HSPA1A antibody - middle region (ARP33096_T100)
- Known as:
- HSPA1A (anti-) - middle region (ARP33096_T100)
- Catalog number:
- arp33096_t100
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- HSPA1A antibody - middle region (ARP33096_T100)
Related genes to: HSPA1A antibody - middle region (ARP33096_T100)
- Gene:
- HSPA1A NIH gene
- Name:
- heat shock protein family A (Hsp70) member 1A
- Previous symbol:
- HSPA1
- Synonyms:
- HSP70-1
- Chromosome:
- 6p21.33
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-22
- Date modifiied:
- 2016-10-05
Related products to: HSPA1A antibody - middle region (ARP33096_T100)
Related articles to: HSPA1A antibody - middle region (ARP33096_T100)
- To explore the regulatory aspects of mRNAs and miRNAs in suicide, we integrated transcriptomic data from GEO datasets. The analysis of mRNA expression in the prefrontal cortex of suicide victims with major depressive disorder revealed a differential profile with 27 downregulated mRNAs, including , , , , and , which are involved in proteostasis, transcriptional regulation, and apoptosis. Functional enrichment analysis using KEGG and Gene Ontology (GO) revealed significant associations with synaptic plasticity, neuronal survival, and signaling pathways, including MAPK, TGF-β, Wnt, p53, and neurotrophins. Subsequently, using the GSE34120 GEO dataset of miRNAs from the frontal cortex of suicide victims, 105 dysregulated miRNAs were identified. The networks revealed compact regulatory modules with hsa-miR-576-3p, hsa-miR-493, and hsa-miR-550, as well as highly connected central nodes such as hsa-miR-30b, hsa-miR-16a-5p, hsa-miR-181a-5p, and hsa-miR-184. The integration of both profiles allowed the elaboration of miRNA-mRNA regulatory networks in which , , , and interact with multiple dysregulated miRNAs. These findings support the notion that suicide involves complex post-transcriptional dysregulation, particularly related to astrocytic function and neurotrophic signaling, with potential diagnostic and therapeutic applications. - Source: PubMed
Publication date: 2026/03/30
Cortéz-Sánchez José LuisRivera-Escobar Hernán MauricioMuñoz Roa Esther NataliaZabala-Bello Carlos AndrésPérez-Sánchez GilbertoChin Chan José MiguelBautista-Ortiz MonserratLópez-Martínez Karla MaríaOsorio-Antonio FedericoGálvez-Romero José LuisCarrasco Carballo AlanSedeño-Monge VirginiaCastelán FranciscoBautista-Rodríguez Elizabeth - Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by coordinated dysfunction across multiple brain cell types. Natural compounds with multi-target regulatory potential represent promising therapeutic candidates, yet their cell-type-specific mechanisms in the human AD brain remain incompletely understood. In this study, we integrated ligand-based target prediction with large-scale single-nucleus RNA sequencing (snRNA-seq) data from 201,074 nuclei obtained from AD and control human brain samples, together with subcluster-level functional profiling, cell-cell communication analysis, transcriptional regulatory network inference, and structure-based molecular docking and molecular dynamics simulations to systematically characterize the multicellular actions of isofraxidin. Our analyses identified 19 high-confidence isofraxidin targets exhibiting distinct enrichment patterns across AD-associated cell populations. Key targets-including ALOX5 in microglia, MAOB in astrocytes, HSPA1A in endothelial cells (EC), and CBR1 in oligodendrocytes (ODC)-were preferentially localized to disease-relevant cellular subclusters. snRNA-seq revealed marked remodeling of these cell types in AD, characterized by inflammatory microglia, reactive astrocytes, stress-impaired ECs and neurodegeneration-associated ODCs, which overlapped with the highest target enrichment. Functional and regulatory analyses indicated that these vulnerable states converge on oxidative stress, metabolic dysregulation, proteostasis impairment, and aberrant inflammatory signaling. Molecular docking and 100-ns molecular dynamics simulations further confirmed stable and energetically favorable binding of isofraxidin to its core targets. Collectively, this integrative single-cell framework delineates the cell-type-specific therapeutic landscape of isofraxidin in AD and highlights its potential to coordinately modulate key pathogenic pathways underlying neurodegeneration. - Source: PubMed
Publication date: 2026/04/08
Gong XinXu ChengfeiChen XinguiWang Kai - Hsp70 molecular chaperones play a wide array of essential roles in the cell by exploiting their ability to bind incompletely folded client proteins. Our past study of the Hsp70, DnaK, bound to short peptides revealed many details of the interaction between a model substrate and the "pockets" of the canonical binding cleft within the chaperone substrate binding domain (SBD). A major finding was that peptides bound the SBD cleft in either N- to C- or C- to N- orientations with nearly equal frequencies. The current study asks key questions: What determines preferred orientation in the bound substrate? Also, are the binding behaviors observed for DnaK also found for mammalian homologues? Here, we use NMR and cross-linking methods developed in our past study and compare modes of binding to DnaK and the two major human cytoplasmic Hsp70s, Hsc70 and HspA1. Model peptides examined include a "palindromic" peptide, central residue variant peptides, and examples of naturally occurring Hsp70 clients. The results reveal that DnaK is agnostic to backbone orientation of the bound peptide, while Hsc70 modestly favors the C- to N- orientation, and HspA1 strongly favors the N- to C- orientation. Moreover, substrate affinities in general are similar for DnaK and Hsc70 and weaker for HspA1. The binding energy landscapes of these chaperones also differ, as the data suggest deeper energy wells for bound states in DnaK and HspA1 and a more rugged landscape for Hsc70. We speculate that these properties enable the chaperones to perform their physiological functions more effectively. - Source: PubMed
Publication date: 2026/04/06
Bhasne KarishmaDörries LeaMaqtedar AkshithaMager Sydney TClerico Eugenia MGierasch Lila M - Heat shock protein 70 (HSP70) and its E3 ligase co-chaperone CHIP (STUB1) form a critical quality-control complex that directs client proteins toward folding or degradation. Phosphorylation of HSP70 at a conserved threonine in the C-terminal tail influences the fate of clients during cellular stress, yet the structural basis for this regulation remains unclear. Here, we present crystal structures of the CHIP tetratricopeptide repeat (TPR) domain bound to unphosphorylated and phosphorylated HSP70 C-terminal peptides at 1.6-1.9 Å resolution. Phosphate occupancy at Thr636 (HSPA1A numbering) causes steric clashes and electrostatic repulsion within the TPR-binding groove, decreasing affinity by more than 10-fold, as shown by biolayer interferometry and fluorescence polarization. Molecular dynamics simulations confirm destabilization of key hydrogen bonds. A structure-guided G132N substitution in CHIP introduces new hydrogen bonds to the phosphate group, restoring affinity for phosphorylated peptides in isolated TPR domains without losing native ubiquitination activity. However, in full-length CHIP, interface modifications do not restore phosphorylation-impaired stable binding but yield only partial recovery of transient interactions in cells, indicating additional context-dependent constraints on HSP70-CHIP regulation. These findings reveal the atomic mechanism by which phosphorylation impairs HSP70-CHIP interaction during stress and demonstrate that targeted interface engineering can compensate for post-translational changes in isolated domains. Overall, the results explain how cells switch chaperone-mediated triage pathways and offer a framework for understanding how proteostasis becomes dysregulated in neurodegenerative diseases and cancer. - Source: PubMed
Publication date: 2026/03/13
Stewart MariahPaththamperuma ChathuraMcCann ColleenCottingim KelseyZhang HuaqunDelVecchio RianPeng IvyFennimore EricaNix Jay CSaeed Morcos NGeorge KathleenMakaroff KatherineColie MeaganPaulakonis EthanAlmeida Michael FAfolayan Adeleye JBrown Nicholas GPage Richard CSchisler Jonathan C - Cardiovascular disease (CVD) pathogenesis involves multifactorial determinants, including environmental pollutants. This study integrated National Health and Nutrition Examination Survey (NHANES) data and network toxicology approaches to investigate the association and underlying molecular mechanisms between organophosphate flame retardant (OPFR) metabolites and CVD risk. Weighted multivariable logistic regression and restricted cubic splines (RCS) were employed to analyze OPFR metabolites-CVD associations using NHANES data. Protein-protein interaction network, expression quantitative trait locus (eQTL)-based Mendelian randomization (MR), colocalization, and molecular docking analyses pinpointed core pathogenic targets. Mediation analysis assessed potential regulatory roles of 731 immune cell features in core target-CVD pathways. Adjusted regression models revealed significant positive associations between urinary bis (2-chloroethyl) phosphate (BCEP) and dibutyl phosphate (DBP) with CVD risk. RCS analysis demonstrated a linear dose-response relationship for BCEP. HSPA1A was identified as the core OPFR metabolites-CVD mediator, with elevated expression increasing CVD risk. Molecular docking provided supportive evidence for strong binding affinities between HSPA1A and metabolites of OPFR. Crucially, mediation analysis demonstrated that HLA DR on HLA DR CD4 T cells partially mediated the effect of HSPA1A on CVD. These findings provide original insights into associations between emerging organic pollutants and CVD risk and establish a theoretical foundation for targeted prevention and therapy. - Source: PubMed
Publication date: 2026/03/10
Dai KaiHuang YinglanCai HuaxiuZhong GaojunXie ZiqiangWu ShengHuang Donghua