Disease relevance of HSP104

• The HSP104 gene, which is largely responsible for induced thermotolerance in yeast, was necessary for life extension induced by transient heat stress [1].
• The thermoprotective effect in anaerobic cells was not due to expression of HSP104 or any other heat shock gene, raising the possibility that the toxicity of lethal heat shock is due mainly to oxidative stress [2].
• Hsp104 cooperates with the chaperones present in reticulocyte lysates but not with DnaK of E. coli [3].
• Here we investigate the role of Hsp104 in vivo using a temperature-sensitive Vibrio harveyi luciferase-fusion protein as a test substrate [4].
• Hsp104 transgenic and control littermates were infected intracerebrally with the ME7 strain of scrapie [5].

Psychiatry related information on HSP104

• Overexpression of yeast hsp104 reduces polyglutamine aggregation and prolongs survival of a transgenic mouse model of Huntington's disease [6].

High impact information on HSP104

• In Saccharomyces cerevisiae, heat-shock protein hsp104 is vital for tolerance to heat, ethanol and other stresses [7].
• Mutagenesis of two putative nucleotide-binding sites in hsp104 indicates that both are essential for function in thermotolerance [7].
• Furthermore, RNA in situ hybridization analysis demonstrates that loss of Hmt1 results in slowed release of HSP104 mRNA from the sites of transcription [8].
• Sequence analysis of a 102-kD protein, identified previously as a specific Omega RNA-binding protein, revealed homology to the HSP101/HSP104/ClpB family of heat shock proteins and its expression in yeast complemented a thermotolerance defect caused by a deletion of the HSP104 gene [9].
• A protein-remodeling factor, Hsp104, controls the inheritance of several yeast prions, including those formed by Sup35 and Ure2 [10].

Chemical compound and disease context of HSP104

• Deletion of the TPS1 gene, encoding the first enzyme in the biosynthesis of trehalose, or the heat shock protein gene HSP104 only resulted in a minor effect on heat stress resistance compared with deletion of these genes in a wild-type background [11].
• Small Hsps partially suppress toxicity, even in the absence of Hsp104, potentially by sequestering polyglutamine from toxic interactions with other proteins [12].
• Strikingly, deletion of Hsp104 increases the size of inclusions formed by expanded poly(Q) lacking the proline-rich region and abolishes toxicity [13].

Biological context of HSP104

• Excess of Sfl1, Ssn8, and Rpp0 influenced at least one of the tested chaperone-specific promoters, SSA4, HSP104, and model promoters, with either the heat shock or stress response elements [14].
• Intracellular levels of Hsp104 and trehalose, which were reportedly required for the acquisition of heat tolerance in the stationary phase of cell growth, were affected in both GTS1 mutants roughly in proportion to the gene dosage of GTS1, whereas those of other Hsps were less affected [15].
• The mRNA levels of genes for Hsp104 and trehalose-6-phosphate synthase 1 changed as a function of GTS1 gene dosage [15].
• Upregulation of the Hsp104 chaperone at physiological temperature during recovery from thermal insult [16].
• Destruction of HSE plus all three STREs abolished Hsp104 expression, resulting in cell death after thermal insult [16].

Anatomical context of HSP104

• The results obtained clearly indicate that a mild heat shock elicits a hyperpolarization of the inner mitochondrial membrane and such an event is one of several signals triggering the chain of reactions that activates the expression of the HSP104 gene and probably the expression of other heat shock-regulated genes in S. cerevisiae [17].
• When expressed in the cytosol, Hsp78 can substitute for the homologous heat shock protein Hsp104 in mediating cellular thermotolerance, suggesting a conserved mode of action of the two proteins [18].
• It has been speculated that trehalose protects proteins and membranes under environmental stress conditions, but recently it was shown to assist the Hsp104 chaperone in refolding of heat-damaged proteins in the yeast cytosol [19].
• With several independent clone cells of transformants, the levels of luciferase activity and some hsps, such as hsp104, hsp90, hsp70 and hsp26, were examined [20].
• The cytoplasmic chaperone hsp104 is required for conformational repair of heat-denatured proteins in the yeast endoplasmic reticulum [21].

Associations of HSP104 with chemical compounds

• Upon return to 30 degrees C, TPS1, TPS2, and HSP104 mRNAs, trehalose levels and tolerance to freezing fall dramatically within minutes [22].
• Respiratory deficiency of MB43-nam9-1 is overcome by transient overexpression of HSP104, by deletion of HSP104, by transient exposure to guanidine hydrochloride, and by expression of the C-terminal portion of Sup35, indicating an involvement of the yeast prion [PSI(+)] [23].
• Trehalose, glucose-6-phosphate, UDP-glucose, and ATP, were all found to increase during the 40 min heat treatment at 39 degrees C. Since this also occurs in a mutant lacking the heat shock-induced protein HSP104 (delta hsp104), this protein cannot be involved in the accumulation of trehalose under these heat shock conditions [24].
• HSP12 and HSP104 were transcribed 10 h earlier with maltose than with glucose [25].
• The same effect was seen in the tps1 (trehalose-6-phosphate synthase) hsp104 double mutant, suggesting that the extreme heat shock sensitivity was due mainly to a lack of trehalose rather than to the presence of trehalose-6-phosphate [26].

Physical interactions of HSP104

• Indeed, we find that a pool of heat shock HSP104 transcripts are 3'-end truncated in THO complex mutant as well as sub2 mutant backgrounds [27].
• Binding to these promoters is rapidly induced by heat stress at 39 degrees . HSF binds to ScSSA1 and HSP104 promoters under non-stress conditions, but at a low level [28].
• Hsp104 interacts with Hsp90 cochaperones in respiring yeast [29].
• Hsp104 binds to yeast Sup35 prion fiber but needs other factor(s) to sever it [30].

Enzymatic interactions of HSP104

• We propose that Hsp104p plays a role in establishing stable [psi+] inheritance by splitting up Sup35p aggregates and thus ensuring equidistribution of the prion-like Sup35p isoform to daughter cells at cell divisions [31].

Regulatory relationships of HSP104

• Overproduction of the unrelated chaperone protein Hsp82 (Hsp90) neither cured [PSI] nor antagonized the [PSI]-curing effect of overproduced Hsp104 [32].
• HSF and Msn2/4p can exclusively or cooperatively activate the yeast HSP104 gene [33].
• We show that Hsp104p greatly stimulates the assembly of Sup35p into fibrils, whereas Ydj1p has inhibitory effect [34].
• Overproduction of Hsp104p suppressed the accelerated aging of cells lacking Sir2p, and drugs inhibiting damage segregation further demonstrated that spatial quality control is required to rejuvenate the progeny [35].

Other interactions of HSP104

• Consistent with a role of STREs in the induction of stress resistance, a number of other stress protein genes (e.g. HSP104) are regulated like CTT1 [36].
• Heat-induced activation of the HSP26, HSP104, and SSA4 genes was attenuated in the mutant, indicating dependence on TFIIE for maximal rates of de novo synthesis [37].
• Gene disruptions showed that tps2 and hsp104 null mutants each produced moderate heat shock sensitivity in stationary phase cells [26].
• The results indicate that during the first hours of microvinification there is an increase in the GPDI mRNA levels with a maximum about one hour after inoculation, and a decrease in the amount of HSP12 and HSP104 mRNAs, although with differences between them [38].
• These results indicate that, in addition to trehalose, Hsp104 and the Msn2/4-controlled genes, other factors exist in S. cerevisiae that can, significantly and independently of the known factors, enhance general stress resistance [11].

Analytical, diagnostic and therapeutic context of HSP104

• Furthermore, in Western blots, we observed that sod mutants showed a different pattern of Hsp104p and Hsp26p expression also different from that in their control strain [39].
• As demonstrated by both gel filtration chromatography and by cross-linking studies with glutaraldehyde, Hsp104 forms a homohexameric particle [40].
• Direct evidence for the intracellular localization of Hsp104 in Saccharomyces cerevisiae by immunoelectron microscopy [41].

References