Disease relevance of HSC82

• Moreover, among 19 monoclonal antibodies raised against hHsp90, nine cross-reacted with yeast Hsc82, and one with human Grp94, but none bound to PgHtpG or E. coli HtpG [1].

High impact information on HSC82

• At a restrictive temperature the prt1-1 mutation, in addition to decreasing global protein synthesis, caused disproportionate decreases of the synthesis of the Ssa1 and Ssa2 members of the hsp70 heat-shock gene family, and of the Hsp82 and Hsc82 heat-shock proteins [2].
• Treatment of extracts from Hsc82-overexpressing cells with Ca(2+)-calmodulin increased the calcineurin activity associated with Cna2 immune complexes [3].
• Hsc82-overexpressing cells appeared similar to calcineurin-defective cells in salt sensitivity and showed reduced levels of calcineurin-dependent gene expression [3].
• Heat shock factor gains access to the yeast HSC82 promoter independently of other sequence-specific factors and antagonizes nucleosomal repression of basal and induced transcription [4].
• Taken together, our results argue that HSF, independent of and dominant among sequence-specific factors binding to the HSC82 upstream region, antagonizes nucleosomal repression and creates an accessible chromatin structure conducive to preinitiation complex assembly and transcriptional activation [4].

Biological context of HSC82

• Thus, HSP82 and HSC82 constitute an essential gene family in yeast cells [5].
• Cells carrying other combinations of the HSP82 and HSC82 mutations grew well at 25 degrees C, but their ability to grow at higher temperatures varied with gene copy number [5].
• Shortening of telomeres was also observed in wild-type cells upon overexpression of HSC82, or of its temperature-inducible homologue, HSP82 [6].
• Furthermore, the hsf1-82 mutation was suppressed by the HSC82 gene on a multicopy plasmid that restored Hsc82 protein to high levels in these cells [7].
• Here we demonstrate that the high-affinity binding site for heat shock transcription factor (HSF) is occupied independently of other cis-regulatory elements and is critically required for preventing nucleosomal assembly over the yeast HSC82 core promoter under both noninducing (basal) and inducing conditions [4].

Associations of HSC82 with chemical compounds

• AhR complexes containing Hsc82 were preferentially sensitive to the effects of low concentrations of the N-terminal inhibitors radicicol and herbimycin A [8].

Physical interactions of HSC82

• Yeast HSC82 that carried point mutations in the middle region causing deficient binding to the N-terminal region could not support the growth of HSP82-depleted cells at an elevated temperature [9].

Regulatory relationships of HSC82

• When expressed at physiological levels in HSF(1-583) cells, the inducible Hsp90 isoform encoded by HSP82 more efficiently suppressed the temperature sensitivity of this strain than the constitutively expressed gene HSC82, suggesting that different functional roles may exist for these chaperones [10].

Other interactions of HSC82

• Overexpression of HSC82 was found to correct the telomeric defect associated with stn1 mutations [6].
• HSE1, suggesting that the 10-fold higher basal transcription of HSC82 stems, at least in part, from a non-HSE-binding factor [11].
• Consistent with this, the half-life of Mal63p is significantly shorter in the hsc82 Delta cpr7 Delta strain (reduced about 6-fold) and modestly affected in the Hsp90-ts strain (reduced about 2-fold) [12].

Analytical, diagnostic and therapeutic context of HSC82

• Two-dimensional gel electrophoresis of total cell proteins revealed that the hsf1-82 cells were specifically defective in the expression of the Hsc82 and Hsp82 proteins [7].

References