Affinage

HSPA1A

Heat shock 70 kDa protein 1A · UniProt P0DMV8

Round 2 corrected
Length
641 aa
Mass
70.1 kDa
Annotated
2026-04-28
130 papers in source corpus 41 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSPA1A is a stress-inducible 70-kDa molecular chaperone that operates through ATP-controlled allosteric cycling between high- and low-affinity substrate-binding states to maintain protein homeostasis under thermal, ischemic, and oxidative stress (PMID:14010456, PMID:19336004). Its transcription is coordinately regulated by HSF-1, NF-Y, NF-κB, and CREB at discrete promoter elements, while post-transcriptionally nucleolin and METTL3-mediated m6A methylation stabilize its mRNA (PMID:24041570, PMID:24442868, PMID:38538596). Beyond canonical chaperoning—including proteasome recruitment to ribosomes during acute stress and maintenance of ubiquitylated nascent protein solubility during thermotolerance via HSPH1/DNAJB1 (PMID:34010456)—HSPA1A suppresses apoptosis by directly binding Apaf-1 to block apoptosome assembly and by antagonizing AIF-mediated chromatin condensation (PMID:10934467, PMID:11533664), stabilizes lysosomal membranes through BMP binding and acid sphingomyelinase activation (a function abolished by oxidation-sensitized calpain cleavage) (PMID:25074941, PMID:20171158), attenuates NF-κB-driven inflammation (PMID:16361353), and mediates cell-type-specific signaling through Wnt/β-catenin and IL-5/eNOS/ERK pathways (PMID:27279016, PMID:28317868). HSPA1A also embeds in the plasma membrane via selective binding to phosphatidylserine and PI(4)P/PI(3)P, connects to the Hsp90 multichaperone system through its C-terminal EEVD motif recognized by Hop, and delivers preproteins to mitochondrial Tom70 for import (PMID:30999671, PMID:35740982, PMID:10786835, PMID:12526792).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1985 High

    Cloning and sequencing of HSPA1A established it as a deeply conserved member of the DnaK/Hsp70 family with a defined HSE-containing promoter, providing the molecular foundation for all subsequent mechanistic work.

    Evidence DNA sequencing and cross-species alignment of the human hsp70 gene

    PMID:3931075

    Open questions at the time
    • No functional assays performed
    • Protein biochemistry not yet addressed
  2. 1993 High

    Saturation mutagenesis of the HSE resolved which nucleotide positions within the NGAAN motif are critical for HSF binding and heat-inducible transcription, defining the cis-regulatory grammar of HSPA1A induction.

    Evidence Point mutagenesis coupled to EMSA and in vivo transcription assays in HeLa cells

    PMID:8463341

    Open questions at the time
    • Other cis-elements (NF-κB, CREB sites) not yet mapped
    • In vivo promoter occupancy not tested
  3. 1999 High

    Identification of CHIP as a TPR-dependent negative regulator of Hsp70's ATPase and substrate-binding cycle revealed the first endogenous brake on chaperone activity.

    Evidence Yeast two-hybrid, GST pulldown domain mapping (aa 540–650), ATPase and luciferase refolding assays

    PMID:10330192

    Open questions at the time
    • Ubiquitin ligase activity of CHIP not yet discovered
    • Structural basis of CHIP–Hsp70 interaction not resolved
  4. 2000 High

    The discovery that Hsp70 directly binds the CARD of Apaf-1 to prevent apoptosome assembly established a concrete anti-apoptotic mechanism at the convergence point of the intrinsic pathway.

    Evidence Co-immunoprecipitation, in vitro binding, and cell-free apoptosis reconstitution

    PMID:10934467

    Open questions at the time
    • Structural details of the Hsp70–Apaf-1 interface unknown
    • In vivo validation in KO animals not yet done
  5. 2001 High

    A parallel anti-death mechanism was uncovered: Hsp70 binds and neutralizes AIF independently of ATP binding, demonstrating that HSPA1A blocks both caspase-dependent and caspase-independent death pathways through distinct molecular contacts.

    Evidence Ligand blot, co-IP, cell-free nuclear condensation assay, overexpression and antisense knockdown

    PMID:11533664

    Open questions at the time
    • Binding site on AIF not mapped
    • Relative contribution of Apaf-1 vs. AIF inhibition in physiological stress not quantified
  6. 2001 High

    Gene knockout in mice proved that HSPA1A is non-redundant for acquired thermotolerance and neuroprotection: Hspa1a−/− mice lost thermotolerance and showed ~56% larger brain infarcts after focal ischemia, establishing essential in vivo cytoprotective functions.

    Evidence Hspa1a KO mice, thermotolerance and apoptosis assays; intraluminal MCAO with infarct volume measurement

    PMID:11713291 PMID:11739994

    Open questions at the time
    • Paralog compensation (Hspa1b) complicates single-KO interpretation
    • Downstream effectors in ischemic protection not identified
  7. 2003 High

    Structural recognition of Hsp70's C-terminal EEVD motif by Hop's TPR1 domain and by mitochondrial Tom70 established how HSPA1A physically integrates into the Hsp90 multichaperone machine and the mitochondrial import pathway.

    Evidence Crystal structures of TPR–peptide complexes; co-IP and in vitro import assays with dominant-negative Tom70

    PMID:10786835 PMID:12526792

    Open questions at the time
    • Full-length Hsp70–Hop complex structure not available
    • Whether HSPA1A vs. HSPA8 shows differential Tom70 affinity not tested
  8. 2003 High

    Double-knockout studies revealed that HSPA1A/HSPA1B are required for late-phase ischemic preconditioning cardioprotection and for maintaining genomic stability under stress, extending the gene's functional scope beyond protein folding.

    Evidence HSP70.1/3 double-KO mice in ischemic preconditioning and cytogenetic/radiosensitivity assays

    PMID:12714332 PMID:14701760

    Open questions at the time
    • Mechanism by which Hsp70 maintains chromosome integrity unknown
    • Which DNA repair pathway is facilitated not determined
  9. 2005 High

    HSPA1A was shown to attenuate NF-κB-driven inflammation: Hsp70.1/3 double-KO mice exhibited exaggerated NF-κB activation, cytokine production, and lung injury during sepsis, placing HSPA1A as an endogenous anti-inflammatory brake.

    Evidence HSP70.1/3 KO mice, cecal ligation/puncture, NF-κB EMSA, cytokine ELISA

    PMID:16361353

    Open questions at the time
    • Direct molecular mechanism of NF-κB inhibition not resolved
    • Whether suppression is via IKK, IκB stabilization, or nuclear factor sequestration unknown
  10. 2010 High

    Calpain-mediated cleavage of Hsp70.1 was found to destabilize lysosomes after ischemia-reperfusion, and oxidative carbonylation was shown to sensitize this cleavage—revealing how post-translational damage converts HSPA1A from a lysosomal stabilizer to a permissive factor for cell death.

    Evidence Monkey hippocampal ischemia model, in vitro μ-calpain cleavage assay with HNE/H2O2 pretreatment, immunofluorescence colocalization

    PMID:20171158

    Open questions at the time
    • Exact calpain cleavage site(s) on Hsp70.1 not identified
    • Whether calpain cleavage occurs in non-neuronal contexts not tested
  11. 2013 High

    Comprehensive promoter dissection identified coordinated regulation by HSF-1, NF-Y, NF-κB, and CREB at mapped binding sites, with stimulus-specific activation routes (heat via HSF-1/NF-Y, TNF-α via NF-κB, cAMP via CREB, ischemia via NF-κB and CREB), resolving how diverse stresses converge on HSPA1A transcription.

    Evidence Promoter-reporter, EMSA, ChIP, and siRNA knockdown of each factor

    PMID:24041570

    Open questions at the time
    • Chromatin remodeling events at the locus not characterized
    • Combinatorial logic among the four factors not quantitatively modeled
  12. 2014 High

    The lysosomal stabilization mechanism was molecularly resolved: intact Hsp70.1 binds BMP at the inner lysosomal leaflet and enhances acid sphingomyelinase activity; calpain cleavage abolishes this interaction, linking chaperone integrity to lysosomal membrane competence.

    Evidence Primate ischemia model, lipid–protein binding assay, ASM activity measurement, lysosomal fractionation

    PMID:25074941

    Open questions at the time
    • Binding stoichiometry and structural basis of BMP recognition not determined
    • Whether ASM enhancement is direct or via membrane remodeling unclear
  13. 2015 High

    Systematic biochemical characterization showed that HSPA1A binds multiple anionic phospholipids and embeds in membranes, with the NBD contributing most to quantitative lipid binding and nucleotide occupancy inhibiting lipid association—establishing that chaperone and lipid-binding functions are allosterically coupled yet structurally separable.

    Evidence Liposome co-sedimentation, domain-deletion constructs, intrinsic fluorescence, high-salt membrane embedding assay

    PMID:26342809 PMID:26476215

    Open questions at the time
    • Lipid-binding site not mapped at residue resolution
    • In vivo relevance of mitochondrial cardiolipin binding not tested
  14. 2019 High

    Plasma membrane localization of HSPA1A was shown to depend on intracellular phosphatidylserine and PI(4)P/PI(3)P via biosensor competition and pharmacological lipid depletion, defining the lipid determinants of its unconventional surface presentation.

    Evidence PS-biosensor (Lact-C2), lipid-biosensor co-transfection, PI4KIIIα inhibitor, rapamycin-inducible phosphatase, cell surface biotinylation

    PMID:30999671 PMID:35740982

    Open questions at the time
    • Trafficking route from ER/cytoplasm to PM not characterized
    • Whether vesicular or non-vesicular transport is involved unknown
  15. 2020 High

    Site-directed mutagenesis (K71A) dissected the interplay between ATPase and lipid-binding activities: the ATPase-null mutant retained PS affinity but exhibited dramatically altered membrane association kinetics, establishing a two-step binding model (initial electrostatic contact then conformational embedding).

    Evidence K71A mutagenesis, SPR lipid-binding kinetics, ATPase assay, refolding assay, CD spectroscopy

    PMID:32825419

    Open questions at the time
    • Structural snapshot of lipid-bound Hsp70 not available
    • Whether the two-step model applies to all anionic lipids not tested
  16. 2021 High

    Quantitative proteomics revealed dual protein quality-control functions during stress: HSPA1A recruits proteasomes to ribosomes during acute heat stress and, together with HSPH1/DNAJB1, maintains ubiquitylated nascent proteins soluble for proteasomal clearance during thermotolerance, unifying its chaperone activity with the ubiquitin–proteasome system.

    Evidence Quantitative proteomics, HSPA1A and HSPH1 deletions, proximity ligation assay, protein solubility assay, mouse esophageal tumor model

    PMID:34010456

    Open questions at the time
    • How HSPA1A physically bridges ribosome and proteasome not structurally resolved
    • Whether this mechanism extends to non-thermal proteotoxic stresses not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the structural basis for HSPA1A's selective lipid interactions and the trafficking pathway to the plasma membrane; (2) how HSPA1A inhibits NF-κB at the molecular level; (3) the mechanism by which HSPA1A maintains chromosomal integrity; and (4) whether its diverse anti-apoptotic, lysosomal, and signaling functions are coordinated or independently regulated in different subcellular compartments.
  • No high-resolution structure of full-length HSPA1A in a lipid-bound or Apaf-1-bound state
  • Mechanism of NF-κB suppression not molecularly defined
  • Compartment-specific regulation of distinct functions unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 6 GO:0044183 protein folding chaperone 4 GO:0098772 molecular function regulator activity 4 GO:0140657 ATP-dependent activity 3
Localization
GO:0005634 nucleus 3 GO:0005764 lysosome 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-8953897 Cellular responses to stimuli 5 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 2
Partners
AIFM1APAF1DNAJB1STAM2STIP1STUB1TOMM70YBX1
Complex memberships
HSPA1A–HSPH1–DNAJB1 disaggregase complexHsp70–Hop–Hsp90 multichaperone complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 The human HSPA1A (hsp70) gene encodes a 69,800 Da protein with an uninterrupted open reading frame of 1986 nucleotides; its predicted amino acid sequence is 73% identical to Drosophila hsp70 and 47% identical to E. coli DnaK, establishing deep evolutionary conservation. The 5' flanking region contains a TATAAA box, a CCAAT motif, and a heat shock element (HSE) sharing homology with Drosophila heat shock gene regulatory sequences. DNA sequencing, sequence comparison Proceedings of the National Academy of Sciences of the United States of America High 3931075
1993 Saturation mutagenesis of the human HSP70.1 gene promoter heat shock element (HSE) revealed that all five positions of the NGAAN motif contribute to heat shock factor (HSF) binding and heat-inducible transcription, with optimal activity at the sequence AGAAC. Outer positions 1 and 5 have strong influence on activity in addition to the conserved central triplet. Saturation point mutagenesis, in vitro HSF binding assay (EMSA), in vivo transcription assay in HeLa cells The Journal of biological chemistry High 8463341
2000 Hsp70 directly binds the caspase recruitment domain (CARD) of Apaf-1 and inhibits apoptosome formation by preventing oligomerization of Apaf-1 and its association with procaspase-9, thereby blocking caspase-9-dependent apoptosis downstream of cytochrome c release. Co-immunoprecipitation, in vitro binding assay, cell-free apoptosis reconstitution Nature cell biology High 10934467
2001 Hsp70 antagonizes apoptosis-inducing factor (AIF): Hsp70 specifically interacts with AIF as shown by ligand blots and co-immunoprecipitation, and overexpression of Hsp70 prevents AIF-induced chromatin condensation of purified nuclei in a cell-free system and protects cells from AIF-targeted extramitochondrial death. The anti-AIF function is independent of the ATP-binding domain of Hsp70, distinguishing it from Apaf-1 inhibition. Ligand blot, co-immunoprecipitation, cell-free nuclear condensation assay, overexpression and antisense knockdown Nature cell biology High 11533664
2001 Genetic knockout of hsp70.1 (Hspa1a) in mice demonstrated that this gene is required for maintenance of acquired thermotolerance and that its absence increases sensitivity to heat stress-induced apoptosis. Single-gene knockouts of hsp70.1 or hsp70.3 showed functional compensation by the intact paralog, but combined loss causes additive defects. Gene targeting (knockout mice), thermotolerance assay, apoptosis assay Molecular and cellular biology High 11713291
2001 Hsp70.1 and Hsp70.3 are both necessary and sufficient to protect mouse embryos from arsenite-induced neural tube defects: antisense knockdown of hsp70-1/3 increased arsenite-induced dysmorphology up to sixfold, while transgenic overexpression of hsp70-1 under a constitutive promoter decreased the incidence of neural tube defects. Antisense oligonucleotide knockdown in cultured mouse embryos, transgene microinjection (gain-of-function) Molecular reproduction and development High 11424214
2001 hsp70.1 knockout increases infarction volume after focal cerebral ischemia in mice: absence of hsp70.1 resulted in ~56% larger infarct volumes, demonstrating a direct neuroprotective role in vivo. Intraluminal middle cerebral artery occlusion in hsp70.1 knockout mice, infarct volume measurement, Northern/Western blot Stroke High 11739994
2003 Hsp70.1 (Hspa1a) and Hsp70.3 are required for late-phase but not early-phase cardioprotection by ischemic preconditioning: HSP70.1/3 double-null mice lost the 43% infarct-size reduction conferred by preconditioning in wild-type mice during the late phase (24 h later), while early-phase preconditioning protection remained intact. HSP70.1/3 double-knockout mice, ischemic preconditioning protocol, infarct size measurement American journal of physiology. Heart and circulatory physiology High 12714332
2003 Hsp70.1/3 double-knockout cells display genomic instability (chromosome end-to-end associations, radioresistant DNA synthesis), increased residual chromosome aberrations after ionizing radiation, enhanced cell killing, and increased oncogenic transformation, demonstrating that Hsp70.1 and Hsp70.3 are required for maintaining genomic stability under stress conditions. Gene-targeted knockout MEFs, cytogenetic analysis, colony survival assay, oncogenic transformation assay Molecular and cellular biology High 14701760
2003 NF-κB transcriptionally upregulates Hsp70.1 (Hspa1a) after permanent coronary occlusion (PO), and Hsp70.1 contributes to NF-κB-dependent cardioprotection after PO; conversely Hsp70.1 is injurious after ischemia/reperfusion, revealing antithetical context-dependent roles paralleling those of NF-κB itself. Microarray analysis, NF-κB knockout mice, hsp70.1 knockout mice, infarct size measurement Journal of molecular and cellular cardiology Medium 21439970
2004 Deletion of hsp70.1 in mice increases cytochrome c release into the cytoplasm and subsequent caspase-3 activation after focal cerebral ischemia, demonstrating that Hsp70.1 normally suppresses the mitochondrial apoptotic pathway in ischemic neurons. hsp70.1 knockout mice, focal ischemia model, Western blot for cytochrome c and activated caspase-3, immunohistochemistry, TUNEL Stroke High 15243143
2003 In rat liver after whole-body hyperthermia, the second heat shock element (HSE-2; −201 to −178) of the HSP70-1 gene is the dominant cis-regulatory element occupied in vivo; flanking NF-κB-like and GC-box elements are simultaneously protected, suggesting that in addition to HSF1, other transcription factors participate in heat-induced HSP70-1 expression. In vivo genomic footprinting (dimethyl sulfate), gel mobility shift assay (EMSA) with anti-HSF1 antibody Journal of biochemistry Medium 8749322
2005 Deletion of HSP70.1/3 gene expression specifically increases NF-κB activation, TNF-α and IL-6 production, and lung injury in a murine sepsis model, demonstrating that Hsp70.1/3 normally attenuates NF-κB-driven inflammation following sepsis. HSP70.1/3 knockout mice, cecal ligation and puncture sepsis model, NF-κB EMSA, ELISA for cytokines, histopathology American journal of physiology. Lung cellular and molecular physiology High 16361353
2008 hsp70.1 deficiency in mice confers nearly complete resistance to experimental autoimmune encephalomyelitis (EAE): hsp70.1−/− mice sensitized with MOG35-55 showed almost no disease, correlated with loss of autoreactive T cell proliferation and IFN-γ production. T cell transfer and antigen presentation assays demonstrated that inducible Hsp70 is required for activation of autoreactive T cells, and hsp70.1−/− CD4+ T cells were more prone to TCR-induced apoptosis. hsp70.1 knockout mice, EAE model, T cell proliferation assay, IFN-γ ELISA, T cell transfer, antigen presentation assay in vitro European journal of immunology High 18581325
2009 Nucleotide (ATP vs. ADP) binding induces conformational changes in human Hsp70.1 (HSPA1A) that alter the relative positions of the nucleotide-binding domain (NBD) and substrate-binding domain (SBD); ATP causes larger quaternary structural rearrangements than ADP, consistent with the allosteric communication underlying substrate binding/release cycling. Analytical ultracentrifugation, dynamic light scattering BMB reports Medium 19336004
2010 After ischemia-reperfusion in the monkey hippocampal CA1, activated μ-calpain co-localizes with Hsp70.1 at the lysosomal membrane, and Hsp70.1 in CA1 tissue is cleaved by μ-calpain in vitro. Carbonylation of Hsp70.1 by HNE or hydrogen peroxide markedly sensitizes it to calpain cleavage, implicating oxidative modification as a prerequisite for calpain-mediated lysosomal destabilization. Immunofluorescence histochemistry, in vitro cleavage assay with recombinant μ-calpain and Western blot, artificial oxidative stress (HNE, H2O2) Biochemical and biophysical research communications High 20171158
2013 Multiple transcription factors coordinately regulate the Hspa1a (Hsp70.3) promoter: HSF-1 binds at −114/−97 bp and −788/−777 bp; NF-Y binds at −73/−58 bp; NF-κB binds at −133/−124 bp; CREB binds at −483/−476 bp. siRNA knockdown of each factor substantially reduced endogenous Hspa1a expression. Heat-shock induction is co-regulated by HSF-1 and NF-Y/NF-κB; TNF-α induces Hspa1a in an NF-κB-dependent manner; forskolin induces it via CREB. Both NF-κB and CREB activate Hspa1a under ischemia-like conditions in cardiac myoblasts. Promoter-reporter assays, EMSA, chromatin immunoprecipitation (ChIP), siRNA knockdown Journal of molecular biology High 24041570
2014 Hsp70.1 stabilizes the lysosomal membrane by binding the endolysosomal lipid bis(monoacylglycero)phosphate (BMP) via its lipid-binding domain, which enhances acid sphingomyelinase (ASM) activity. In the post-ischemic motor cortex, intact Hsp70.1 binds BMP and increases ASM activity promoting lysosomal stability; in the post-ischemic CA1, calpain activation cleaves Hsp70.1, reduces lysosomal membrane localization and BMP levels, decreasing ASM activity and causing lysosomal rupture. Monkey ischemia-reperfusion model, lipid-protein binding assay, ASM activity measurement, lysosomal fractionation, TUNEL assay The Journal of biological chemistry High 25074941
2014 Nucleolin binds directly to the 3' UTR of HSPA1A mRNA and stabilizes it, thereby increasing HSPA1A protein expression during myocardial ischemic preconditioning. Overexpression of nucleolin enhanced H2O2-preconditioning protection in cardiomyocytes, while nucleolin ablation abrogated it; this protection was reversed by HSPA1A antisense oligonucleotides. RNA-protein interaction studies (RIP), reporter gene assay (3' UTR), nucleolin overexpression and siRNA knockdown, in vivo rat ischemic preconditioning model Cardiovascular research High 24442868
2015 HspA1A (HSPA1A) binds multiple anionic phospholipids and embeds in lipid membranes. The nucleotide-binding domain (NBD) contributes more to quantitative lipid binding than the substrate-binding domain (SBD), but full-length protein is required for membrane embedding. Nucleotide binding (ADP/ATP) inhibits lipid binding, while peptide-substrate binding does not affect it. Lipid binding depends on electrostatic forces plus additional molecular forces and is influenced by lipid saturation level. Liposome co-sedimentation, intrinsic fluorescence, high-salt membrane embedding assay, domain-deletion constructs Cell stress & chaperones High 26342809
2015 HspA1A differentially binds anionic lipids (bis-(monoacylglycero)-phosphate, cardiolipin, sulfatide); for cardiolipin and sulfatide, HspA1A embeds in membranes. Both the NBD and SBD bind lipids in a lipid-specific manner, nucleotides reduce lipid binding, and peptide-substrate binding does not affect it. Interaction with mitochondrial cardiolipin may facilitate localized HspA1A function in mitochondria. Liposome co-sedimentation, domain-specific binding assays Biochemical and biophysical research communications Medium 26476215
2015 CaMKIIγ activated by coxsackievirus B3 (CVB3) replication phosphorylates heat shock factor 1 (HSF1) specifically at Ser230, enhancing Hsp70-1 (HSPA1A) transcription. This phosphorylation also translocates HSF1 from cytoplasm to nucleus, blocking ERK1/2-mediated phosphorylation of HSF1 at Ser307 (a negative regulatory site), further amplifying Hsp70-1 upregulation. Hsp70-1 in turn stabilizes CVB3 genomic RNA via the AU-rich element (ARE) in the viral 3' UTR. CaMKIIγ knockdown, site-directed mutagenesis of HSF1 phosphorylation sites, nuclear fractionation, RNA stability assay, CVB3 infection in vitro and in vivo Cellular and molecular life sciences : CMLS High 26361762
2016 HSPA1A overexpression enhances osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by upregulating β-catenin and downregulating DKK1 and SOST (Wnt pathway antagonists); this effect is partly rescued by a Wnt/β-catenin inhibitor. In a rat tibial fracture model, HSPA1A-overexpressing BMSCs improved bone healing. Overexpression in rat BMSCs, alkaline phosphatase activity, mineral deposition, Western blot for β-catenin/DKK1/SOST, Wnt inhibitor rescue, in vivo fracture model Scientific reports Medium 27279016
2017 HSP70-1 (HSPA1A) is required for IL-5-induced angiogenic responses: HSP70-1 siRNA knockdown suppressed IL-5-induced endothelial cell proliferation, migration, tube formation, and eNOS phosphorylation; conversely, HSP70-1 overexpression enhanced these responses. In HSP70-1 knockout mice, IL-5-induced neovascularization was abolished, while VEGF-induced angiogenesis was unaffected by HSP70-1 status. The transcription factor AP-1 drives HSP70-1 expression downstream of ERK and AKT signaling induced by IL-5/IL-5Rα binding. siRNA knockdown, overexpression, HSP70-1 transgenic and knockout mice, neovascularization assay, eNOS phosphorylation (Western blot), AP-1 reporter Scientific reports High 28317868
2019 HspA1A's plasma membrane (PM) localization depends on its selective interaction with intracellular phosphatidylserine (PS): overexpression of the PS-biosensor Lact-C2 (which sequesters PS) greatly reduced heat-induced PM localization of HspA1A, whereas depletion of PI(4,5)P2 had minimal effect. A TopFluor-PS analog co-localized with HspA1A. PM localization increased during recovery from non-apoptotic heat shock. Confocal microscopy, cell surface biotinylation, PS-biosensor (Lact-C2) and PI(4,5)P2-biosensor (PLCδ-PH) co-transfection, fluorescent PS analog co-localization Biomolecules High 30999671
2020 HSPA1A protects epidermal cells from thermal stress by binding STAM2 (via amino acids 395–509) and reducing ESCRT-0 and STAM2 levels. This HspA1A–STAM2 interaction impedes autophagosome–lysosome fusion, abolishing autophagic flux in thermoresistant cells, which significantly reduces thermal cytotoxicity. HSPA1A knockdown/overexpression, co-immunoprecipitation mapping to aa 395–509, ESCRT-0/STAM2 level measurement, autophagy flux assay (LC3-II, p62), mouse epidermal thermoresistance model The Journal of investigative dermatology High 32533962
2020 LNCAROD lncRNA acts as a scaffold that facilitates the protein-protein interaction between HSPA1A and YBX1. This complex prevents proteasomal degradation of YBX1: loss of LNCAROD shortens the half-life of YBX1 protein, and depletion of HSPA1A in LNCAROD-overexpressing cells accelerates proteasomal degradation of YBX1. Neither YBX1 nor HSPA1A knockdown affects LNCAROD levels. Co-immunoprecipitation, protein half-life assay (cycloheximide chase), siRNA knockdown, overexpression Molecular oncology High 32216017
2021 HSPA1A has dual roles in protein quality control: (i) during acute heat stress, HSPA1A promotes recruitment of the 26S proteasome to translating ribosomes, poising cells for rapid degradation and resumption of protein synthesis; (ii) during thermotolerance acquisition, HSPA1A together with the co-chaperone HSPH1 maintains ubiquitylated nascent/newly synthesized proteins in a soluble state for efficient proteasomal clearance. HSPA1A and its co-factors HSPH1 and DNAJB1 are selectively upregulated during thermotolerance. Quantitative proteomics, HSPA1A deletion, HSPH1 deletion, proximity ligation assay for proteasome–ribosome association, protein solubility assay, mouse esophageal tumor model The EMBO journal High 34010456
2020 HspA1A's chaperone (ATPase) activity and lipid-binding activity are functionally dependent but mediated by non-overlapping regions: a K71A ATPase-null mutant binds PS with similar affinity to wild-type but associates three times faster and dissociates 300 times faster from lipid membranes, supporting a two-step binding model involving initial lipid association followed by a conformational change. PS binding does not affect ATPase activity and subtly enhances refolding activity. K71A mutagenesis, surface plasmon resonance/lipid binding kinetics, ATPase assay (inorganic phosphate release), refolding assay, circular dichroism International journal of molecular sciences High 32825419
2022 HSPA1A's plasma membrane localization is regulated by phosphatidylinositol monophosphates: sequestration of PI(4)P (using PI(4)P biosensor) and PI(3)P significantly reduced heat-induced PM localization, while depletion of PI(4)P and PI(4,5)P2 via a rapamycin-inducible phosphatase system confirmed PI(4)P regulation. PAO, GSK-A1 (PI4KIIIα inhibitor), and wortmannin each reduced HSPA1A surface presentation. Confocal microscopy, cell surface biotinylation, lipid-biosensor co-transfection, pharmacological lipid depletion, rapamycin-inducible phosphatase system Biomolecules High 35740982
2013 HSPA1A facilitates nucleotide excision repair after Benzo[a]pyrene (BaP) exposure: overexpression increased DNA repair capacity (DRC) of BPDE-DNA adducts and reduced comet tail moment, while HspA1A knockdown inhibited repair. Mass spectrometry and co-immunoprecipitation identified casein kinase 2 (CK2) as an HspA1A-interacting partner; both proteins co-localized in the nucleus during DNA repair and HspA1A overexpression enhanced CK2 kinase activity. Comet assay, host cell reactivation assay, co-immunoprecipitation, mass spectrometry, confocal microscopy, CK2 kinase activity assay Cell stress & chaperones Medium 23979991
2018 Alcohol-induced HSPA1A in human monocytes selectively suppresses the TLR4-MyD88 signaling pathway (inhibiting TNF-α and IL-6) but does not affect TLR4-TRIF or TLR3-TRIF cytokine responses. Mechanistic analysis showed that inhibition of PP1 (not HspA1A) prevents alcohol-mediated TLR4-TRIF tolerance via the PP1-IRF3 axis. In vivo binge alcohol human volunteer study, in vitro alcohol exposure, siRNA knockdown of HspA1A, cytokine ELISA, IRF3/TBK1 phosphorylation western blot Journal of immunology Medium 29445009
2019 HspA1A interacts directly with TLR2 and TLR4 on neutrophil surfaces (Co-IP/interaction assay) and this interaction mediates cancer-cell-induced activation of neutrophils, including increased reactive oxygen species production. Co-immunoprecipitation/interaction assay, ROS measurement in neutrophils co-cultured with ovarian cancer cells Cell stress & chaperones Medium 22528050
2011 Extracellular HSPA1A promotes hepatocarcinoma cell proliferation and apoptosis-resistance through TLR2 and TLR4 signaling and downstream NF-κB activation; these effects are abolished by NF-κB inhibition. HSPA1A also upregulates TLR4 expression and promotes HMGB1 release from tumor cells. TLR2/TLR4 blocking antibodies, NF-κB inhibition, cell proliferation assay, apoptosis assay with mitomycin C Cancer letters Medium 22115967
2024 METTL3-mediated m6A methylation of Hspa1a mRNA enhances its stability in osteoblasts via YTHDF2 (acting in a stabilizing rather than degrading capacity). Overexpression of METTL3 inhibits osteoblast aging and upregulates Hspa1a expression; this effect depends on YTHDF2. MeRIP-seq confirmed METTL3-dependent m6A modification on Hspa1a mRNA. MeRIP-seq, METTL3 overexpression/knockdown, YTHDF2 knockdown, mRNA stability assay, osteoblast aging assays Cell death discovery Medium 38538596
2016 HSPA1A overexpression in rat neurons after spinal cord injury inhibits apoptosis by suppressing Bax, caspase-9, and cleaved caspase-3 while promoting Bcl-2 expression; this anti-apoptotic effect is mediated through activation of the Wnt/β-catenin signaling pathway, as inhibition of this pathway attenuates the protection. HSPA1A overexpression and knockdown in rat SCI model (in vivo) and H2O2-treated neuronal cells (in vitro), Western blot for apoptotic markers, Wnt/β-catenin pathway inhibitor rescue Experimental neurology Medium 36538982
2017 In differentiated human neuronal cells following thermal stress, HSPA1A targets nuclear speckles (rich in RNA splicing factors) immediately after heat shock and co-localizes with the disaggregation/refolding machine components DNAJA1 and BAG-1 at the granular component of the nucleolus at 1 h post-stress. HSPA1A (but not HSPA6) also co-localizes with DNAJB1 and HSPH1 immediately at nuclear speckles, while HSPA6 exhibits distinct targeting to perispeckles during recovery. YFP-tagged protein stable cell lines, confocal microscopy, FRAP in live human SH-SY5Y neurons Frontiers in neuroscience Medium 28484369
2016 Following thermal stress in human neuronal cells, HSPA1A targets nuclear speckles and the granular component of the nucleolus with distinct FRAP kinetics from HSPA6; HSPA1A associates more transiently with centrioles than HSPA6, and does not localize to perispeckles (transcription sites) during recovery, indicating that HSPA1A and HSPA6 have different functional roles in neuronal stress response. YFP-tagged proteins, live-imaging confocal microscopy, FRAP in differentiated SH-SY5Y neurons Cell stress & chaperones Medium 27527722
2003 The C-terminal heptapeptide of Hsp70 (ending in EEVD) is specifically recognized by the TPR1 domain of the adaptor protein Hop (Hsp70-Hsp90-organizing protein); crystal structures show the peptide in an extended conformation spanning a groove in TPR1, with electrostatic interactions via the EEVD motif (C-terminal Asp acting as a two-carboxylate anchor) and hydrophobic interactions upstream, mediating assembly of the Hsp70-Hsp90 multichaperone complex. Crystal structure of TPR-peptide complexes, peptide binding assays Cell High 10786835
2003 Cytosolic Hsp70 (and Hsp90) dock onto a specialized TPR domain in the mitochondrial outer membrane import receptor Tom70, delivering preproteins for import. The chaperone/Tom70 interaction is required for formation of a productive preprotein/Tom70 complex; disruption of this docking inhibits import of Hsp70-dependent preproteins into mitochondria. Co-immunoprecipitation, in vitro import assay, dominant-negative Tom70 mutant disrupting TPR-chaperone binding Cell High 12526792
1999 CHIP (carboxyl terminus of Hsc70-interacting protein) directly interacts with the C-terminal residues 540–650 of Hsc70/Hsp70 via its tetratricopeptide repeat domain. CHIP inhibits Hsp40-stimulated ATPase activity of Hsc70 and Hsp70, reduces luciferase refolding, and inhibits substrate binding — negatively regulating the forward reaction of the Hsp70 substrate-binding cycle. Yeast two-hybrid, GST pulldown domain mapping, ATPase assay, luciferase refolding assay, co-immunoprecipitation from human skeletal muscle cells Molecular and cellular biology High 10330192

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2013 The role of oxidative stress in Parkinson's disease. Journal of Parkinson's disease 1396 24252804
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2000 Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell 1016 10786835
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2000 Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nature neuroscience 977 10862698
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1985 Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70. Proceedings of the National Academy of Sciences of the United States of America 810 3931075
2002 Directed proteomic analysis of the human nucleolus. Current biology : CB 780 11790298
1999 Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Molecular and cellular biology 766 10330192
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2005 Regulation of LSD1 histone demethylase activity by its associated factors. Molecular cell 733 16140033
2003 Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70. Cell 723 12526792
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2001 Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nature cell biology 694 11533664
2000 Negative regulation of the Apaf-1 apoptosome by Hsp70. Nature cell biology 690 10934467
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2010 Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell 639 20850016
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2010 A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs. Cell 565 20946988
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2006 Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 517 17110338
2004 Genomic instability and enhanced radiosensitivity in Hsp70.1- and Hsp70.3-deficient mice. Molecular and cellular biology 194 14701760
2020 LNCAROD is stabilized by m6A methylation and promotes cancer progression via forming a ternary complex with HSPA1A and YBX1 in head and neck squamous cell carcinoma. Molecular oncology 147 32216017
2001 Insights into regulation and function of the major stress-induced hsp70 molecular chaperone in vivo: analysis of mice with targeted gene disruption of the hsp70.1 or hsp70.3 gene. Molecular and cellular biology 115 11713291
2001 Targeted hsp70.1 disruption increases infarction volume after focal cerebral ischemia in mice. Stroke 100 11739994
2010 Calpain-mediated Hsp70.1 cleavage in hippocampal CA1 neuronal death. Biochemical and biophysical research communications 90 20171158
2002 Targeted disruption of hsp70.1 sensitizes to osmotic stress. EMBO reports 77 12189176
1993 Chromosomal localization of five murine HSP70 gene family members: Hsp70-1, Hsp70-2, Hsp70-3, Hsc70t, and Grp78. Genomics 77 8486356
2009 Circulating heat shock protein 70 (HSPA1A) in normal and pathological pregnancies. Cell stress & chaperones 75 19821156
2012 Hsp70.1 and related lysosomal factors for necrotic neuronal death. Journal of neurochemistry 71 22118687
2020 LncRNA HOTAIR enhances breast cancer radioresistance through facilitating HSPA1A expression via sequestering miR-449b-5p. Thoracic cancer 66 32374522
1994 Scaffold attachment regions stimulate HSP70.1 expression in mouse preimplantation embryos but not in differentiated tissues. Molecular and cellular biology 61 8007971
2004 Effects of hsp70.1 gene knockout on the mitochondrial apoptotic pathway after focal cerebral ischemia. Stroke 60 15243143
2005 Effects of HSP70.1/3 gene knockout on acute respiratory distress syndrome and the inflammatory response following sepsis. American journal of physiology. Lung cellular and molecular physiology 59 16361353
2003 HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts. American journal of physiology. Heart and circulatory physiology 59 12714332
1995 The major histocompatibility complex region marked by HSP70-1 and HSP70-2 variants is associated with clozapine-induced agranulocytosis in two different ethnic groups. Blood 59 7579351
1992 Antibodies and reactive T cells against the malaria heat-shock protein Pf72/Hsp70-1 and derived peptides in individuals continuously exposed to Plasmodium falciparum. Journal of immunology (Baltimore, Md. : 1950) 56 1431109
1998 Inhibition of hsp70-1 and hsp70-3 expression disrupts preimplantation embryogenesis and heightens embryo sensitivity to arsenic. Molecular reproduction and development 51 9820195
2016 Overexpression of HSPA1A enhances the osteogenic differentiation of bone marrow mesenchymal stem cells via activation of the Wnt/β-catenin signaling pathway. Scientific reports 50 27279016
2012 Plasma Hsp72 (HSPA1A) and Hsp27 (HSPB1) expression under heat stress: influence of exercise intensity. Cell stress & chaperones 43 22222935
2010 Extracellular heat shock protein 70 (HSPA1A) and classical vascular risk factors in a general population. Cell stress & chaperones 43 20490736
2009 Functional SNPs in HSPA1A gene predict risk of coronary heart disease. PloS one 43 19333379
2013 Coordinated transcriptional regulation of Hspa1a gene by multiple transcription factors: crucial roles for HSF-1, NF-Y, NF-κB, and CREB. Journal of molecular biology 42 24041570
2011 Differential expression of HSPA1 and HSPA2 proteins in human tissues; tissue microarray-based immunohistochemical study. Histochemistry and cell biology 42 21373891
2011 Extracellular HSPA1A promotes the growth of hepatocarcinoma by augmenting tumor cell proliferation and apoptosis-resistance. Cancer letters 42 22115967
2007 First identification and functional characterization of an immunogenic protein in unculturable haemotrophic Mycoplasmas (Mycoplasma suis HspA1). FEMS immunology and medical microbiology 41 17328755
2003 The allele (A)(-110) in the promoter region of the HSP70-1 gene is unfavorable to longevity in women. Biogerontology 40 14501185
2021 Dual roles of HSP70 chaperone HSPA1 in quality control of nascent and newly synthesized proteins. The EMBO journal 38 34010456
2017 HSP70-1 is required for interleukin-5-induced angiogenic responses through eNOS pathway. Scientific reports 38 28317868
1993 Analysis of heat shock element recognition by saturation mutagenesis of the human HSP70.1 gene promoter. The Journal of biological chemistry 38 8463341
2016 Effects of transport distance, lairage time and stunning efficiency on cortisol, glucose, HSPA1A and how they relate with meat quality in cattle. Meat science 36 26967002
2014 Heat shock protein 70.1 (Hsp70.1) affects neuronal cell fate by regulating lysosomal acid sphingomyelinase. The Journal of biological chemistry 36 25074941
2002 Impaired repair ability of hsp70.1 KO mouse after UVB irradiation. Journal of dermatological science 36 11858953
2013 Promoter variants at AP2 box region of Hsp70.1 affect thermal stress response and milk production traits in Frieswal cross bred cattle. Gene 34 24055724
2011 Identification of a NF-κB cardioprotective gene program: NF-κB regulation of Hsp70.1 contributes to cardioprotection after permanent coronary occlusion. Journal of molecular and cellular cardiology 34 21439970
2004 The septic shock associated HSPA1B1267 polymorphism influences production of HSPA1A and HSPA1B. Intensive care medicine 34 15232679
2009 Hsp70-1 from Plasmodium falciparum: protein stability, domain analysis and chaperone activity. Biophysical chemistry 33 19339102
2015 Biochemical characterization of the interaction between HspA1A and phospholipids. Cell stress & chaperones 32 26342809
2010 HSFs and regulation of Hsp70.1 (Hspa1b) in oocytes and preimplantation embryos: new insights brought by transgenic and knockout mouse models. Cell stress & chaperones 32 21053113
2001 Characterization and regulation of the major histocompatibility complex-encoded proteins Hsp70-Hom and Hsp70-1/2. Cell stress & chaperones 32 11599570
2024 METTL3-mediated m6A modification increases Hspa1a stability to inhibit osteoblast aging. Cell death discovery 31 38538596
2008 A heat shock protein gene (Hsp70.1) is critically involved in the generation of the immune response to myelin antigen. European journal of immunology 31 18581325
2008 Polymorphic analysis of the heat-shock protein 70 gene (HSPA1A) in Ménière's disease. Acta oto-laryngologica 30 19241595
2005 Polymorphisms of heat shock protein 70 gene (HSPA1A, HSPA1B and HSPA1L) and schizophrenia. Neuroscience research 30 15963589
2004 Early transcriptional activation of the hsp70.1 gene by osmotic stress in one-cell embryos of the mouse. Biology of reproduction 30 14766729
2002 Differential heat shock gene hsp70-1 response to toxicants revealed by in vivo study of lungs in transgenic mice. Cell stress & chaperones 30 12653483
2017 Knockdown of Heat Shock Proteins HSPA6 (Hsp70B') and HSPA1A (Hsp70-1) Sensitizes Differentiated Human Neuronal Cells to Cellular Stress. Neurochemical research 29 29090408
2019 Membrane Localization of HspA1A, a Stress Inducible 70-kDa Heat-Shock Protein, Depends on Its Interaction with Intracellular Phosphatidylserine. Biomolecules 28 30999671
2021 Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring. Biomolecules 27 34827586
2019 Functional redundancy of HSPA1, HSPA2 and other HSPA proteins in non-small cell lung carcinoma (NSCLC); an implication for NSCLC treatment. Scientific reports 27 31591429
2015 Increased circulating heat shock protein 70 (HSPA1A) levels in gestational diabetes mellitus: a pilot study. Cell stress & chaperones 27 25720752
2017 Differential Targeting of Hsp70 Heat Shock Proteins HSPA6 and HSPA1A with Components of a Protein Disaggregation/Refolding Machine in Differentiated Human Neuronal Cells following Thermal Stress. Frontiers in neuroscience 24 28484369
2013 HspA1A facilitates DNA repair in human bronchial epithelial cells exposed to Benzo[a]pyrene and interacts with casein kinase 2. Cell stress & chaperones 24 23979991
2012 The interaction of HspA1A with TLR2 and TLR4 in the response of neutrophils induced by ovarian cancer cells in vitro. Cell stress & chaperones 24 22528050
2010 HSPA1A is upregulated in periodontal ligament at early stage of tooth movement in rats. Histochemistry and cell biology 24 20809232
1993 Gametic association of HSP70-1 promoter region alleles and their inclusion in extended HLA haplotypes. Tissue antigens 24 7903489
2020 HSPA1A Protects Cells from Thermal Stress by Impeding ESCRT-0-Mediated Autophagic Flux in Epidermal Thermoresistance. The Journal of investigative dermatology 23 32533962
2013 Stress-induced localization of HSPA6 (HSP70B') and HSPA1A (HSP70-1) proteins to centrioles in human neuronal cells. Cell stress & chaperones 23 24061851
1995 Dominant role of the second heat shock element in expression of the HSP70-1 gene in rat liver after whole body hyperthermia. Journal of biochemistry 23 8749322
2018 Human Binge Alcohol Intake Inhibits TLR4-MyD88 and TLR4-TRIF Responses but Not the TLR3-TRIF Pathway: HspA1A and PP1 Play Selective Regulatory Roles. Journal of immunology (Baltimore, Md. : 1950) 22 29445009
2016 Hsp72 (HSPA1A) Prevents Human Islet Amyloid Polypeptide Aggregation and Toxicity: A New Approach for Type 2 Diabetes Treatment. PloS one 22 26960140
2014 Nucleolin involved in myocardial ischaemic preconditioning via post-transcriptional control of HSPA1A expression. Cardiovascular research 21 24442868
2009 Characterization of nucleotide-induced changes on the quaternary structure of human 70 kDa heat shock protein Hsp70.1 by analytical ultracentrifugation. BMB reports 21 19336004
2004 Association between low self-rated health and heterozygosity for -110A > C polymorphism in the promoter region of HSP70-1 in aged Danish twins. Biogerontology 21 15190186
2021 Targeting HSPA1A in ARID2-deficient lung adenocarcinoma. National science review 20 34858604
2020 Comparative Characterization of Plasmodium falciparum Hsp70-1 Relative to E. coli DnaK Reveals the Functional Specificity of the Parasite Chaperone. Biomolecules 20 32512819
2019 LASP1 promotes proliferation, metastasis, invasion in head and neck squamous cell carcinoma and through direct interaction with HSPA1A. Journal of cellular and molecular medicine 20 31793711
2015 HspA1A, a 70-kDa heat shock protein, differentially interacts with anionic lipids. Biochemical and biophysical research communications 20 26476215
2018 6-OHBDE-47 induces transcriptomic alterations of CYP1A1, XRCC2, HSPA1A, EGR1 genes and trigger apoptosis in HepG2 cells. Toxicology 19 29601929
2012 Genetic variations of HSPA1A, the heat shock protein levels, and risk of atherosclerosis. Cell stress & chaperones 19 22328194
2012 Effects of hyperthermia on Hsp27 (HSPB1), Hsp72 (HSPA1A) and DNA repair proteins hMLH1 and hMSH2 in human colorectal cancer hMLH1-deficient and hMLH1-proficient cell lines. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 19 22515340
2012 Development of rapid and highly sensitive HSPA1A promoter-driven luciferase reporter system for assessing oxidative stress associated with low-dose photodynamic therapy. Cell stress & chaperones 19 23160804
2015 Hsp70-1: upregulation via selective phosphorylation of heat shock factor 1 during coxsackieviral infection and promotion of viral replication via the AU-rich element. Cellular and molecular life sciences : CMLS 18 26361762
2007 Combination of two regulatory elements in the Tetrahymena thermophila HSP70-1 gene controls heat shock activation. Eukaryotic cell 18 18055912
2005 Transactivation of hsp70-1/2 in geldanamycin-treated human non-small cell lung cancer H460 cells: involvement of intracellular calcium and protein kinase C. Journal of cellular biochemistry 18 15696546
2016 Dynamics of the association of heat shock protein HSPA6 (Hsp70B') and HSPA1A (Hsp70-1) with stress-sensitive cytoplasmic and nuclear structures in differentiated human neuronal cells. Cell stress & chaperones 17 27527722
2015 Downhill running and exercise in hot environments increase leukocyte Hsp72 (HSPA1A) and Hsp90α (HSPC1) gene transcripts. Journal of applied physiology (Bethesda, Md. : 1985) 17 25722377
2015 Analysis of serum heat shock protein 70 (HSPA1A) concentrations for diagnosis and disease activity monitoring in patients with rheumatoid arthritis. Cell stress & chaperones 17 25739548
2001 Heat shock proteins Hsp70-1 and Hsp70-3 Are necessary and sufficient to prevent arsenite-induced dysmorphology in mouse embryos. Molecular reproduction and development 17 11424214
2022 HSPA1A ameliorated spinal cord injury in rats by inhibiting apoptosis to exert neuroprotective effects. Experimental neurology 16 36538982
2021 Mutation of GGMP Repeat Segments of Plasmodium falciparum Hsp70-1 Compromises Chaperone Function and Hop Co-Chaperone Binding. International journal of molecular sciences 16 33672387
2023 Exogenous heat shock proteins HSPA1A and HSPB1 regulate TNF-α, IL-1β and IL-10 secretion from monocytic cells. FEBS open bio 15 37583307
2009 Inducible 70 kDa heat shock proteins protect embryos from teratogen-induced exencephaly: Analysis using Hspa1a/a1b knockout mice. Birth defects research. Part A, Clinical and molecular teratology 15 19639652
1995 Immunization with the malaria heat shock like protein hsp70-1 enhances transmission to the mosquito. International immunology 15 7718511
2014 HSPA1A-independent suppression of PARK2 C289G protein aggregation by human small heat shock proteins. Molecular and cellular biology 14 25022755
2012 Development of stable HSPA1A promoter-driven luciferase reporter HepG2 cells for assessing the toxicity of organic pollutants present in air. Cell stress & chaperones 14 22367790
2007 Sequence analysis of HSPA1A and HSPA1B in a multi-ethnic study population. DNA sequence : the journal of DNA sequencing and mapping 14 17364813
2005 Subchronic exposure of hsp70.1-deficient mice to radiofrequency radiation. International journal of radiation biology 14 16449085
2004 Targeted gene disruption of the heat shock protein 72 gene (hsp70.1) in the donor tissue is associated with a prolonged rejection-free survival in the murine skin allograft model. Transplant immunology 14 15589740
2022 The circulating 70 kDa heat shock protein (HSPA1A) level is a potential biomarker for breast carcinoma and its progression. Scientific reports 13 35906272
2020 The effect of whole-body cryostimulation on body composition and leukocyte expression of HSPA1A, HSPB1, and CRP in obese men. Cryobiology 13 32289283
2020 HSPA1A gene polymorphism rs1008438 is associated with susceptibility to acute mountain sickness in Han Chinese individuals. Molecular genetics & genomic medicine 13 32478477
2017 Heart irradiation reduces microvascular density and accumulation of HSPA1 in mice. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 13 29063166
2016 Functional analysis of HSPA1A and HSPA8 in parturition. Biochemical and biophysical research communications 13 28025138
2015 Addition of L-ascorbic acid to culture and vitrification media of IVF porcine blastocysts improves survival and reduces HSPA1A levels of vitrified embryos. Reproduction, fertility, and development 13 25322209
2012 Up-regulation of heat shock protein 70-1 (Hsp70-1) in human limbo-corneal epithelial cells cultivated on amniotic membrane: A proteomic study. Journal of cellular physiology 13 21751214
2023 Hsp70.1 carbonylation induces lysosomal cell death for lifestyle-related diseases. Frontiers in molecular biosciences 12 36819480
2022 Phosphatidylinositol Monophosphates Regulate the Membrane Localization of HSPA1A, a Stress-Inducible 70-kDa Heat Shock Protein. Biomolecules 12 35740982
2017 Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study. PloS one 12 28182740
2020 Characterization of the Relationship between the Chaperone and Lipid-Binding Functions of the 70-kDa Heat-Shock Protein, HspA1A. International journal of molecular sciences 11 32825419
2016 The Brewed Rice Vinegar Kurozu Increases HSPA1A Expression and Ameliorates Cognitive Dysfunction in Aged P8 Mice. PloS one 11 26943920