Disease relevance of Hspa8

• Fusion protein of ATPase domain of Hsc70 with TRP2 acting as a tumor vaccine against B16 melanoma [1].
• Upon heat stress, only Hsc70 translocates into the myotube nuclei [2].
• Previously we found that ethanol increases expression of the constitutive 70-kDa heat shock protein (Hsc70) in NG108-15 neuroblastoma x glioma cells [3].
• We compared 4 evolutionary diverse Hsp70s, E. coli DnaK, wheat cytosolic Hsc70, plant chloroplastic CCS1, and human Hsp70, for their ability to prime and augment a primary immune response against herpes simplex virus-1 (HSV1) [4].
• Immunohistochemistry and Western blot analyses showed that endogenous levels of Hsc70 and Hsp70 did not increase significantly in lumbar motor neurons or dorsal root ganglion sensory neurons up to 24 hours after axotomy [5].

High impact information on Hspa8

• We identify a chaperone complex composed of (1) the synaptic vesicle cysteine string protein (CSP), thought to function in neurotransmitter release, (2) the ubiquitous heat-shock protein cognate Hsc70, and (3) the SGT protein containing three tandem tetratricopeptide repeats [6].
• Mechanistic aspects of chaperone cooperation are now emerging from studies on the regulation of certain signal transduction pathways mediated by Hsc70 and Hsp90 in the eukaryotic cytosol [7].
• In contrast, the distribution of Hsp73 in ScN2a cells was not altered by heat shock; the discrete cytoplasmic structures containing Hsp73 were largely resistant to detergent extraction [8].
• Of these interacting chaperones, only Hdj-2 and Hsc70 frequently (Hdj-2 > Hsc70) co-localize with both the aggregates in the cellular model and with the NIs in the brains of HD exon 1 transgenic mice [9].
• Overexpression of Hdj-1 and Hsc70 is also able to protect cell death caused by polyglutamine-expanded tNhtt and their combination proved to be most effective [9].

Chemical compound and disease context of Hspa8

• Neither phenobarbital pretreatment alone nor phenobarbital plus hypoxia treatment induced HSP72 [10].

Biological context of Hspa8

• This study examined the detailed gene expression pattern of three different heat shock proteins (HSPs), Hsc73, Hsj2, and Hsp86, by means of an in situ hybridization method [11].
• In the present study we show that the chaperoning activity of purified Hsp70 and Hsc70 is minimal under reducing conditions and increases in environments that mimic oxidative stress [12].
• We suggest that the association with the Hsc70-containing complex prevents the NLS from the access of the import receptor through the C-terminal region of p53(Val-135) at 37 degrees C, whereas its dissociation at 32 degrees C allows rapid nuclear import [13].
• Regulation of the Dbl proto-oncogene by heat shock cognate protein 70 (Hsc70) [14].
• We suggested that known ethanol actions on cellular protein trafficking may relate to Hsc70 induction because Hsc70 functions as a molecular chaperone [3].

Anatomical context of Hspa8

• In situ expression of heat shock proteins, Hsc73, Hsj2 and Hsp86 in the developing tooth germ of mouse lower first molar [11].
• Immunodepletion of Hsc70 from the reticulocyte lysate caused p53(Val-135) to bind the import receptor [13].
• Immunostaining reveals the co-localization of the molecular chaperones Hsc70 and Hsp90 with the GFP-myosin in the intermediates, but not in the mature myofibrils [15].
• Auxilin is an Hsp40 family protein that catalytically supports the uncoating of clathrin-coated vesicles through recruitment of Hsc70 in an ATP hydrolysis-driven process [16].
• SEB-treated (5 or 100 microg intraperitoneally) mice revealed increased Hsp25 and Hsp72, but not Hsc73, in jejunal lymphocytes and epithelial cells [17].

Associations of Hspa8 with chemical compounds

• Molecular chaperones such as Hsc70 were associated with p53(Val-135) at 37 degrees C but not at 32 degrees C. When the nuclear export was blocked by leptomycin B, only a fraction lacking Hsc70 was specifically accumulated in the nucleus [13].
• Developmental regulation of murine integrin beta 1 subunit- and Hsc73-encoding genes in mammary gland: sequence of a new mouse Hsc73 cDNA [18].
• In cultured mouse NIH 3T3 cells or human HeLa cells, Hsc70 mRNA levels are low under normal conditions, but can be induced 8-fold higher in both lines by treatment with the amino acid analog azetidine [19].
• Hsc70 released kinesin from vesicles in an MgATP-dependent and N-ethylmaleimide-sensitive manner [20].
• Effects of dexamethasone, heat shock, and serum responses on the inhibition of Hsc70 synthesis by antisense RNA in NIH 3T3 cells [21].

Physical interactions of Hspa8

• Dbl is complexed with Hsc70 in transfected cells, as well as in native mouse brain extracts [14].
• Identification of Hsc70 binding sites in mitochondrial aspartate aminotransferase [22].

Regulatory relationships of Hspa8

• The molecular chaperones Hsp90 and Hsc70 are both necessary and sufficient to activate hormone binding by glucocorticoid receptor [23].

Other interactions of Hspa8

• We show in tumor cells that hypericin targets the heat shock protein (Hsp) 90 chaperone but not Hsp70 (Hsc70) to enhanced ubiquitinylation [24].
• This study is the first report in which Hsc73, Hsj2, and Hsp86 were distinctly expressed in the developing tooth germ, thus suggesting these HSPs are related to the development and differentiation of odontogenic cells [11].
• We propose that Hsc70 attenuates Dbl activity by maintaining an inactive conformation in which the amino terminus is "folded over" the catalytic DH-PH domain [14].
• We examined the effect of heat stress on localization of two sHsps, alphaB-crystallin and Hsp25, and of Hsc70, a member of a different class of heat shock proteins (Hsps), in both undifferentiated and differentiated mouse C2C12 cells [2].
• These results suggest that these peptide regions must not only be exposed but still in a flexible extended conformation in the mAAT folding intermediates recognized by Hsc70 [22].

Analytical, diagnostic and therapeutic context of Hspa8

• Structural predictions were confirmed by site-directed mutagenesis of these residues, resulting in loss of binding of BAG1 to Hsc70 in vitro and in cells [25].
• Here, we report that the C-terminus of Hsc70-interacting protein (CHIP) with a U-box domain is an E3 ubiquitin-ligase collaborating with molecular chaperones Hsp90 and Hsc70 [26].
• A partial integrin beta 1 subunit-encoding cDNA (Itg beta 1) and a new heat-shock protein 70-like-encoding cDNA (Hsc73) homologous to rat Hsc73 were cloned by differential display and RT-PCR from mouse mammary gland [18].
• We examined the regulation of the constitutive and stress-induced 70-kD Hsps (Hsc70 and Hsp70, respectively) after sciatic nerve (SN) axotomy in the neonatal mouse [5].
• Flow cytometry detected a significant 1.2-fold increase in Hsp70/Hsc70 accumulation (P < 0.001) in protoplasts, while Western blotting, quantified by image analysis, showed induction under similar conditions but at lower significance (P < 0.05) [27].

References