Disease relevance of Hsp90aa1

• High constitutive transcription of HSP86 gene in murine embryonal carcinoma cells [1].
• Disruption of the EF-2 kinase/Hsp90 protein complex: a possible mechanism to inhibit glioblastoma by geldanamycin [2].
• Modulation of Hsp90 function in neurodegenerative disorders: a molecular-targeted therapy against disease-causing protein [3].
• 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a novel Hsp90 inhibitor, is a new derivative of geldanamycin that shares its important biological activities but shows less toxicity [3].
• We sought to determine the in vivo effects of Hsp90 inhibitor compounds on human neuroblastomas [4].

High impact information on Hsp90aa1

• Modulating molecular chaperone Hsp90 functions through reversible acetylation [5].
• Regulation of the Src family kinase Lck by Hsp90 and ubiquitination [6].
• Surprisingly, transcription run-on assays suggest that HSF2 in unstressed EC cells does not stimulate transcription of two putative target genes, hsp70 and hsp86 [7].
• A comparison of HSP84 and HSP86 mRNA expression in adult mouse tissues revealed distinct expression patterns for these highly homologous genes [8].
• Expression of HSP86 in male germ cells [8].

Chemical compound and disease context of Hsp90aa1

• Our proposed therapeutic approach, modulation of Hsp90 function by 17-AAG treatment, has emerged as a candidate for molecular-targeted therapies for neurodegenerative diseases [3].

Biological context of Hsp90aa1

• Hsp86-related sequences were assigned to chromosomes 12, 11, and 3 [9].
• Sequences from a number of peptides from HSP86 were found to be in complete agreement with the nucleotide sequence [9].
• The HSP86 gene family in BALB/c, AKR/J, C58/J, and NFS/N inbred mice comprises an intron-containing expressed gene and, depending on the strain, two to four other HSP86-related members that are apparently processed pseudogenes [10].
• Therefore, as a step towards understanding the molecular basis for the differential regulation of these two genes, we have isolated and characterized genomic clones of the murine hsp86 gene and its 5' flanking region [11].
• In mice the expression of these two genes, hsp84 and hsp86, vary with respect to each other in responses to stress, and also in response to signals for growth and development [11].

Anatomical context of Hsp90aa1

• HSP86 was most abundant in the germ cell population and was present at significantly lower levels in the somatic cells [12].
• This study extends to the protein level our previous observations, which had established the stage and cellular specificity of expression of hsp86 and hsp84 in the murine testis in the absence of exogenous stress [12].
• In order to investigate HSP86 heat-shock gene expression in embryonal carcinoma cell lines (EC), a partial mouse HSP86 cDNA clone was isolated and characterized [1].
• Although mRNA stabilization is suggested to account in part of the high constitutive expression of the heat-shock-like protein HSC73 in F9 cells, HSP86 RNA appears as stable in fibroblasts as in F9 cells [1].
• Heat shock protein 90 (Hsp90) is an abundant protein and essential for all eukaryotic cells [13].

Associations of Hsp90aa1 with chemical compounds

• Here we establish that following TCR stimulation, endogenous activated Lck in T cells is also degraded in the presence of the Hsp90 inhibitor geldanamycin [6].
• We now report that this regulation occurred with both the HSP86 and HSP84 forms of HSP90 as well as with the 94-kilodalton glucose-regulated protein [14].
• Treatment of cell lines for 24-48 h of GA or 17-AAG disrupted EF-2-kinase/Hsp90 interactions as measured by coimmunoprecipitation, resulting in a decreased amount of recoverable kinase in cell lysates [2].
• Geldanamycin (GA) is a benzoquinone ansamycin antibiotic that disrupts Hsp90-protein interactions [2].
• In addition, UCS15A appeared to differ from src-destabilizing agents such as herbimycin and radicicol that destabilize src by interfering with Hsp90 [15].

Other interactions of Hsp90aa1

• The findings presented herein suggest that HSP86 and HSP84 may have different functions [9].
• Also, an HSP86-related locus that was unique to NFS/N mice, designated Hsp86-ps4, was mapped to Chromosome 4 [10].
• An HSP86-related locus specific to NFS/N and C58/J mice, designated Hsp86-ps3, was mapped on Chromosome 9 [10].
• The three main immunogenic HSPs, gp96, hsp86/84, and hsc70 can be further isolated to homogeneity using additional purification methods [16].
• Hsc73, Hsj2, and Hsp86 were shown in our previous study to be differentially expressed in the mouse embryonic mandible at day 10.5 (E10.5) gestational age [17].

Analytical, diagnostic and therapeutic context of Hsp90aa1

• Immunoprecipitation analysis revealed that a 70-kDa protein coprecipitated with the HSP86/HSP84 proteins in testicular homogenates [12].
• Heat-shock proteins, Hsp84 and Hsp86, of mice and men: two related genes encode formerly identified tumour-specific transplantation antigens [18].
• We verified array results with RT-PCR and Northern blotting for three genes which are related to oxidative damage closely, including Hsp84, Hsp86 and YB-1 [19].
• Identification of new biomarkers for clinical trials of Hsp90 inhibitors [20].
• Inhibition of neuroblastoma xenograft growth by Hsp90 inhibitors [4].

References