Affinage

Showing HSP90B1 — GRP94 is a alias.

HSP90B1

Endoplasmin · UniProt P14625

Audit flag: ungrounded claim
Length
803 aa
Mass
92.5 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSP90B1 (GRP94/gp96/endoplasmin) is the ER-luminal HSP90 paralog that functions as an ATP-dependent molecular chaperone dedicated to the folding, trafficking, and surface expression of a selective set of secreted and membrane client proteins (PMID:8344253, PMID:19786753, PMID:22642269). It binds and hydrolyzes ATP through N-terminal ATP-binding cassettes, exists as a soluble glycosylated dimer in the ER lumen, and autophosphorylates on serine/threonine residues in a calcium-activated, CK2-sensitive manner (PMID:8344253, PMID:7890776, PMID:9172775). Its conformational cycle is gated by an autoinhibitory pre-N domain that suppresses ATP hydrolysis and is relieved by the Hsp70 co-chaperone BiP, whose nucleotide-binding domain engages the GRP94 middle domain to accelerate ATP-dependent closure into the active chaperone conformation; this relief is promoted by the BiP co-chaperone DnaJB11, and nucleotide binding lowers GRP94's affinity for clients (PMID:35078937, PMID:38483986). Client dissociation is driven by structural maturation of the client rather than by nucleotide hydrolysis per se (PMID:15236592). Through this cycle GRP94 acts as an obligate chaperone for diverse clients including TLRs, integrins, GPIX of the platelet GPIb-IX-V complex, GARP, IGF-II, EGFR, and pro-ADAMTS9, and operates within the ERAD machinery alongside OS-9, Hrd1, and SEL1L to dispose of misfolded substrates such as mutant alpha1-antitrypsin (PMID:18264092, PMID:21576699, PMID:19875450, PMID:19786753, PMID:22642269, PMID:25607841, PMID:34635651). Loss of GRP94 is embryonic lethal and disrupts B-cell integrin compartmentalization, TLR-driven antibody production, Treg GARP/TGF-β function, platelet biogenesis, and zygotic mitosis (PMID:18509083, PMID:21576699, PMID:20520781, PMID:21358806, PMID:25607841). Independently of its luminal role, GRP94 is displayed at the cell surface and released upon necrotic (but not apoptotic) cell death, where it carries antigenic peptides, undergoes receptor-mediated endocytosis into APCs—primarily via scavenger receptor SR-A rather than CD91—for transfer of peptides to MHC class I in a post-ER compartment, and drives dendritic cell maturation and T-cell-dependent immune activation (PMID:8650232, PMID:11248808, PMID:11279246, PMID:11967129, PMID:11970968, PMID:14609958). Surface and membrane gp96 additionally serves as an entry/adherence receptor exploited by pathogens (Listeria Vip, HHV-6 gQ1, pneumococcal oligopeptide permease) and as a pro-tumorigenic partner of HER2, ER-α36, and c-Myc (PMID:16015374, PMID:25546612, PMID:26396174, PMID:32295911, PMID:34061598, PMID:37433010).

Mechanistic history

Synthesis pass · year-by-year structured walk · 37 steps
  1. 1993 High

    Established that gp96/GRP94 is an enzyme with ATP-binding cassettes and Mg2+-dependent ATPase activity that also carries bound peptides, defining it simultaneously as a nucleotide-driven chaperone and a peptide carrier in the ER lumen.

    Evidence In vitro ATPase assay, ATP-binding cassette identification, and acid elution of bound peptides

    PMID:8344253

    Open questions at the time
    • Did not define the conformational cycle linking ATP hydrolysis to client handling
    • Specificity of bound peptides not yet characterized in a defined antigen system
  2. 1994 Medium

    Localized GRP94 as a soluble luminal Ca2+-binding protein subject to CK2 phosphorylation, connecting its activity to ER calcium and post-translational regulation.

    Evidence Subcellular fractionation with SR markers, in vitro CK2 kinase assay, and cDNA cloning

    PMID:8119936

    Open questions at the time
    • Functional consequence of CK2 phosphorylation undefined
    • Phosphorylation shown in vitro, physiological relevance unresolved
  3. 1995 High

    Showed GRP94 autophosphorylates on Ser/Thr in a calcium-activated manner and mapped this activity away from the ATP-binding N-terminal fragment, refining the enzyme's domain architecture.

    Evidence In vitro autophosphorylation with purified protein, limited proteolysis, and ATP-agarose binding

    PMID:7890776

    Open questions at the time
    • Biological role of autophosphorylation not established
    • Whether autophosphorylation occurs in vivo not directly addressed here
  4. 1996 High

    Demonstrated in vivo that gp96 endogenously associates with a defined viral antigenic peptide, validating it as a bona fide peptide carrier rather than an in vitro artifact.

    Evidence Biochemical purification and sequence/MS characterization of gp96-bound VSV peptide from infected cells

    PMID:8650232

    Open questions at the time
    • How peptides load onto gp96 in vivo unresolved
    • Receptor and route for delivery to MHC I not yet defined
  5. 1996 Medium

    Defined the quaternary and luminal nature of GRP94 as a noncovalent dimer with glycosylation-derived heterogeneity, providing the structural basis for later dimerization-dependent chaperone models.

    Evidence Protein purification, native and 2D PAGE, alkali/detergent extraction

    PMID:9172775

    Open questions at the time
    • Functional importance of dimerization not tested here
    • No mapping of the dimer interface
  6. 2000 Medium

    Linked the in vitro CK2 phosphorylation to intact cells, showing only the most heavily glycosylated GRP94 is phosphorylated, implying compartmentalized regulation.

    Evidence Metabolic 32P labeling, tunicamycin treatment, phosphopeptide mapping, in vitro CK2 assay

    PMID:10771098

    Open questions at the time
    • Mechanistic coupling of glycosylation state to phosphorylation unknown
    • Downstream effect on chaperone function untested
  7. 1999 Medium

    Identified that GRP94 is internalized by macrophages through a specific surface receptor into early endosomes, beginning to map the cellular route of extracellular gp96.

    Evidence Fluorescent uptake assay, confocal co-localization, competitive inhibition with mannan and dimethylamiloride

    PMID:10362546

    Open questions at the time
    • Molecular identity of the receptor not established
    • Fate of internalized peptides not traced
  8. 2000 Medium

    Connected surface gp96 to adaptive immune activation by showing it triggers dendritic cell maturation and T-cell-dependent tumor regression, framing gp96 as an immunostimulatory danger signal.

    Evidence Genetic surface targeting of gp96, flow cytometry for DC markers, cytokine ELISA, in vivo tumor regression

    PMID:11739487

    Open questions at the time
    • Receptor mediating DC maturation not identified here
    • Distinction between peptide-dependent and intrinsic adjuvant effects unresolved
  9. 2000 High

    Proposed CD91 as the APC receptor for gp96 mediating peptide re-presentation, offering a first molecular handle on cross-presentation.

    Evidence Direct binding assay, antibody blocking, and alpha2-macroglobulin competition with peptide re-presentation readout

    PMID:11248808

    Open questions at the time
    • Later challenged as the primary receptor
    • Did not exclude additional or alternative receptors
  10. 2001 Medium

    Established that GRP94 is released selectively during necrotic but not apoptotic death and retains antigenic activity, defining the conditions under which gp96 acts as an immune alarm signal.

    Evidence Comparative cell-death assays, ELISA/immunoblot for released GRP94, T-cell hybridoma activation

    PMID:11279246

    Open questions at the time
    • Mechanism of release during necrosis not defined
    • In vivo relevance of released gp96 not tested
  11. 2002 Medium

    Mapped the site of peptide transfer to a post-ER, Rab5a-negative, MHC class I-positive endocytic compartment, refining where gp96-chaperoned antigen enters the presentation pathway.

    Evidence Receptor-mediated endocytosis trafficking with immunofluorescence and kinetic re-presentation under blocked MHC I synthesis

    PMID:11967129

    Open questions at the time
    • Molecular machinery transferring peptide to MHC I unidentified
    • Single-lab compartment assignment
  12. 2002 Medium

    Directly challenged CD91 as the principal gp96 receptor, showing CD91 antagonists do not block uptake or cross-presentation and thereby motivating the search for an alternative receptor.

    Evidence Competitive blocking with alpha2-macroglobulin and receptor-associated protein in uptake and re-presentation assays

    PMID:11970968

    Open questions at the time
    • A negative result that did not itself identify the true receptor
    • Possible cell-type-specific receptor usage not resolved
  13. 2003 High

    Identified scavenger receptor SR-A as the primary receptor for gp96 uptake and peptide re-presentation, resolving the receptor controversy with converging gain-, loss-of-function, and pharmacological evidence.

    Evidence Fucoidan inhibition, SR-A knockout macrophages, ectopic SR-A expression in HEK293, uptake and re-presentation assays

    PMID:14609958

    Open questions at the time
    • Whether SR-A fully accounts for in vivo cross-presentation untested
    • Relative contribution of residual CD91/other receptors not quantified
  14. 2003 High

    Separated genuine gp96 signaling from endotoxin contamination, showing low-endotoxin GRP94 binds LPS but selectively activates ERK without NF-κB/NO induction, clarifying which innate responses are intrinsic to gp96.

    Evidence Depyrogenation, binding assays, NF-κB reporter, NO assay, MAPK Western blots

    PMID:12805368

    Open questions at the time
    • Receptor coupling ERK activation to gp96 not defined
    • Physiological consequence of ERK signaling unaddressed
  15. 2004 High

    Defined the chaperone cycle logic by showing apo-GRP94 undergoes a conformational change suppressed by nucleotide, and that client release depends on client maturation rather than ATP hydrolysis.

    Evidence Conformational change and oligomerization assays, IP of GRP94-Ig heavy chain complexes with ATP/ADP

    PMID:15236592

    Open questions at the time
    • Structural basis of the conformational change not resolved at this stage
    • Role of co-chaperones in the cycle not yet incorporated
  16. 2005 High

    Revealed that pathogens exploit ER/surface gp96, with Listeria Vip using gp96 as an entry receptor, extending gp96 biology to host-pathogen interactions.

    Evidence Far-Western ligand overlay, co-IP, vip mutant infection assays, mouse infection models

    PMID:16015374

    Open questions at the time
    • Surface display mechanism of an ER chaperone not explained
    • Domain of gp96 engaged by Vip not mapped
  17. 2008 High

    Placed GRP94 in the ERAD pathway, showing it associates with OS-9 and acts with Hrd1/SEL1L to degrade mutant alpha1-antitrypsin, expanding its role from folding to quality-control disposal.

    Evidence Co-IP and siRNA knockdown with ERAD substrate degradation assay

    PMID:18264092

    Open questions at the time
    • Whether GRP94 directly recognizes ERAD substrates or acts indirectly unresolved
    • Generality across other ERAD clients untested
  18. 2008 High

    Used a clean conditional knockout to define a selective, non-redundant role for HSP90B1 in B-cell integrin compartmentalization and TLR-driven antibody responses while sparing core Ig assembly.

    Evidence B-cell-specific HSP90B1-null mice, integrin flow cytometry, in vivo immunization assays

    PMID:18509083

    Open questions at the time
    • Did not enumerate the full integrin/TLR client set in B cells
    • Molecular basis of client selectivity not addressed
  19. 2009 High

    Identified GPIX as an obligate gp96 client, with hematopoietic knockout producing a Bernard-Soulier-like phenotype and selective binding to GPIX over other GPIb-IX-V subunits demonstrating client specificity.

    Evidence Hematopoietic conditional KO, flow cytometry, ERAD assay, co-IP with GPIX

    PMID:21576699

    Open questions at the time
    • Structural determinants of GPIX recognition unknown
    • Whether other complex subunits are indirectly affected unresolved
  20. 2009 High

    Showed gp96 chaperones pro-ADAMTS9 for surface trafficking and furin processing, broadening the client repertoire to secreted metalloproteinases.

    Evidence Cross-linking/MS, co-IP, siRNA, cell-surface biotinylation, geldanamycin treatment

    PMID:19875450

    Open questions at the time
    • Direct versus indirect requirement for furin processing not fully separated
    • Binding interface not mapped
  21. 2009 High

    Defined the structural requirement for chaperone function by cross-species rescue with Drosophila gp93 and showed Cys138 disulfide bonding is dispensable, implicating non-covalent N-terminal dimerization in client folding.

    Evidence Ectopic Drosophila gp93 in gp96-deficient cells, client flow cytometry, C138A mutagenesis

    PMID:19786753

    Open questions at the time
    • Dimer interface structure not solved
    • How dimerization couples to client folding unresolved
  22. 2010 Medium

    Demonstrated GRP94 is essential and non-fully-redundant, with knockout causing embryonic lethality, compensatory chaperone upregulation, and altered IRE1/XBP-1 signaling, linking gp96 to UPR homeostasis.

    Evidence Conditional KO mice, GRP94-null ES cells, chaperone Western blots, XBP-1 splicing assay

    PMID:20520781

    Open questions at the time
    • Direct role of GRP94 in IRE1 signaling versus secondary effect unresolved
    • Which clients drive lethality not identified
  23. 2011 Medium

    Revealed a non-redundant role in early development, with oocyte-specific deletion blocking first zygotic mitosis and disrupting spindle-surrounding cytoplasm, where BiP cannot compensate.

    Evidence ZP3-Cre conditional KO, time-lapse microscopy, spindle/ER immunofluorescence

    PMID:21358806

    Open questions at the time
    • Client(s) responsible for the mitotic defect unidentified
    • Mechanism linking ER chaperone to spindle organization unclear
  24. 2012 Medium

    Extended gp96's TLR chaperone role beyond ER egress, showing it remains TLR9-associated during trafficking and maintains TLR9 protease resistance and proteolytic maturation.

    Evidence Pharmacological gp96 inhibition, co-IP during trafficking, protease-sensitivity and signaling assays

    PMID:22554506

    Open questions at the time
    • No genetic KO in this study
    • How gp96 accompanies TLR9 to endosomes mechanistically unresolved
  25. 2012 High

    Validated GRP94 as a selectively druggable target, with a structure-based inhibitor blocking TLR trafficking and IGF-II secretion without affecting cytosolic HSP90 clients.

    Evidence Structure-based inhibitor, trafficking assay, IGF-II ELISA, Drosophila growth and selectivity assays

    PMID:22642269

    Open questions at the time
    • Inhibitor effects on the full client set not surveyed
    • Resistance/selectivity in vivo not characterized here
  26. 2014 High

    Showed GRP94 recognizes on-pathway myocilin aggregates and accelerates aggregation, with inhibition reducing mutant myocilin and rescuing trabecular meshwork toxicity, linking gp96 to a disease-relevant proteostasis decision.

    Evidence In vitro aggregation kinetics, co-precipitation, selective inhibitor cell rescue

    PMID:25027323

    Open questions at the time
    • Why GRP94 promotes rather than prevents aggregation mechanistically unclear
    • In vivo glaucoma relevance not tested here
  27. 2015 High

    Identified GARP as an essential gp96 client in Tregs, linking gp96 to TGF-β activation and FOXP3 stability, and thereby to peripheral immune tolerance.

    Evidence Treg-specific GP96 conditional KO, GARP/integrin flow cytometry, FOXP3 staining, TGF-β activation and adoptive transfer

    PMID:25607841

    Open questions at the time
    • Direct GARP-gp96 binding interface not mapped
    • Whether FOXP3 destabilization is direct or downstream of TGF-β loss unresolved
  28. 2015 Medium

    Defined a surface, C-terminal-domain-mediated interaction of membrane gp96 with HER2 that promotes HER2 dimerization and proliferation, implicating mgp96 in oncogenic receptor signaling.

    Evidence Co-IP, domain mapping, HER2 dimerization (proximity), tumor xenograft, antibody targeting

    PMID:25546612

    Open questions at the time
    • Mechanism of gp96 surface display not addressed
    • Single-lab interaction without independent confirmation
  29. 2015 Medium

    Showed membrane gp96 stabilizes ER-α36 via its C-terminal domain to drive breast cancer growth and invasion, extending the mgp96 oncogenic interactome.

    Evidence Co-IP with domain mapping, siRNA, antibody blocking, in vitro/in vivo tumor assays

    PMID:26396174

    Open questions at the time
    • Direct versus chaperone-mediated stabilization not distinguished
    • Single-lab finding
  30. 2017 High

    Uncovered a cytoskeletal function, showing gp96 binds and regulates NMHCIIA to coordinate plasma membrane bleb dynamics and protect against pore-forming toxins, expanding gp96 beyond ER folding.

    Evidence Reciprocal co-IP, PLA, live-cell bleb imaging, siRNA, zebrafish infection model

    PMID:28039206

    Open questions at the time
    • How an ER chaperone accesses cytoskeletal myosin mechanistically unclear
    • Whether this reflects surface or intracellular gp96 unresolved
  31. 2019 Medium

    Linked GRP94 to PI3K/AKT/mTOR control of muscle differentiation through interaction with Pik3ip1, identifying a signaling-regulatory partner.

    Evidence Co-IP, PLA, Pik3ip1 siRNA epistasis, muscle differentiation assays

    PMID:31025379

    Open questions at the time
    • Whether Pik3ip1 is a folding client or signaling partner unresolved
    • Single-lab interaction
  32. 2020 Medium

    Showed cell-surface gp96 is an entry receptor for HHV-6A/B via interaction with viral gQ1, further establishing gp96 as a pathogen-exploited surface determinant.

    Evidence Co-IP with gQ1, gp96 overexpression/knockdown, virus entry assay

    PMID:32295911

    Open questions at the time
    • Interaction domains not mapped
    • Single-lab gain/loss-of-function
  33. 2021 High

    Defined a chaperone-protective mechanism stabilizing EGFR by blocking FBXL2-mediated ubiquitination, including TKI-resistant mutants, connecting gp96 to NSCLC oncogenesis and a therapeutic vulnerability.

    Evidence Reciprocal co-IP, competition assay, siRNA/overexpression, ubiquitination assay, xenograft

    PMID:34635651

    Open questions at the time
    • Whether stabilization occurs in ER, surface, or both unresolved
    • Generality to other ubiquitin ligases not tested
  34. 2021 High

    Showed surface GP96 induced during influenza infection cooperates with integrin αV to mediate pneumococcal adherence, defining gp96 in viral-bacterial co-infection susceptibility.

    Evidence Surface GP96 immunofluorescence, co-IP with pneumococcal proteins, inhibition/KO infection assays, mouse pneumonia model

    PMID:34061598

    Open questions at the time
    • Mechanism inducing surface GP96 during infection not fully defined
    • Relative roles of GP96 versus integrin αV not separated
  35. 2022 High

    Resolved the co-chaperone mechanism of the GRP94 cycle, showing BiP accelerates GRP94 ATP-dependent closure via its NBD–GRP94 middle-domain contact and stabilizes a high-energy intermediate, with nucleotide reducing client affinity.

    Evidence Single-molecule FRET, reconstituted ATPase and closure assays, domain mutants

    PMID:35078937

    Open questions at the time
    • In vivo requirement for BiP-GRP94 contact for specific clients not addressed here
    • Structural detail of the closed state not solved
  36. 2023 Medium

    Linked HSP90B1 to c-Myc-driven p21 signaling and chemosensitivity, implicating it in bladder cancer cell senescence and cisplatin response.

    Evidence Co-IP, p21 Western blot, siRNA, SA-β-gal staining, cisplatin sensitivity assay

    PMID:37433010

    Open questions at the time
    • Direct versus indirect HSP90B1-c-Myc relationship unresolved
    • Single-lab correlative mechanism
  37. 2024 High

    Defined the autoinhibitory pre-N domain that suppresses GRP94 ATPase and showed DnaJB11 promotes BiP-GRP94 interaction to relieve it, while demonstrating that some clients fold without direct GRP94-BiP contact in vivo.

    Evidence In vitro ATPase, conformational/structural assays, in vivo client folding, domain-deletion mutants

    PMID:38483986

    Open questions at the time
    • Which clients require BiP-GRP94 contact versus those that do not unresolved
    • Full structure of pre-N-mediated autoinhibition not solved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GRP94 achieves client selectivity, how an ER-luminal chaperone is displayed on the cell surface, and how its surface/cytoskeletal/oncogenic roles relate to its luminal chaperone cycle remain unresolved.
  • No structural basis for selective client recognition across TLRs, integrins, GPIX, GARP, EGFR
  • Mechanism translocating gp96 to the cell surface unexplained
  • Relationship between luminal chaperone cycle and surface receptor functions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 4 GO:0140657 ATP-dependent activity 4 GO:0001618 virus receptor activity 3 GO:0016740 transferase activity 2 GO:0016787 hydrolase activity 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 4 GO:0005768 endosome 2 GO:0005576 extracellular region 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-8953897 Cellular responses to stimuli 1
Partners
DNAJB11EGFRGARPGPIXHSPA5/BIPNMHCIIAOS-9PIK3IP1
Complex memberships
GPIb-IX-V complex (chaperones GPIX subunit)Hrd1/SEL1L/OS-9 ERAD machinery

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 gp96/GRP94 contains ATP-binding cassettes, binds ATP, and possesses Mg2+-dependent ATPase activity; gp96 preparations also contain tightly bound peptides elutable by acid extraction, consistent with roles in chaperoning antigenic peptides and facilitating MHC class I–peptide assembly in the ER lumen. In vitro ATPase assay, ATP-binding cassette identification, acid elution of bound peptides The EMBO journal High 8344253
1994 GRP94 resides within cardiac sarcoplasmic reticulum vesicles as a soluble luminal Ca2+-binding protein and is phosphorylated in vitro by casein kinase II at two or more sites near the ends of the molecule. Subcellular fractionation, co-sedimentation with SR markers, in vitro kinase assay, cDNA cloning The Journal of biological chemistry Medium 8119936
1995 Purified GRP94 (grp94/endoplasmin) autophosphorylates itself on serine and threonine residues; autophosphorylation is activated by micromolar calcium, uses both ATP and GTP, and persists in immunoprecipitates and in renatured SDS-PAGE-purified protein; the N-terminal 85 kDa fragment binds ATP-agarose but does not autophosphorylate. In vitro autophosphorylation assay with purified protein, immunoprecipitation, limited proteolysis, ATP-agarose binding The Journal of biological chemistry High 7890776
1996 An immunodominant peptide of vesicular stomatitis virus (VSV N52-59) endogenously associates with gp96 in VSV-infected cells, demonstrating that gp96 acts as a peptide carrier in a well-defined viral model system. Biochemical purification and mass spectrometric/sequence characterization of gp96-bound peptides from infected cells Proceedings of the National Academy of Sciences of the United States of America High 8650232
1996 Purified GRP94 exists as a dimer of noncovalently associated subunits and is a soluble, lumenal protein within the ER; N-linked glycosylation accounts for its molecular weight heterogeneity. Protein purification, native PAGE, 2D non-reducing/reducing PAGE, alkali/detergent extraction Protein expression and purification Medium 9172775
1999 GRP94 undergoes receptor-mediated endocytosis in macrophages via a cell surface receptor distinct from the mannose/fucose receptor; internalized GRP94 co-localizes predominantly with transferrin-positive early endosomes and is not rapidly trafficked to lysosomes. Fluorescent protein uptake assay, subcellular co-localization by confocal microscopy, competitive inhibition with mannan and dimethylamiloride Journal of cell science Medium 10362546
2000 CD91 (alpha2-macroglobulin receptor/LRP) is a cell-surface receptor for gp96 on antigen-presenting cells; CD91 binds gp96 directly (not through another ligand), and anti-CD91 antibodies or the CD91 ligand alpha2-macroglobulin inhibit re-presentation of gp96-chaperoned antigenic peptides. Direct binding assay, antibody blocking of gp96 uptake and peptide re-presentation, competitive inhibition with alpha2-macroglobulin Nature immunology High 11248808
2000 Cell-surface targeting of gp96 on dendritic cells induces their maturation (upregulation of MHC I, MHC II, CD80, CD86, CD40) and secretion of IL-1β, IL-12, and MCP-1; surface-expressed gp96 on tumor cells renders them regressive via a T-lymphocyte-dependent mechanism. Genetic targeting of gp96 to cell surface, flow cytometry for DC maturation markers, cytokine ELISA, in vivo tumor regression assay Journal of immunology Medium 11739487
2001 GRP94 is released into the extracellular space following virally induced or mechanical (freeze/thaw) cell death but not apoptotic cell death; released GRP94 retains antigenicity and elicits ovalbumin-specific T-cell hybridoma activation in a dose-dependent manner. Cell death assays, ELISA/immunoblot for released GRP94, T-cell hybridoma activation assay The Journal of biological chemistry Medium 11279246
2002 Receptor-internalized GRP94 is trafficked to a Rab5a/CD1/transferrin-negative, Fc receptor- and MHC class I-positive endocytic compartment (not the ER); peptide transfer from GRP94 to MHC class I occurs at a post-ER compartment accessed by mature MHC class I molecules. Receptor-mediated endocytosis trafficking assay, immunofluorescence co-localization, kinetic peptide re-presentation assay with 25-D1.16 antibody under conditions of inhibited MHC I synthesis Traffic Medium 11967129
2002 CD91 is not the primary receptor mediating GRP94 cell-surface binding, receptor-mediated endocytosis, or peptide re-presentation in APCs; excess activated alpha2-macroglobulin or receptor-associated protein (pan-CD91 antagonist) did not affect GRP94 uptake or cross-presentation, identifying a CD91-independent pathway. Competitive binding with alpha2-macroglobulin and receptor-associated protein, GRP94 uptake and peptide re-presentation assays in macrophages/dendritic cells Journal of immunology Medium 11970968
2003 Scavenger receptor class-A (SR-A) serves as a primary receptor for gp96 (and calreticulin) recognition and internalization on macrophages and dendritic cells; gp96 internalization and peptide re-presentation are inhibited by the SR-A inhibitor fucoidan, and macrophages from SR-A−/− mice are substantially impaired in gp96 binding and uptake; ectopic SR-A expression in HEK293 cells confers gp96 recognition and uptake activity. Fucoidan inhibition assay, SR-A knockout macrophages, ectopic SR-A expression in HEK293 cells, gp96 uptake and peptide re-presentation assays The EMBO journal High 14609958
2003 Low-endotoxin GRP94/gp96 binds endotoxin in a high-affinity, saturable, and specific manner but does not activate macrophage NF-κB signaling, nitric oxide production, or p38/JNK pathways; low-endotoxin GRP94 does, however, elicit ERK phosphorylation in macrophages at low concentrations. Endotoxin depletion/depyrogenation, binding assays, NF-κB luciferase reporter, nitric oxide assay, Western blot for MAP kinase phosphorylation The Journal of biological chemistry High 12805368
2004 Apo-GRP94 undergoes a time- and temperature-dependent tertiary conformational change that exposes a site of protein-protein interaction; ATP, ADP, and radicicol suppress this conformational change and GRP94 homo-oligomerization; ATP/ADP do not release GRP94 from immunoglobulin heavy chain folding intermediates, indicating that structural maturation of client protein (rather than nucleotide binding/hydrolysis) drives dissociation of GRP94-client complexes. Biochemical conformational change assays, native gel analysis of oligomerization, immunoprecipitation of GRP94-Ig heavy chain complexes with ATP/ADP treatment Biochemistry High 15236592
2000 GRP94 undergoes hyperglycosylation in Sf21 insect cells and is phosphorylated on CK2-sensitive serine/threonine sites in intact cells; only the highest-molecular-weight (most extensively glycosylated) form of GRP94 is phosphorylated in vivo, suggesting compartmentalized regulation. Metabolic 32P labeling, tunicamycin treatment, phosphopeptide mapping, in vitro CK2 phosphorylation Biochimica et biophysica acta Medium 10771098
2005 Listeria monocytogenes virulence factor Vip (an LPXTG surface protein) binds the ER-resident chaperone Gp96 as its cellular receptor; the Vip-Gp96 interaction is critical for bacterial entry into some mammalian cell types. Ligand overlay (far-Western) assay, co-immunoprecipitation, infection assays with vip mutant bacteria, mouse infection models The EMBO journal High 16015374
2008 OS-9, an ER-resident glycoprotein containing a mannose-6-phosphate receptor homology (MRH) domain, associates with the ER chaperone GRP94; together with Hrd1 and SEL1L, GRP94 is required for ERAD of mutant alpha1-antitrypsin. Co-immunoprecipitation, siRNA knockdown of GRP94 with ERAD substrate degradation assay Nature cell biology High 18264092
2008 In B cells, HSP90B1 (gp96/GRP94) is required for proper compartmentalization of B cells via selective integrins and for TLR-stimulated antibody production, but is not required for immunoglobulin assembly, class switching, germinal center formation, or memory antibody responses. B-cell-specific HSP90B1-null mice (conditional knockout), flow cytometry for integrin expression, in vivo immunization/antibody assays, plasma cell differentiation analysis Blood High 18509083
2009 Gp96 (GRP94) is an obligate chaperone for the GPIX subunit of the platelet GPIb-IX-V complex; gp96/grp94 deletion in the murine hematopoietic system leads to thrombocytopenia, prolonged bleeding time, and giant platelets (Bernard-Soulier phenotype); gp96 binds selectively to the GPIX subunit but not to GPIbα or GPIbβ. Hematopoietic-specific gp96 conditional KO, flow cytometry for GPIb-IX complex expression, ERAD assay, co-immunoprecipitation of gp96 with GPIX Blood High 21576699
2009 Gp96 (GRP94) associates with pro-ADAMTS9 in the ER (identified by cross-linking and mass spectrometry) and is required for cell-surface trafficking and furin-mediated processing of pro-ADAMTS9; gp96 siRNA reduces cell-surface pro-ADAMTS9 levels; geldanamycin treatment impairs furin processing of pro-ADAMTS9. Chemical cross-linking, mass spectrometry, co-immunoprecipitation, siRNA knockdown, cell-surface biotinylation assay The Journal of biological chemistry High 19875450
2009 Drosophila gp93 is a functional ortholog of mammalian gp96 and can chaperone murine gp96 clients including integrins α4, αL, β2, TLR2, and TLR9; intermolecular disulfide bond formation via Cys138 of gp96 is not required for chaperone function, implicating non-disulfide-bond-mediated N-terminal dimerization as critical for client protein folding. Ectopic expression of Drosophila gp93 in gp96-deficient mouse cells, flow cytometry for client protein expression, site-directed mutagenesis (C138A) Journal of immunology High 19786753
2010 Complete knockout of GRP94 in embryonic stem cells causes compensatory upregulation of ER chaperones GRP78, calnexin, and calreticulin (but not PDI), and significantly decreases the ER-stress-induced spliced XBP-1 (IRE1 pathway); homozygous GRP94 KO leads to embryonic lethality. Conditional knockout mouse model, GRP94-null embryonic stem cells, Western blot for chaperone levels, XBP-1 splicing assay PloS one Medium 20520781
2011 Oocyte-specific deletion of Hsp90b1 causes failure of first mitosis in mouse zygotes, with abnormal mitotic spindle formation or G2/M block; this is associated with defective organization of the cytoplasmic region surrounding the zygotic spindle; HSPA5 (BiP), although overexpressed, does not compensate for HSP90B1 deficiency in zygotes. ZP3-Cre oocyte-specific conditional KO, time-lapse microscopy, immunofluorescence of mitotic spindle and ER markers PloS one Medium 21358806
2012 Pharmacologic inhibition of gp96 (with a selective inhibitor) inhibits TLR9 proteolytic processing and increases TLR9 sensitivity to proteolytic degradation; TLR9 remains associated with gp96 during intracellular trafficking beyond the ER, suggesting gp96 is required both for TLR9 ER egress and for conformational stability in endosomal compartments. Pharmacological gp96 inhibition, co-immunoprecipitation of gp96-TLR9 during trafficking, protease-sensitivity assay, TLR9 signaling assay Biochemical and biophysical research communications Medium 22554506
2012 A structure-based Grp94-selective inhibitor (compound 2) prevents intracellular trafficking of a TLR (Toll receptor), inhibits secretion of IGF-II, affects the conformation of Grp94, and suppresses Drosophila larval growth (all Grp94-dependent processes), while having no effect on cytosolic Hsp90α/β clients at similar concentrations. Structure-based inhibitor design, cell-based trafficking assay, IGF-II secretion ELISA, Drosophila growth assay, cell viability assay for selectivity Journal of the American Chemical Society High 22642269
2014 In vitro kinetics studies show that Grp94 recognizes on-pathway aggregates (not unfolded monomers) of myocilin olfactomedin domain (myoc-OLF), co-precipitates with myoc-OLF aggregates, and accelerates their aggregation rate; Grp94 inhibition reduces levels of mutant and forced-misfolded wild-type myocilin and rescues toxicity in primary trabecular meshwork cells. In vitro aggregation kinetics, co-precipitation assay, selective Grp94 inhibitor in cell-based rescue assay Human molecular genetics High 25027323
2015 GP96 is an essential chaperone for the cell-surface protein GARP (glycoprotein A repetitions predominant), which is a docking receptor for latent membrane-associated TGF-β; loss of GP96 in Tregs eliminates GARP and integrin surface expression, prevents mLTGF-β expression, impairs active TGF-β production, and destabilizes FOXP3 expression resulting in systemic IFN-γ/IL-17 accumulation. Murine Treg-specific GP96 conditional KO, flow cytometry for GARP and integrin expression, FOXP3 intracellular staining, TGF-β activation assay, in vivo adoptive transfer The Journal of clinical investigation High 25607841
2015 Cell membrane gp96 (mgp96) interacts directly with HER2 at the cell surface via its C-terminal domain, facilitates HER2 dimerization, and promotes cell proliferation; mgp96 levels correlate with HER2 phosphorylation in primary breast tumors; targeting mgp96 with monoclonal antibody decreases cell growth and increases apoptosis. Co-immunoprecipitation, domain-mapping, flow cytometry for HER2 dimerization (FRET/proximity), tumor xenograft assay International journal of cancer Medium 25546612
2015 Cell membrane gp96 (mgp96) C-terminal domain directly interacts with ER-α36 (estrogen receptor variant) on the cell membrane, stabilizing ER-α36 protein and increasing its downstream signaling to promote tumor cell growth and invasion; siRNA or monoclonal antibody targeting mgp96 blocks this interaction and inhibits breast cancer growth in vitro and in vivo. Co-immunoprecipitation with domain mapping, siRNA knockdown, antibody blocking, in vitro/in vivo tumor assays Oncotarget Medium 26396174
2016 Gp96 interacts with non-muscle myosin heavy chain IIA (NMHCIIA), controls its activity and remodeling, and is required for appropriate coordination of plasma membrane bleb formation and retraction in response to pore-forming toxins; Gp96 and NMHCIIA are recruited to PM blebs and protect cells against listeriolysin O during L. monocytogenes infection; this association also affects cytoskeletal organization and cell migration. Co-immunoprecipitation, live-cell imaging of bleb dynamics, siRNA knockdown, in vivo Zebrafish infection model, proximity ligation assay EMBO reports High 28039206
2019 GRP94 interacts with PI3K-interacting protein 1 (Pik3ip1) as determined by co-immunoprecipitation and proximity ligation assay; GRP94 promotes muscle differentiation by inhibiting the PI3K/AKT/mTOR signaling pathway in a Pik3ip1-dependent manner, and regulates Pik3ip1 expression. Co-immunoprecipitation, proximity ligation assay, siRNA knockdown of Pik3ip1, in vitro and in vivo muscle differentiation assays Journal of cellular physiology Medium 31025379
2020 Cell-surface gp96 interacts with viral glycoprotein Q1 (gQ1) of human herpesviruses HHV-6A and HHV-6B during virus entry; gp96 surface expression levels correlate with HHV-6 entry efficiency; loss-of-function and gain-of-function experiments confirm gp96 is required for HHV-6 infection. Co-immunoprecipitation of gp96 with gQ1, gp96 overexpression/knockdown, virus entry assay Journal of virology Medium 32295911
2021 FBXL2 targets EGFR for proteasome-mediated degradation; Grp94 protects EGFR from degradation by blocking FBXL2 binding to EGFR, thereby stabilizing EGFR and promoting NSCLC growth; pharmacologic Grp94 inhibition or FBXL2 upregulation destabilizes EGFR including TKI-resistant mutants. Co-immunoprecipitation, siRNA knockdown, overexpression, ubiquitination assay, tumor xenograft assay Nature communications High 34635651
2021 IAV-infected human epithelial cells display surface GP96 via GP96 chaperone activity; extracellular surface GP96 binds pneumococcal oligopeptide permease components and, together with integrin αV, mediates efficient pneumococcal adherence; GP96 chemical inhibition or genetic knockout reduces pneumococcal adherence and enhances bacterial clearance in infected mice. Immunofluorescence for surface GP96 expression, co-immunoprecipitation of GP96 with pneumococcal proteins, GP96 inhibition/KO infection assays, in vivo mouse pneumonia model mBio High 34061598
2022 BiP (the ER Hsp70) acts as a cochaperone that accelerates Grp94 closure; the BiP nucleotide-binding domain interacts with the Grp94 middle domain; client binding to BiP causes a conformational change that enables BiP to bind Grp94 and accelerate its ATP-dependent closure; single-molecule FRET shows BiP stabilizes a high-energy conformational intermediate of Grp94; together, BiP and ATP push Grp94 into the active closed conformation; nucleotide binding reduces Grp94's affinity for clients. Single-molecule FRET, ATPase activity assay, co-chaperone binding assay, domain mutant analysis, reconstituted in vitro system Proceedings of the National Academy of Sciences of the United States of America High 35078937
2023 HSP90B1 interacts with c-Myc as demonstrated by co-immunoprecipitation; reducing HSP90B1 level reverses p21 overexpression caused by c-Myc overexpression, indicating that HSP90B1/c-Myc interaction regulates the p21 signaling pathway and affects cisplatin chemosensitivity by modulating bladder cancer cell senescence. Co-immunoprecipitation, Western blot for p21, siRNA knockdown, senescence-associated β-galactosidase staining, cisplatin sensitivity assay Aging Medium 37433010
2024 Grp94's pre-N domain suppresses ATP hydrolysis and conformational transitions to the active chaperone conformation; DnaJB11 (BiP co-chaperone) promotes BiP-Grp94 interaction and relieves pre-N domain suppression of Grp94 ATPase activity; ATP binding alters the ATP lid conformation of Grp94; BiP binding stabilizes a partially closed Grp94 intermediate; nucleotide binding reduces Grp94 affinity for clients; folding of some Grp94 clients does not require direct Grp94-BiP interactions in vivo. In vitro ATPase assay, structural studies (conformation assays), in vivo client folding assay, domain deletion mutants, protein interaction assays Proceedings of the National Academy of Sciences of the United States of America High 38483986

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 CD91: a receptor for heat shock protein gp96. Nature immunology 516 11248808
2008 OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD. Nature cell biology 420 18264092
2011 GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum. Biochimica et biophysica acta 335 22079671
1994 The glucose-regulated proteins (GRP78 and GRP94): functions, gene regulation, and applications. Critical reviews in eukaryotic gene expression 304 7987045
2000 The heat shock protein gp96 induces maturation of dendritic cells and down-regulation of its receptor. European journal of immunology 291 10940912
2015 Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. Journal of cellular physiology 259 25546813
1993 Tumor rejection antigen gp96/grp94 is an ATPase: implications for protein folding and antigen presentation. The EMBO journal 246 8344253
2003 Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells. The EMBO journal 193 14609958
2010 GRP94 in ER quality control and stress responses. Seminars in cell & developmental biology 190 20223290
1996 Isolation of an immunodominant viral peptide that is endogenously bound to the stress protein GP96/GRP94. Proceedings of the National Academy of Sciences of the United States of America 169 8650232
1999 GRP94, an ER chaperone with protein and peptide binding properties. Seminars in cell & developmental biology 150 10597632
2005 Gp96 is a receptor for a novel Listeria monocytogenes virulence factor, Vip, a surface protein. The EMBO journal 141 16015374
2005 Roles of heat shock protein gp96 in the ER quality control: redundant or unique function? Molecules and cells 124 16267390
2001 Cell surface targeting of heat shock protein gp96 induces dendritic cell maturation and antitumor immunity. Journal of immunology (Baltimore, Md. : 1950) 120 11739487
2008 Endoplasmic reticulum HSP90b1 (gp96, grp94) optimizes B-cell function via chaperoning integrin and TLR but not immunoglobulin. Blood 117 18509083
1998 Biochemical, cell biological and immunological issues surrounding the endoplasmic reticulum chaperone GRP94/gp96. Current opinion in immunology 114 9523119
2012 Development of a Grp94 inhibitor. Journal of the American Chemical Society 98 22642269
2016 Clients and Oncogenic Roles of Molecular Chaperone gp96/grp94. Current topics in medicinal chemistry 81 27072698
2015 GP96 is a GARP chaperone and controls regulatory T cell functions. The Journal of clinical investigation 80 25607841
2003 GRP94/gp96 elicits ERK activation in murine macrophages. A role for endotoxin contamination in NF-kappa B activation and nitric oxide production. The Journal of biological chemistry 80 12805368
2008 Expression and clinical significance of glucose regulated proteins GRP78 (BiP) and GRP94 (GP96) in human adenocarcinomas of the esophagus. BMC cancer 75 18331622
2002 GRP94 (gp96) and GRP94 N-terminal geldanamycin binding domain elicit tissue nonrestricted tumor suppression. The Journal of experimental medicine 75 12461080
1999 Receptor mediated and fluid phase pathways for internalization of the ER Hsp90 chaperone GRP94 in murine macrophages. Journal of cell science 73 10362546
1995 Autophosphorylation of grp94 (endoplasmin). The Journal of biological chemistry 72 7890776
2012 Proteomic analyses reveal high expression of decorin and endoplasmin (HSP90B1) are associated with breast cancer metastasis and decreased survival. PloS one 71 22363530
2010 Targeted mutation of the mouse Grp94 gene disrupts development and perturbs endoplasmic reticulum stress signaling. PloS one 71 20520781
2002 Cutting edge: CD91-independent cross-presentation of GRP94(gp96)-associated peptides. Journal of immunology (Baltimore, Md. : 1950) 71 11970968
2001 Virally induced lytic cell death elicits the release of immunogenic GRP94/gp96. The Journal of biological chemistry 68 11279246
2002 Hsp90, not Grp94, regulates the intracellular trafficking and stability of nascent ErbB2. Cell stress & chaperones 67 11892991
1994 GRP94 resides within cardiac sarcoplasmic reticulum vesicles and is phosphorylated by casein kinase II. The Journal of biological chemistry 67 8119936
2004 Dendritic cells, T-cell infiltration, and Grp94 expression in cholangiocellular carcinoma. Human pathology 65 15257553
2015 GRP94/gp96 in Cancer: Biology, Structure, Immunology, and Drug Development. Advances in cancer research 63 26916005
2011 Heat-shock protein gp96/grp94 is an essential chaperone for the platelet glycoprotein Ib-IX-V complex. Blood 58 21576699
2000 The heat shock protein gp96: a receptor-targeted cross-priming carrier and activator of dendritic cells. Cell stress & chaperones 58 11189453
2021 Molecular Chaperone GRP94/GP96 in Cancers: Oncogenesis and Therapeutic Target. Frontiers in oncology 56 33898309
2021 FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth. Nature communications 54 34635651
2014 Endoplasmic reticulum heat shock protein gp96 maintains liver homeostasis and promotes hepatocellular carcinogenesis. Journal of hepatology 53 25463537
2002 The heat shock protein Gp96 binds to human neutrophils and monocytes and stimulates effector functions. Blood 53 12446445
1996 Purification and partial molecular characterization of GRP94, an ER resident chaperone. Protein expression and purification 53 9172775
2007 Combination of direct intratumoral administration of dendritic cells and irradiation induces strong systemic antitumor effect mediated by GRP94/gp96 against squamous cell carcinoma in mice. International journal of oncology 52 17671676
2013 Immune chaperone gp96 drives the contributions of macrophages to inflammatory colon tumorigenesis. Cancer research 51 24322981
2010 The anti-myeloma activity of a novel purine scaffold HSP90 inhibitor PU-H71 is via inhibition of both HSP90A and HSP90B1. Journal of hematology & oncology 50 20977755
2015 Cell membrane gp96 facilitates HER2 dimerization and serves as a novel target in breast cancer. International journal of cancer 46 25546612
2005 Increased expression of GRP94 protein is associated with decreased sensitivity to X-rays in cervical cancer cell lines. International journal of radiation biology 46 16368648
2002 Transfer of GRP94(Gp96)-associated peptides onto endosomal MHC class I molecules. Traffic (Copenhagen, Denmark) 46 11967129
2017 Second Generation Grp94-Selective Inhibitors Provide Opportunities for the Inhibition of Metastatic Cancer. Chemistry (Weinheim an der Bergstrasse, Germany) 43 28857290
2004 GRP94 reduces cell death in SH-SY5Y cells perturbated calcium homeostasis. Apoptosis : an international journal on programmed cell death 43 15192333
2001 Enhanced expression of mRNAs of antisecretory factor-1, gp96, DAD1 and CDC34 in human hepatocellular carcinomas. Biochimica et biophysica acta 43 11335099
2019 Long noncoding RNA DLX6-AS1 promotes cell growth and invasiveness in bladder cancer via modulating the miR-223-HSP90B1 axis. Cell cycle (Georgetown, Tex.) 42 31615303
2014 Exploiting the interaction between Grp94 and aggregated myocilin to treat glaucoma. Human molecular genetics 42 25027323
2016 Transformation of the Non-Selective Aminocyclohexanol-Based Hsp90 Inhibitor into a Grp94-Seletive Scaffold. ACS chemical biology 41 27959508
2019 Small molecule grp94 inhibitors block dengue and Zika virus replication. Antiviral research 40 31421166
2011 Overexpression of GRP78 and GRP94 is involved in colorectal carcinogenesis. Histology and histopathology 39 21472681
2004 Adenosine nucleotides and the regulation of GRP94-client protein interactions. Biochemistry 39 15236592
2023 Senescence-related gene c-Myc affects bladder cancer cell senescence by interacting with HSP90B1 to regulate cisplatin sensitivity. Aging 38 37433010
2009 Cell-surface processing of the metalloprotease pro-ADAMTS9 is influenced by the chaperone GRP94/gp96. The Journal of biological chemistry 37 19875450
2004 The messenger and the message: gp96 (GRP94)-peptide interactions in cellular immunity. Cell stress & chaperones 36 15633290
2002 An integrated view of the roles and mechanisms of heat shock protein gp96-peptide complex in eliciting immune response. Frontiers in bioscience : a journal and virtual library 36 11861214
2021 Cell Surface GRP94 as a Novel Emerging Therapeutic Target for Monoclonal Antibody Cancer Therapy. Cells 34 33802964
2020 GRP94 promotes brain metastasis by engaging pro-survival autophagy. Neuro-oncology 33 31637425
2009 Drosophila glycoprotein 93 Is an ortholog of mammalian heat shock protein gp96 (grp94, HSP90b1, HSPC4) and retains disulfide bond-independent chaperone function for TLRs and integrins. Journal of immunology (Baltimore, Md. : 1950) 33 19786553
2017 Resorcinol-Based Grp94-Selective Inhibitors. ACS medicinal chemistry letters 31 29057043
2009 Silencing of GRP94 expression promotes apoptosis in pancreatic cancer cells. International journal of oncology 31 19724918
2023 N6-methyladenosine modification in 18S rRNA promotes tumorigenesis and chemoresistance via HSF4b/HSP90B1/mutant p53 axis. Cell chemical biology 30 36800991
2000 GRP94 hyperglycosylation and phosphorylation in Sf21 cells. Biochimica et biophysica acta 29 10771098
2022 The biology and inhibition of glucose-regulated protein 94/gp96. Medicinal research reviews 28 35861260
2021 GP96 Drives Exacerbation of Secondary Bacterial Pneumonia following Influenza A Virus Infection. mBio 28 34061598
2013 Secreted heat shock protein gp96-Ig: next-generation vaccines for cancer and infectious diseases. Immunologic research 28 24254084
2019 GRP94 promotes muscle differentiation by inhibiting the PI3K/AKT/mTOR signaling pathway. Journal of cellular physiology 27 31025379
2001 Biophysical analysis of the endoplasmic reticulum-resident chaperone/heat shock protein gp96/GRP94 and its complex with peptide antigen. Biochemistry 27 11170476
2011 Oocyte-targeted deletion reveals that hsp90b1 is needed for the completion of first mitosis in mouse zygotes. PloS one 26 21358806
2016 Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins. EMBO reports 25 28039206
2014 Development of radamide analogs as Grp94 inhibitors. Bioorganic & medicinal chemistry 25 25027801
2013 Human α1-Antitrypsin Binds to Heat-Shock Protein gp96 and Protects from Endogenous gp96-Mediated Injury In vivo. Frontiers in immunology 25 24191154
2014 The significance of HSP90AA1, HSP90AB1 and HSP90B1 gene polymorphisms in a Turkish population with non-small cell lung cancer. Anticancer research 24 24511009
2007 Association analysis of HSP90B1 with bipolar disorder. Journal of human genetics 24 17805476
1997 Interleukin-6 upregulates GP96 expression in breast cancer. The Journal of surgical research 24 9202661
2018 Cell entry of a host-targeting protein of oomycetes requires gp96. Nature communications 23 29904064
2018 Toll-like receptor chaperone HSP90B1 and the immune response to Mycobacteria. PloS one 23 30550567
2000 Expression of stress protein gp96, a tumor rejection antigen, in human colorectal cancer. International journal of cancer 23 10797260
2022 The endoplasmic reticulum chaperone BiP is a closure-accelerating cochaperone of Grp94. Proceedings of the National Academy of Sciences of the United States of America 22 35078937
2022 A Pan-Cancer Analysis of Heat-Shock Protein 90 Beta1(HSP90B1) in Human Tumours. Biomolecules 22 36291587
2018 GRP94 Is an Essential Regulator of Pancreatic β-Cell Development, Mass, and Function in Male Mice. Endocrinology 22 29272356
2012 Heat shock protein gp96 regulates Toll-like receptor 9 proteolytic processing and conformational stability. Biochemical and biophysical research communications 22 22554506
2024 Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target. Molecular cancer 21 38243263
2015 Endoplasmic reticulum chaperone gp96 in macrophages is essential for protective immunity during Gram-negative pneumonia. The Journal of pathology 21 26365983
2012 TAT-mediated gp96 transduction to APCs enhances gp96-induced antiviral and antitumor T cell responses. Vaccine 20 23149267
1999 Gp96/GRP94 is a putative high density lipoprotein-binding protein in liver. Biochimica et biophysica acta 20 10101271
2020 GRP94 regulates M1 macrophage polarization and insulin resistance. American journal of physiology. Endocrinology and metabolism 19 32208002
2015 MicroRNA-223 is a novel negative regulator of HSP90B1 in CLL. BMC cancer 19 25880332
2014 Targeted deletion of ER chaperone GRP94 in the liver results in injury, repopulation of GRP94-positive hepatocytes, and spontaneous hepatocellular carcinoma development in aged mice. Neoplasia (New York, N.Y.) 19 25220589
2021 Biological Evaluation of 5'-(N-Ethylcarboxamido)adenosine Analogues as Grp94-Selective Inhibitors. ACS medicinal chemistry letters 18 33738064
2014 Heat shock protein gp96 adjuvant induces T cell responses and cross-protection to a split influenza vaccine. Vaccine 18 24699472
2024 Structural transitions modulate the chaperone activities of Grp94. Proceedings of the National Academy of Sciences of the United States of America 17 38483986
2020 gp96 Is Critical for both Human Herpesvirus 6A (HHV-6A) and HHV-6B Infections. Journal of virology 16 32295911
2015 Chaperone gp96 mediates ER-α36 cell membrane expression. Oncotarget 16 26396174
2008 Secreted heat shock protein gp96-Ig: an innovative vaccine approach. American journal of reproductive immunology (New York, N.Y. : 1989) 16 18405311
2020 Glucose-Regulated Protein 94 (GRP94): A Novel Regulator of Insulin-Like Growth Factor Production. Cells 15 32781621
2012 HSP72 and gp96 in gastroenterological cancers. Clinica chimica acta; international journal of clinical chemistry 15 23266770
2002 The heat shock protein Gp96 links innate and specific immunity. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 15 12537752

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