GRP78 Antibody (OASE00341)
- Known as:
- GRP78 Antibody (OASE00341)
- Catalog number:
- oase00341
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- GRP78 Antibody (OASE00341)
Related genes to: GRP78 Antibody (OASE00341)
- Gene:
- HSPA5 NIH gene
- Name:
- heat shock protein family A (Hsp70) member 5
- Previous symbol:
- GRP78
- Synonyms:
- BiP
- Chromosome:
- 9q33.3
- Locus Type:
- gene with protein product
- Date approved:
- 1991-07-26
- Date modifiied:
- 2015-11-19
Related products to: GRP78 Antibody (OASE00341)
Related articles to: GRP78 Antibody (OASE00341)
- Tumors must adapt to high levels of endoplasmic reticulum (ER) stress to sustain tumor growth and metastases. The chaperone GRP78 (BiP/HSPA5) is a key component of the unfolded protein response (UPR) and essential for ER stress management and adaptive signaling supporting pro-survival UPR activities. Here, we report that oncofetal chondroitin sulfate (CS) glycosaminoglycans are required for ER stress adaptation in osteosarcoma. When osteosarcoma cells encounter ER stress, they upregulate 4-O-sulfated CS at the expense of other glycosaminoglycans leading to a reconfiguration of the glycocalyx in favor of an oncofetal CS subtype. Genetic ablation of the CS synthesis pathway impairs the UPR by preventing osteosarcoma cells from mounting GRP78 expression in response to ER stress. CS deficiency makes osteosarcoma cells hypersensitive to inhibition of GRP78 under both ambient and ER stress conditions, and acute ER stress drives CS-defective osteosarcoma cells into an apoptotic cell death that can be rescued by re-instating CS 4-O-sulfation capacity. This has direct implications for the metastatic progression of osteosarcoma, whereby oncofetal CS protects dissociated osteosarcoma cells from anoikis to allow pulmonary colonization in mice. Our data identify CS glycosaminoglycans as a critical component of the UPR that permits osteosarcoma cells to manage ER stress. - Source: PubMed
Publication date: 2026/08/01
Ørum-Madsen Maj SofiePihl JessicaClausen Thomas MSpliid CharlotteDhez Anne-ChloéZhang Hai-FengChen Yen-HsiVidal-Calvo Elena EthelGustavsson TobiasLizardo MichaelNelepcu IrinaLo JoeyEsko Jeffrey DOo Htoo ZarniDelaidelli AlbertoAgerbæk Mette ØrskovSteinø AnneAl Nakouzi NaderSalanti AliSorensen PoulDaugaard Mads - Intracerebral hemorrhage (ICH) is a devastating neurological disorder characterized by extensive neuronal death, in which ferroptosis has emerged as a central pathological mechanism. Yet, the role of mitophagy in regulating ferroptosis during ICH remains elusive. Herein, we identified a lactylation-mediated HSPA5 (heat shock protein family A (Hsp70) member 5)-VGLL3 (vestigial like family member 3) signaling axis that confers neuroprotection following ICH. We observed a marked upregulation of VGLL3 expression in ICH models, and loss-of-function experiments revealed that VGLL3 silencing exacerbated BNIP3 (BCL2/adenovirus E1B interacting protein 3)-BNIP3L/NIX (BCL2/adenovirus E1B interacting protein 3-like)-mediated, mitophagy-dependent ferroptosis. Mechanistically, VGLL3 enhanced EGLN3 (egl-9 family hypoxia-inducible factor 3) expression and reduced HIF1A/HIF-1α (hypoxia inducible factor 1, alpha subunit) stability, thereby suppressing BNIP3-BNIP3L-driven mitophagy. Upstream, HSPA5 activated VGLL3, and HSPA5 knockdown phenocopied the effects of VGLL3 silencing. Pharmacological activation of HSPA5 with the selective agonist BIP inducer X (BIX) suppressed mitophagy-dependent ferroptosis in cultured neurons, while BIX administration alleviated neuronal death and improved motor function in ICH mice. Epigenetic analyses further demonstrated that HSPA5 expression was transcriptionally modulated by histone H3-Lys18 (H3K18) lactylation, while its non-histone lactylation was catalyzed by the acetyltransferase EP300 (E1A binding protein p300) and removed by the NAD-dependent protein deacetylase SIRT1 (sirtuin 1). Collectively, our findings delineate a lactylation-driven HSPA5-VGLL3-EGLN3-HIF1A/HIF1-1α axis that represses BNIP3-BNIP3L-mediated, mitophagy-dependent ferroptosis. Targeting this pathway may provide a mechanistic rationale and therapeutic strategy for mitigating neuronal injury and functional deficits following ICH. BNIP3: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; EGLN3: egl-9 family hypoxia-inducible factor 3; GPX4: glutathione peroxidase 4; GSH: glutathione; GSSG: oxidized glutathione; HIF1A/HIF-1α: hypoxia inducible factor 1, alpha subunit; HSPA5: heat shock protein family A (Hsp70) member 5; IB: immunoblot; ICH: intracerebral hemorrhage; MDA: malondialdehyde; ROS: reactive oxygen species; SLC7A11: solute carrier family 7 member 11; VGLL3: vestigial like family member 3. - Source: PubMed
Publication date: 2026/09/28
QiXiang ZhangQiKai TangBaoFeng WangYiKui LiuYuXiao MaAoQian XuYuXiao XueSun YuHaoBian LiuGuan - Plexin-B1, Plexin-B2, and Plexin-B3 are members of the Plexin-B receptor family, which engage distinct class IV semaphorins as major ligands: Plexin-B1 binds , Plexin-B2 interacts with and , and Plexin-B3 has been reported to bind HSPA5, while all three may participate in non-redundant ligand-receptor networks. Researchers have found receptors associated with neurological and malignant, immune-mediated, and cardiovascular diseases. However, this study strives to provide a comprehensive, cross-disciplinary synthesis of the context-specific functions of Plexin-B family members and to critically evaluate their emerging therapeutic potential across multiple disease domains. In a tumor- and context-dependent manner, Plexin-B1 and Plexin-B2 promote metastasis in glioblastoma, colorectal cancer, and triple-negative breast cancer (TNBC) through RhoA/Rac1-dependent signaling, while Plexin-B3 exhibits dual roles, acting as a tumor suppressor in TNBC under hypoxic conditions yet promoting motility in pancreatic cancer. Plexin-B regulates neuroinflammation in Alzheimer's disease and T-cell regulation in asthma and other cardiovascular diseases via signals. This review positions the Plexin-B family as a promising yet functionally complex target for future precision medicine. - Source: PubMed
Publication date: 2026/09/14
Xu JianliWang NannanLao JunZhang Renwen - Chinese hamster ovary (CHO) cells are the principal platform for manufacturing recombinant biopharmaceuticals, but sustained production can exceed the protein-folding capacity of the endoplasmic reticulum (ER). Binding immunoglobulin protein (BiP/GRP78), encoded by , is a major ER chaperone that supports folding and modulates unfolded protein response (UPR) signaling, yet increasing BiP abundance has produced beneficial or inhibitory outcomes depending on the recombinant product. Here, we introduced an additional Chinese hamster Hspa5 coding sequence under the constitutive EEF1A1 promoter into a CHO line producing a dulaglutide analogue comprising a modified GLP-1 peptide fused to human IgG4 Fc and compared the resulting stable DUL-BiP population with an empty-vector DUL-Neo control. At constant 37 °C, the two populations showed similar viable cell density and viability trajectories, whereas DUL-BiP cells continued extracellular GLP-1-Fc accumulation for approximately two days after accumulation in DUL-Neo cells had slowed and reached a 40% higher final titer in this experiment. Two independent temperature-shift experiments showed the same direction of the final-titer difference, although the increases were smaller and were accompanied by reduced peak viable cell density. Semi-quantitative immunoblot analysis of samples from the constant-temperature experiment showed a comparatively stable total BiP signal in DUL-BiP cells and a pronounced late increase in DUL-Neo cells, together with temporal changes in cleaved ATF6, eIF2α phosphorylation, and CHOP in both populations. Intracellular GLP-1-Fc did not progressively accumulate. Because the immunoblot time courses were derived from one biological fed-batch experiment, they are interpreted descriptively rather than as independent quantitative biological replicates. Stable constitutive expression of host-derived BiP was therefore associated with prolonged late-stage GLP-1-Fc accumulation in the producer population examined. These kinetics are compatible with a model in which the timing of ER chaperone supply influences the maintenance of productive output, while the underlying mechanism and generality to other producer populations or recombinant products remain to be established. - Source: PubMed
Publication date: 2026/08/28
Shaifutdinov Rolan RKrukov Fedor ASamok Anastasia SVorobiev Ivan IOrlova Nadezhda A - Endoplasmic reticulum stress (ERS) is a significant pathological mechanism in Parkinson's disease (PD), and prolonged ERS can ultimately lead to cellular apoptosis. This study aimed to investigate the neuroprotective effects of Lycium barbarum polysaccharides (LBP) against MPP⁺-induced damage in primary neurons. Mouse primary dopaminergic neurons were treated with MPP⁺ for 24 h to establish PD cell model, and then treated with LBP for another 24 h. Western blot analysis revealed that, compared to the Control group, MPP⁺ treatment induced primary neuron ERS and apoptosis, manifested by upregulating the expression of ERS and apoptotic marker proteins GRP78, p-IRE1α, p-eIF2α, ATF-4, CHOP, Caspase-3 and Bax, repressing mitochondrial transmembrane potential and promoting ROS production, and LBP treatment significantly counteracted MPP-induced ERS and apoptosis. Knockdown of ubiquitin-specific protease 10 (USP10) attenuated the protective effects of LBP in MPP⁺-injured primary neurons. Co-immunoprecipitation (Co-IP) and immunofluorescence co-localization assays confirmed the interaction between USP10 and Yes-associated protein 1 (YAP1). Deubiquitination experiments indicated that USP10 reduced YAP1 ubiquitination and enhanced its protein stability. Additionally, we demonstrated that USP10 suppressed the PERK/eIF2α/ATF-4/CHOP pathway, a key pro-ERS pathway, by inhibiting YAP1 ubiquitination, thereby alleviating MPP⁺-induced ERS and apoptosis. In summary, our findings indicate that LBP attenuates MPP⁺-induced neuronal injury by promoting USP10-mediated deubiquitination of YAP1 and subsequently inhibiting the PERK/eIF2α/ATF-4/CHOP signaling pathway, which proposes a new insight for the pathogenesis research of Parkinson's disease, as well as a potential pharmacological mechanism and target of Lycium barbarum polysaccharides. - Source: PubMed
Publication date: 2026/09/23
Zhang YanMa BonianZuo GuichaoJing ZhengyingDong HuiChen Guisheng