Disease relevance of HSP90B1

• Activation of the grp78 and grp94 promoters by hepatitis C virus E2 envelope protein [1].
• Interestingly, while the majority of the breast cancer cell lines can respond to tunicamycin- and thapsigargin-induced stress by increasing the steady state levels of grp94 and grp78 transcripts, the induction at the GRP protein level is variable and does not always correspond with the transcript level [2].
• We studied the actions of geldanamycin (GA) and herbimycin A (HMA), inhibitors of the chaperone proteins Hsp90 and GRP94, on B chronic lymphocytic leukemia (CLL) cells in vitro [3].
• Recombinant His-tagged Ecgp blocked E. coli invasion efficiently by binding directly to the bacteria [4].
• Three putative hypoxia responsive elements (HRE) were found in the GRP94 promoter [5].

Psychiatry related information on HSP90B1

• Our previous studies have demonstrated that a small number of genes exhibit increased expression in the cerebral cortex of the mouse and rat during recovery sleep after sleep deprivation: egr-3, fra-2, grp78, grp94, ngfi-b, and nr4a3 [6].

High impact information on HSP90B1

• These results indicate that GRP94 is itself a chaperone which acts after BiP [7].
• NH2-terminal sequence and/or Western blot analysis revealed the identity of two of the proteins as the endoplasmic reticulum (ER) resident stress proteins GRP94 and ERp72 [8].
• Biochemical, cell biological and immunological issues surrounding the endoplasmic reticulum chaperone GRP94/gp96 [9].
• Insights into the structural basis of peptide binding to GRP94 have been obtained and the role of the transporter for antigen presentation in defining the GRP94-bound peptide composition has been determined [9].
• gp96 (GRP94) elicits antigen-presenting cell (APC) activation and can direct peptides into the cross- presentation pathways of APC [10].

Chemical compound and disease context of HSP90B1

• Our previous studies have shown that outer membrane protein A (OmpA) of E. coli interacts with a 95-kDa human brain microvascular endothelial cell (HBMEC) glycoprotein, Ecgp, for invasion [4].
• In our study expression of GRP94 was increased in human neuroblastoma SH-SY5Y cells due to exposure to calcium ionophore A23187 [11].

Biological context of HSP90B1

• In vivo, inhibitors of caspases able to block etoposide-induced apoptosis can only partially protect GRP94 from proteolytic cleavage, whereas complete inhibition is observed with calpain inhibitor I but not with the proteasome inhibitor [12].
• We further showed that reduction of GRP94 by antisense decreased cell viability in etoposide-treated Jurkat cells [12].
• We report here that during apoptosis induced by the topoisomerase II inhibitor etoposide, a fraction of GRP94 associated with the endoplasmic reticulum membrane undergoes specific proteolytic cleavage, coinciding with the activation of the caspase CPP32 and initiation of DNA fragmentation [12].
• The 94-kinase can be recovered from ER membrane fractions and is able to phosphorylate both the constitutive and stress-induced forms of GRP94, correlating with their induction kinetics [13].
• Surface plasmon resonance analysis shows that the carboxy-terminal domain of Grp94 (Grp94-CT, residues 518-803) physically interacts with the catalytic subunit of protein kinase CK2 (CK2 alpha) under non-stressed conditions [14].

Anatomical context of HSP90B1

• The endoplasmic reticulum chaperone glycoprotein GRP94 with Ca(2+)-binding and antiapoptotic properties is a novel proteolytic target of calpain during etoposide-induced apoptosis [12].
• Together with the finding that GRP94 was found associated with sialylated apoB, we conclude that correct folding of apoB is dependent on the assistance of molecular chaperone, which play multiple roles in its maturation throughout the secretory pathway including distal compartments such as the trans-Golgi network [15].
• Here we report that a 3- to 5-fold increase in the basal level of the GRP94 protein was observed in all five breast carcinoma cell lines examined [2].
• In carcinoma cells deprived of glucose, mimicking the conditions in poorly vascularized solid tumors, up to 9-fold induction of GRP94 was observed relative to the basal level expressed in a normal breast epithelial cell line [2].
• In contrast, aberrant activation of NFAT and ectopic expression of potential immunogenic proteins (tumor rejection antigen 1 and poliovirus receptor related protein 1) were found in the UC-diseased colon mucosa [16].

Associations of HSP90B1 with chemical compounds

• GRP94 is a 94-kDa chaperone glycoprotein with Ca(2+)-binding properties [12].
• In this report we show that highly purified GRP94 exhibits an active Mg2+-dependent serine kinase activity (termed 94-kinase) [13].
• Regarding the colloidal insoluble multimerized Tg (m-Tg), which bears dityrosine bridges and is present in the follicular lumen, a mild oxidative system generated different soluble forms of Tg, more or less compacted by hydrophobic associations, and linked with Grp78 and Grp94 [17].
• We found that valinomycin prevents UPR-induced protein expression, such as GRP78 and GRP94 [18].
• Expression of GRP94 was found to be increased and HSP27 lowered by the highest concentrations of bifenthrin commercial formulations [19].

Physical interactions of HSP90B1

• Membrane-associated p185erbB2 exists in a stable complex with GRP94 [20].
• Competition experiments of HIF-1 DNA binding using specific probes containing each HRE sequence of the GRP94 promoter clearly evidenced that HIF-1 binds these sequences with high affinity [5].
• Our results demonstrate that GRP94 interacts with FAC both in vitro and in vivo and regulates its intracellular level in a cell culture model [21].
• However, the C-terminal 326 amino acids of GRP94 failed to form a complex with HSP90 alpha [22].

Co-localisations of HSP90B1

• Immunofluorescence staining demonstrated that BAP co-localized with GRP94 in the endoplasmic reticulum [23].

Regulatory relationships of HSP90B1

• Decreased protein and mRNA expression of ER stress proteins GRP78 and GRP94 in HepG2 cells over-expressing CYP2E1 [24].
• AIM: To investigate the expression and significance of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human esophageal carcinoma and adjacent normal tissues [25].
• In order explore possible consequences of GRP94 binding, we have studied recombinant nonmutant thyroglobulin expressed in control Chinese hamster ovary (CHO) cells in comparison to that produced in CHO cells genetically manipulated for selectively increased GRP94 expression [26].

Other interactions of HSP90B1

• This sequence is homologous with previously determined regulatory sequences of the human GRP78 and GRP94 promoters [27].
• The 5'-flanking region of the human calreticulin gene shares homology with the human GRP78, GRP94, and protein disulfide isomerase promoters [27].
• In vitro, GRP94 is not a substrate for CPP32; rather, it can be completely cleaved by calpain, a Ca(2+)-regulated protease [12].
• GA binding to GRP94 disrupts this complex, leading to degradation of pre-existing p185erbB2 protein, and resulting in an altered subcellular distribution of newly synthesized p185erbB2 [20].
• There is no relationship between expression of HSP70, grp94 and cell cycle [28].

Analytical, diagnostic and therapeutic context of HSP90B1

• Northern blot analysis of total RNA from various eukaryotic cells indicates that Ecgp is significantly expressed in HBMECs [4].
• METHODS: The expression of HSP70 and grp94 in 78 human esophageal cancer and adjacent normal tissues was studied by immunohistochemistry and pathology photograph analysis [25].
• Flow cytometry was used to analyze the correlation between expression of HSP70, grp94 and cell cycle in BGC-823 cell line [28].
• METHODS: The expression and localization of HSP70 and grp94 in human gastric carcinoma cell line BGC-823 were determined by immunocytochemistry and indirect immunofluorescence cytochemical staining [28].
• Importantly, co-immunoprecipitation analysis revealed disulfide-linked Tg complexes (previously reported as an early Tg-folding intermediate) especially associated with GRP94 [26].

References