Hsp83(08445)) showed exaggerated homeostatic response and died after sleep deprivation [6].

High impact information on Hsp83

• The altered chromatin state is evidenced by ectopic expression of the morphogen wingless in eye imaginal discs and a corresponding abnormal eye phenotype, both of which are epigenetically heritable in subsequent generations, even when function of Hsp90 is restored [7].
• Signaling by the sevenless receptor, required for differentiation of the R7 photoreceptor neuron in Drosophila, is reduced by mutations in E(sev)3A and E(sev)3B [8].
• The complete I factor sequence contains two long open reading frames, ORF1 and ORF2, of 1278 and 3258 bp [9].
• ORF1 encodes a possible nucleic acid-binding protein, and part of the amino acid sequence of ORF2 is similar to that of viral reverse transcriptases and polypeptides encoded by L1 elements [9].
• During normal development in D. melanogaster, messenger RNAs for three of the seven heat shock proteins (hsp83, hsp28 and hsp26) accumulate in adult ovaries and are abundant in embryos until blastoderm [10].

Biological context of Hsp83

• Thermoprotection of synaptic transmission in a Drosophila heat shock factor mutant is accompanied by increased expression of Hsp83 and DnaJ-1 [11].
• The mutations result in single amino acid substitutions in the Hsp83 protein and cause a dominant-negative effect on the function of the wild-type protein [12].
• Dynamic Hsp83 RNA localization during Drosophila oogenesis and embryogenesis [13].
• We show that maternally synthesized Hsp83 transcripts are localized to the posterior pole of the early Drosophila embryo by a novel mechanism involving a combination of generalized RNA degradation and local protection at the posterior [13].
• The first of these, introducing entire chromosomes carrying either of two Hsp83 mutations, did not increase shape variation or asymmetry over a wild-type control in any of the nine genetic backgrounds [14].

Anatomical context of Hsp83

• In addition, we show that zygotic expression of Hsp83 commences in the anterior third of the embryo at the syncytial blastoderm stage and is regulated by the anterior morphogen, bicoid [13].
• Mislocalization of oskar RNA to the anterior pole, which has been shown to result in induction of germ cells at the anterior, leads to anterior protection of maternal Hsp83 RNA [13].
• The accumulation in normal oogenesis of mRNAs for only three of the seven heat shock proteins indicates the existence of differential, possibly multiple controls of heat shock gene expression, and suggests that heat shock proteins hsp83, hsp28 and hsp26 function in the oocyte or early embryo [10].
• This suggests that another role of Hsp90 might be to ensure proper centrosome function [15].
• These results identify Hsp90 as a host factor involved in FHV RNA replication and suggest that FHV uses established cellular chaperone pathways to assemble its RNA replication complexes on intracellular membranes [3].

Associations of Hsp83 with chemical compounds

• Poly(A) tails of Hsp83 are approximately 30 nucleotides long, as common for other low eukaryotes [16].
• Disruption of Hsp90 function by mutations in the Drosophila gene or treatment of mammalian cells with the Hsp90 inhibitor geldanamycin, results in abnormal centrosome separation and maturation, aberrant spindles and impaired chromosome segregation [15].
• Treatment of cells with several benzoquinone ansamycin inhibitors of Hsp90 (geldanamycin, herbimycin A) activated a heat shock response in the absence of heat shock, as reported previously [17].
• Hsp90 is a molecular chaperone associated with the folding of signal-transducing proteins, such as steroid hormone receptors and protein kinases [18].
• The heat shock protein Hsp90 has been shown to associate with various cellular signalling proteins such as steroid hormone receptors, src-like kinases and the serine/threonine kinase Raf [12].

Physical interactions of Hsp83

• Topoisomerase I also interacted with the DNA throughout the transcriptionally active hsp83 gene, including an intron, in both heat-shocked and non-heat-shocked cells [19].
• We provide evidence that Aurora B interacts with and requires the Cdc37/Hsp90 complex for its stability [20].

Regulatory relationships of Hsp83

• The mei-218 mutant phenotype has been rescued by germline transformation with both a genomic fragment and a cDNA under the control of the hsp83 promoter [21].

Other interactions of Hsp83

• Here, we investigated the transcriptional regulation of other heat-shock-responsive genes (Hsp23, Hsp26, Hsp83 and Hsrw) in D. triauraria with relation to diapause [22].
• We detected no effect of the hormone on the synthesis of heat shock polypeptides hsp68, hsp70, and hsp83 [23].
• This protection of Hsp83 RNA occurs in wild-type embryos and embryos produced by females carrying the maternal effect mutations nanos and pumilio, which eliminate components of the posterior polar plasm without disrupting polar granule integrity [13].
• In smaug mutants, degradation of Hsp83 transcripts is not triggered, and, thus, localization does not occur [24].
• Reduction of CCR4 protein levels compromises Hsp83 transcript destabilization [24].

Analytical, diagnostic and therapeutic context of Hsp83

• 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 [11].
• This association between Hsp90 and the centrosome can be observed in purified centrosomes and after treatment with microtubule depolymerizing drugs, two criteria normally used to define core centrosomal components [15].
• The heat-shock protein Hsp90 supports diverse but specific signal transducers and lies at the interface of several developmental pathways [25].
• Based on in situ hybridization on polytene chromosomes, cDNA and genomic clone mapping, nucleotide sequencing, and genomic Southern analysis, hsp83 is shown to be present as a single-copy gene at locus 64B on the 3L chromosome arm in D. auraria [26].
• Northern blot analysis with HSP genomic probes from Drosophila sp showed that (1) the probe for HSP 82 hybridized with an RNA of 2.6 kb present only in heat-shocked cells, (2) the HSP 70 probe hybridized with RNA species of 2.5 kb, present only in RNA from heat-shocked cells [27].

References