Affinage

HSPA1A

Heat shock 70 kDa protein 1A · UniProt P0DMV8

Length
641 aa
Mass
70.1 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSPA1A (Hsp70-1) is a stress-inducible molecular chaperone that protects cells against diverse insults — heat, oxidative, osmotic, ischemic, and genotoxic — and governs cell fate through protein quality control, lysosomal integrity, apoptosis suppression, and immune signaling (PMID:11713291, PMID:12189176, PMID:15243143, PMID:34010456). As a protein-quality-control hub, HSPA1A recruits the 26S proteasome to translating ribosomes during acute heat stress and, with co-chaperones HSPH1 and DNAJB1, keeps ubiquitylated nascent proteins soluble for proteasomal clearance during thermotolerance (PMID:34010456); it also suppresses aggregation of amyloidogenic clients such as islet amyloid polypeptide (PMID:26960140). It maintains genomic stability and facilitates DNA repair, with knockout cells showing chromosome aberrations, radioresistant DNA synthesis, and enhanced transformation (PMID:14701760), a repair role linked to direct interaction with and stimulation of casein kinase 2 (PMID:23979991). At the lysosome, HSPA1A binds the anionic lipid bis(monoacylglycero)phosphate (BMP) through its lipid-binding domain to enhance acid sphingomyelinase activity and stabilize the lysosomal membrane; oxidative carbonylation by HNE renders it susceptible to mu-calpain cleavage, and loss of intact HSPA1A precipitates lysosomal rupture and neuronal death (PMID:20171158, PMID:25074941). HSPA1A embeds in anionic phospholipid membranes via its nucleotide-binding domain and translocates to the plasma membrane through selective interaction with phosphatidylserine (PMID:26342809, PMID:30999671). It blocks the mitochondrial apoptotic pathway by limiting cytochrome c release and caspase-3 activation (PMID:15243143) and acts cytoprotectively through Wnt/β-catenin signaling (PMID:36538982). Extracellularly, HSPA1A engages innate-immune receptors TLR2/TLR4 and modulates NF-κB-dependent inflammatory output (PMID:22115967, PMID:29445009). Its transcription is coordinately controlled by HSF-1, NF-Y, NF-κB, and CREB at the promoter, with the heat shock element directing heat-inducible activation (PMID:24041570, PMID:8463341), and its mRNA is post-transcriptionally stabilized by nucleolin and m6A modification (PMID:24442868, PMID:38538596).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2001 High

    Established the core cytoprotective function of HSPA1A by showing it is required for acquired thermotolerance and protection against heat-induced apoptosis, with partial redundancy from Hsp70.3.

    Evidence Single- and double-gene knockout mice with thermotolerance and apoptosis assays

    PMID:11713291

    Open questions at the time
    • Molecular clients protected during thermotolerance not defined here
    • Redundancy with Hsp70.3 complicates gene-specific attribution
  2. 2001 High

    Extended cytoprotection to defined in vivo stress contexts, demonstrating HSPA1A limits ischemic brain injury and prevents arsenite-induced neural tube defects.

    Evidence Knockout mice in middle cerebral artery occlusion; antisense and transgene rescue in cultured embryos

    PMID:11424214 PMID:11739994

    Open questions at the time
    • Downstream protective effectors not yet identified
    • Embryo studies rely on antisense rather than germline knockout
  3. 2002 High

    Revealed stress-selective specialization, showing osmotic stress selectively induces hsp70.1 (not hsp70.3) and that HSPA1A is specifically required for osmotolerance in vitro and in renal medulla in vivo.

    Evidence Gene-specific knockout mice; osmotic stress viability and renal apoptosis assays

    PMID:12189176

    Open questions at the time
    • Mechanism of stress-specific promoter selectivity not resolved
    • Osmoprotective clients unidentified
  4. 2004 High

    Defined the anti-apoptotic mechanism, placing HSPA1A upstream of the mitochondrial pathway by showing its loss increases cytochrome c release and caspase-3 activation after ischemia.

    Evidence Knockout mice in focal ischemia; cytochrome c/caspase-3 immunoblotting and TUNEL

    PMID:15243143

    Open questions at the time
    • Direct molecular target on the mitochondrial pathway not identified
    • Whether effect is chaperone-dependent unclear
  5. 2004 High

    Established a genome-protective role, demonstrating HSPA1A is essential for DNA damage repair and suppression of chromosome instability and oncogenic transformation.

    Evidence Knockout MEFs with irradiation, chromosome aberration, and transformation assays

    PMID:14701760

    Open questions at the time
    • Repair pathway and molecular partners not defined in this study
    • Mechanism connecting chaperone activity to repair unknown
  6. 2005 High

    Linked HSPA1A to innate-immune restraint, showing it suppresses NF-κB activation and inflammatory cytokine output during sepsis.

    Evidence Knockout mice in cecal ligation/puncture; NF-κB EMSA, cytokine ELISA, survival

    PMID:16361353

    Open questions at the time
    • Direct molecular target in the NF-κB pathway not defined
    • Intracellular vs extracellular site of action unresolved
  7. 2010 High

    Identified a degradative regulatory event, showing oxidative carbonylation primes HSPA1A for mu-calpain cleavage at the lysosomal membrane, driving lysosomal rupture and neuronal necrosis.

    Evidence In vitro calpain cleavage assay; HNE/H2O2 carbonylation; in vivo colocalization

    PMID:20171158

    Open questions at the time
    • Cleavage site not precisely mapped
    • Generality across cell types not yet tested at this stage
  8. 2014 High

    Explained the lysosome-protective mechanism, showing HSPA1A binds the lipid BMP to enhance acid sphingomyelinase activity and stabilize lysosomes, with cleavage abolishing this protection.

    Evidence Hsp70.1-BMP binding and ASM activity assays; post-ischemic monkey neuron comparison

    PMID:25074941

    Open questions at the time
    • Structural basis of lipid-binding domain not resolved
    • Quantitative threshold for lysosomal failure undefined
  9. 2015 High

    Characterized the biophysics of membrane interaction, establishing that HSPA1A embeds in anionic phospholipid membranes via its NBD with nucleotide-dependent regulation.

    Evidence Liposome-binding and domain-dissection assays with nucleotide competition

    PMID:26342809 PMID:26476215

    Open questions at the time
    • In vivo relevance of in vitro lipid preferences not tested
    • Membrane topology of embedded protein unknown
  10. 2019 High

    Defined the determinant of surface display, showing HSPA1A plasma membrane localization depends on selective interaction with phosphatidylserine.

    Evidence Confocal microscopy, biotinylation, and PS/PI(4,5)P2 biosensor manipulation

    PMID:30999671

    Open questions at the time
    • Translocation machinery exporting HSPA1A to the surface unknown
    • Functional consequence of PS-dependent display not directly tested here
  11. 2021 High

    Resolved the dual protein-quality-control mechanism, showing HSPA1A recruits the proteasome to ribosomes during acute stress and, with HSPH1/DNAJB1, keeps ubiquitylated nascent proteins soluble during thermotolerance.

    Evidence Quantitative proteomics, deletion/reconstitution, ribosome-proteasome co-fractionation, in vivo tumor model

    PMID:34010456

    Open questions at the time
    • Mechanism of proteasome recruitment to ribosomes not structurally defined
    • Client selectivity not fully mapped
  12. 2013 High

    Mapped the transcriptional control architecture, defining coordinate HSF-1, NF-Y, NF-κB, and CREB binding sites that integrate heat, inflammatory, and cAMP signals at the HSPA1A promoter.

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

    PMID:24041570 PMID:8463341

    Open questions at the time
    • Chromatin/cofactor context in vivo not resolved
    • Combinatorial logic among factors under specific stresses incompletely defined
  13. 2013 Medium

    Provided a molecular partner for the genome-protective role, showing HSPA1A directly interacts with and stimulates casein kinase 2 during DNA repair.

    Evidence Co-IP, mass spectrometry, colocalization, and CK2 kinase activity assay after benzo[a]pyrene

    PMID:23979991

    Open questions at the time
    • Single-lab Co-IP without reciprocal validation
    • How CK2 stimulation drives repair not mechanistically linked
  14. 2018 Medium

    Refined the extracellular/innate-immune role, demonstrating HSPA1A engages TLR2/TLR4 and selectively modulates the TLR4-MyD88 versus TLR4-TRIF branches.

    Evidence Receptor-blocking and siRNA knockdown in monocytes/macrophages with cytokine readouts; in vivo alcohol exposure

    PMID:22115967 PMID:22528050 PMID:29445009 PMID:37583307

    Open questions at the time
    • Direct binding stoichiometry to TLRs/CD14/CD36/CD11b not biochemically resolved
    • Contribution of endotoxin contamination addressed only by controls
  15. 2020 Medium

    Connected HSPA1A to autophagy and to chaperoning of oncogenic clients, showing it binds STAM2 to impede autophagosome-lysosome fusion and stabilizes clients including LASP1 and YBX1.

    Evidence Co-IP with domain mapping, autophagy flux assays, protein half-life and proteasome inhibitor experiments

    PMID:31793711 PMID:32216017 PMID:32533962

    Open questions at the time
    • Single-lab interactions lacking reciprocal validation
    • Whether client stabilization reflects canonical chaperone cycle untested
  16. 2022 Medium

    Established a signaling output for cytoprotection, showing HSPA1A activates Wnt/β-catenin to suppress apoptosis and promote osteogenic differentiation.

    Evidence Gain/loss of function with Wnt inhibitor rescue in SCI and BMSC models

    PMID:27279016 PMID:36538982

    Open questions at the time
    • Direct molecular link between HSPA1A and Wnt components not defined
    • Single-lab models
  17. 2024 Medium

    Extended post-transcriptional control, showing nucleolin and METTL3/YTHDF2-mediated m6A modification stabilize HSPA1A mRNA in cardiac and osteoblast contexts.

    Evidence RNA-protein interaction, reporter assays, MeRIP-seq, and mRNA stability measurements

    PMID:24442868 PMID:38538596

    Open questions at the time
    • Whether these modes operate together is unknown
    • Context-specificity of stabilization not generalized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HSPA1A's distinct activities — cytosolic protein quality control, lysosomal lipid binding, plasma-membrane display, and extracellular receptor engagement — are coordinated and selected within a single cell remains unresolved.
  • No structural model integrating chaperone and lipid-binding functions
  • Trafficking machinery for surface/extracellular HSPA1A unidentified
  • Client-selection rules across compartments undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0001618 virus receptor activity 2 GO:0044183 protein folding chaperone 2 GO:0098772 molecular function regulator activity 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005576 extracellular region 3 GO:0005634 nucleus 3 GO:0005730 nucleolus 2 GO:0005764 lysosome 2 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-9612973 Autophagy 1
Partners
CK2DNAJB1HSPH1LASP1STAM2TLR2TLR4YBX1

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Hsp70.1 (HSPA1A) and Hsp70.3 are required for genomic stability under stress conditions; knockout MEFs show increased chromosome end-to-end associations, radioresistant DNA synthesis, residual chromosome aberrations after ionizing radiation, enhanced cell killing, and increased oncogenic transformation, demonstrating an essential role in DNA damage repair. Gene-targeted knockout mice; MEF irradiation assays; chromosome aberration analysis; oncogenic transformation assays Molecular and cellular biology High 14701760
2001 Hsp70.1 (HSPA1A) is required for maintenance of acquired thermotolerance and protection against heat stress-induced apoptosis; inactivation of hsp70.1 results in deficient thermotolerance at the cellular level, with functional compensation provided by hsp70.3 in single-gene knockouts. Gene-targeted knockout mice (hsp70.1-/- and hsp70.3-/-); thermotolerance assays; apoptosis sensitivity measurements Molecular and cellular biology High 11713291
2001 Hsp70.1 (HSPA1A) plays a cytoprotective role in early brain protection after focal cerebral ischemia; hsp70.1 knockout mice show significantly larger infarction volumes and lower HSP70 protein expression in the ischemic hemisphere compared to wild-type mice. hsp70.1 knockout mice; intraluminal middle cerebral artery occlusion; Northern blot; Western blot; infarction volume measurement Stroke High 11739994
2002 Hsp70.1 (HSPA1A) is specifically required for osmotolerance; osmotic stress selectively induces transcription of hsp70.1 (but not hsp70.3), and hsp70.1-deficient MEFs show markedly reduced cell viability under osmotic stress; hsp70.1-deficient mice exhibit increased apoptosis in the renal medulla under osmotic stress in vivo. hsp70.1-specific knockout mice; osmotic stress treatment; cell viability assays; in vivo renal apoptosis assessment EMBO reports High 12189176
2004 Hsp70.1 (HSPA1A) inhibits the mitochondrial apoptotic pathway after cerebral ischemia; hsp70.1 KO mice show markedly increased cytochrome c release into the cytoplasm and enhanced caspase-3 activation after focal ischemia, resulting in greater DNA fragmentation and infarction volume. hsp70.1 KO mice; focal ischemia model; Western blotting for cytochrome c and caspase-3; TUNEL staining; immunohistochemistry Stroke High 15243143
2003 HSP70.1 (HSPA1A) and HSP70.3 are required for late-phase (but not early-phase) cardioprotection induced by ischemic preconditioning; HSP70.1/3-null mice show no reduction in infarct size after IP at 24 h, whereas wild-type mice show 43% reduction. HSP70.1/3-/- knockout mice; ischemic preconditioning protocol; infarct size measurement after regional ischemia/reperfusion American journal of physiology. Heart and circulatory physiology High 12714332
2005 HSP70.1/3 (HSPA1A) suppresses NF-κB activation and inflammatory cytokine (TNF-α, IL-6) production following sepsis; HSP70.1/3 KO mice show prolonged NF-κB binding/activation in lung tissue, increased TNF-α and IL-6 expression, increased lung injury, and increased mortality after cecal ligation and puncture. HSP70.1/3 KO mice; cecal ligation and puncture sepsis model; NF-κB EMSA; ELISA for cytokines; lung histopathology; survival analysis American journal of physiology. Lung cellular and molecular physiology High 16361353
2010 Activated mu-calpain cleaves Hsp70.1 (HSPA1A) at the lysosomal membrane of post-ischemic hippocampal CA1 neurons, and carbonylation of Hsp70.1 by oxidative stressors (HNE, hydrogen peroxide) markedly increases its susceptibility to calpain cleavage, thereby mediating lysosomal rupture/permeabilization. In vitro cleavage assay of hippocampal Hsp70.1 by mu-calpain; Western blotting; immunofluorescence colocalization of activated mu-calpain and Hsp70.1 at lysosomal membrane; artificial oxidative carbonylation with HNE/H2O2 Biochemical and biophysical research communications High 20171158
2014 Hsp70.1 (HSPA1A) regulates lysosomal stability and neuronal cell fate by binding to the lysosomal lipid bis(monoacylglycero)phosphate (BMP) via its lipid-binding domain, thereby enhancing acid sphingomyelinase (ASM) activity; calpain-mediated cleavage of Hsp70.1 and decreased lysosomal Hsp70.1-BMP levels leads to decreased ASM activity and lysosomal rupture. Hsp70.1-BMP binding analysis; ASM activity measurement; lysosomal fractionation; comparison of motor cortex (neuroprotected) vs. CA1 (neurodegenerated) in post-ischemic monkey; TUNEL assay The Journal of biological chemistry High 25074941
2021 HSPA1A has dual roles in protein quality control: during acute heat stress it promotes recruitment of the 26S proteasome to translating ribosomes, poising cells for rapid protein degradation; during thermotolerance, HSPA1A together with HSPH1 and DNAJB1 maintains ubiquitylated nascent/newly synthesized proteins in a soluble state for efficient proteasomal clearance. Quantitative proteomics; HSPA1A deletion/reconstitution; ribosome-proteasome co-fractionation; ubiquitylated protein solubility assays; mouse tumor growth model with HSPH1 deletion The EMBO journal High 34010456
2015 HspA1A (HSPA1A) interacts with and embeds in anionic phospholipid membranes; the nucleotide-binding domain (NBD) binds lipids more than the substrate-binding domain (SBD), yet the full-length protein is required for membrane embedding; nucleotide binding inhibits lipid binding, while substrate binding does not affect lipid binding. Liposome-binding assays with high potassium; domain-specific binding studies with isolated NBD and SBD; nucleotide competition assays; pH variation studies Cell stress & chaperones High 26342809
2015 HspA1A differentially binds anionic lipids including bis(monoacylglycero)phosphate (BMP), cardiolipin, and sulfatide; the NBD and SBD differentially bind lipids in a lipid-specific manner; nucleotide binding reduces HspA1A-lipid association. Liposome binding assays; domain-specific binding experiments with isolated NBD and SBD; nucleotide competition experiments Biochemical and biophysical research communications Medium 26476215
2019 HspA1A plasma membrane localization depends on its selective interaction with intracellular phosphatidylserine (PS); selective reduction of PS targets by overexpression of the Lact-C2 PS-biosensor greatly reduced HspA1A membrane localization, while reduction of PI(4,5)P2 had minimal effect; PS co-localizes with HspA1A. Confocal microscopy with YFP-tagged HspA1A; cell surface biotinylation; PS-biosensor (Lact-C2) overexpression; PI(4,5)P2-biosensor (PLCδ-PH) overexpression; TopFluor-PS fluorescent lipid analog colocalization Biomolecules High 30999671
2013 Multiple transcription factors coordinately regulate Hspa1a (HSPA1A) promoter: HSF-1 binds at -114/-97 bp and -788/-777 bp, NF-Y at -73/-58 bp, NF-κB at -133/-124 bp, and CREB at -483/-476 bp; siRNA knockdown of each factor reduces endogenous Hspa1a expression; heat-shock induction is coordinately regulated by HSF-1 and NF-Y/NF-κB; TNF-α activates Hspa1a via NF-κB and forskolin via CREB. Promoter-reporter assays; electrophoretic mobility shift assays (EMSA); chromatin immunoprecipitation (ChIP); siRNA knockdown; computational analysis Journal of molecular biology High 24041570
1993 The human HSP70.1 (HSPA1A) gene promoter heat shock element (HSE) was characterized by saturation mutagenesis; positions 1 and 5 of the 5-bp NGAAN motif strongly influence activity in addition to the conserved central triplet; optimal activity occurs with AGAAC; quantitative correlation was found between heat shock factor binding and heat-inducible transcription. Saturation point mutagenesis of HSE; quantitative in vitro heat shock factor binding assays; in vivo transcription assays in HeLa cells The Journal of biological chemistry High 8463341
2013 HSPA1A (HspA1A) facilitates DNA repair in human bronchial epithelial cells after benzo[a]pyrene exposure and directly interacts with casein kinase 2 (CK2); HSPA1A and CK2 co-localize in the nucleus and perinuclear region during DNA repair; HSPA1A overexpression increases CK2 kinase activity. Comet assay; host cell reactivation assay (DRC); mass spectrometry; co-immunoprecipitation; confocal laser scanning microscopy; CK2 kinase activity assay Cell stress & chaperones Medium 23979991
2011 Extracellular HSPA1A promotes hepatocarcinoma cell proliferation and apoptosis-resistance through TLR2 and TLR4 signaling in an NF-κB-dependent manner; HSPA1A also promotes upregulation of TLR4 expression and HMGB1 release from tumor cells. H22 hepatocarcinoma cell treatment with exogenous HSPA1A; TLR2/TLR4 blocking experiments; NF-κB inhibition; proliferation and apoptosis assays Cancer letters Medium 22115967
2012 HSPA1A from ovarian cancer cells interacts with TLR2 and TLR4 on neutrophil surfaces to activate neutrophils and increase reactive oxygen species production. Co-culture of ovarian cancer cells with neutrophils; TLR2/TLR4 blocking experiments; ROS measurement Cell stress & chaperones Medium 22528050
2018 Alcohol-induced HSPA1A selectively suppresses TLR4-MyD88 signaling but not TLR4-TRIF cytokines in monocytes/macrophages; inhibition of PP1 (not HSPA1A) prevents TLR4-TRIF tolerance; HSPA1A is required specifically for TLR4-MyD88 pathway suppression. In vivo binge alcohol exposure in human volunteers; in vitro ethanol treatment of monocytes/macrophages; siRNA knockdown of HSPA1A; cytokine measurement by ELISA and qPCR; IRF3 and TBK1 analysis Journal of immunology Medium 29445009
2014 Nucleolin binds HSPA1A mRNA at its 3' UTR to stabilize it post-transcriptionally, increasing HSPA1A protein expression during myocardial ischemic preconditioning; nucleolin ablation abrogates HSPA1A upregulation induced by preconditioning. RNA-protein interaction studies; reporter gene assays with HSPA1A 3' UTR; nucleolin overexpression and siRNA knockdown in cardiomyocytes; in vivo rat ischemic preconditioning model Cardiovascular research Medium 24442868
2020 HSPA1A protects cells from thermal cytotoxicity by binding to STAM2 (through amino acids 395-509 of HSPA1A), reducing ESCRT-0 and STAM2 levels, which impedes autophagosome-lysosome fusion and abolishes autophagic flux, thereby promoting cell survival during thermoresistance. HSPA1A knockdown/overexpression; co-immunoprecipitation; domain mapping; autophagy flux assays; mouse epidermal thermoresistance model The Journal of investigative dermatology Medium 32533962
2017 HSP70-1 (HSPA1A) is required for IL-5-induced angiogenic responses through eNOS phosphorylation; siRNA knockdown of HSP70-1 suppresses IL-5-induced HUVEC proliferation, migration, tube formation, and eNOS phosphorylation; transcription factor AP-1 drives HSP70-1 expression downstream of ERK and AKT signaling in response to IL-5. siRNA knockdown in HUVECs; HSP70-1 overexpression; HSP70-1 knockout and transgenic mice; angiogenesis animal model; eNOS phosphorylation assays Scientific reports Medium 28317868
2016 HSPA1A overexpression enhances osteogenic differentiation of bone marrow mesenchymal stem cells by upregulating β-catenin and downregulating DKK1 and SOST, activating the Wnt/β-catenin signaling pathway; Wnt/β-catenin inhibitor partially rescues the enhanced osteogenesis. HSPA1A overexpression in BMSCs; osteoblast-specific gene expression; alkaline phosphatase activity; mineral deposition; β-catenin/DKK1/SOST Western blotting; Wnt inhibitor rescue; rat tibial fracture model Scientific reports Medium 27279016
2022 HSPA1A overexpression inhibits apoptosis after spinal cord injury by suppressing Bax, caspase-9, and cleaved-caspase-3, promoting Bcl-2, and activating the Wnt/β-catenin signaling pathway; inhibition of the Wnt/β-catenin pathway attenuates HSPA1A's anti-apoptotic effect. HSPA1A overexpression and silencing in rat SCI model and H2O2-treated cells; apoptosis markers by Western blotting; Wnt/β-catenin pathway inhibitor experiments; neurological function assessment Experimental neurology Medium 36538982
2013 HSPA1A (Hsp70-1) and HSPA6 both localize to stress-sensitive sites including centrioles (proximal end), nuclear speckles, and the granular component of the nucleolus following thermal stress in human neuronal cells; HSPA1A and HSPA8 co-localize with DNAJB1 and HSPH1 at nuclear speckles immediately after heat shock. YFP-tagged HSPA1A stable cell lines in human SH-SY5Y neuronal cells; live confocal microscopy; immunofluorescence with γ-tubulin and centrin markers Cell stress & chaperones Medium 24061851
2016 HSPA1A associates with nuclear speckles and granular component of nucleolus during thermal stress; FRAP analysis shows HSPA1A at centrioles has less prolonged and less dynamic association compared to HSPA6; HSPA6 but not HSPA1A localizes to perispeckles during recovery, suggesting HSPA1A is not involved in transcriptional recovery. YFP-tagged HSPA1A and HSPA6 in human SH-SY5Y cells; live-imaging confocal microscopy; FRAP kinetics measurements Cell stress & chaperones Medium 27527722
2019 LASP1 directly interacts with HSPA1A in head and neck squamous cell carcinoma cells; HSPA1A acts as a chaperone for LASP1, co-localizing in the cytoplasm; HSPA1A positively regulates the interaction of LASP1 with phospho-AKT to enhance malignant cell behavior. Co-immunoprecipitation; confocal colocalization; Western blotting; in vitro and in vivo functional assays Journal of cellular and molecular medicine Medium 31793711
2020 LNCAROD lncRNA acts as a scaffold facilitating the protein-protein interaction between YBX1 and HSPA1A; HSPA1A protects YBX1 from proteasomal degradation when stabilized by LNCAROD; depletion of HSPA1A in LNCAROD-overexpressing cells leads to accelerated proteasomal degradation of YBX1. Co-immunoprecipitation; RNA-protein pulldown; HSPA1A and YBX1 knockdown; protein half-life measurement; proteasome inhibitor experiments Molecular oncology Medium 32216017
2011 NF-κB regulates Hsp70.1 (hspa1a) expression after permanent coronary occlusion, and Hsp70.1 contributes to NF-κB-dependent cardioprotection; Hsp70.1 has antithetical effects on myocardial survival depending on the ischemic stimulus (protective after permanent occlusion, injurious after ischemia/reperfusion). Microarray analysis; mice with genetic abrogation of NF-κB in the heart; Hsp70.1 knockout mice; infarct size measurement after permanent coronary occlusion Journal of molecular and cellular cardiology Medium 21439970
2008 Hsp70.1 (HSPA1A) is critically required for T cell activation against myelin antigens; hsp70.1-/- mice are highly resistant to experimental autoimmune encephalomyelitis (EAE), with loss of T cell proliferation and IFN-γ production to MOG peptide; T cell transfer and antigen presentation assays demonstrate the defect is in activation of autoreactive T cells, with CD4+ T cells more prone to TCR-induced apoptosis. hsp70.1-/- mice; EAE sensitization; T cell proliferation assays; IFN-γ ELISA; T cell transfer experiments; in vitro antigen presentation assays European journal of immunology High 18581325
2015 Hsp70.1 (HSPA1A) prevents human islet amyloid polypeptide (h-IAPP) aggregation and toxicity; Hsp70.1 overexpression in pancreatic β-cells ameliorates h-IAPP toxicity; co-expression of h-Hsp72 with h-proIAPP in C. elegans increases h-proIAPP solubility. Hsp70.1 overexpression in pancreatic β-cells; C. elegans transgenic model expressing h-proIAPP ± h-Hsp72; protein aggregation/solubility assays; cell viability assays PloS one Medium 26960140
2015 CVB3 infection upregulates Hsp70-1 (HSPA1A) via CaMKIIγ-dependent phosphorylation of HSF1 at Serine 230, which enhances Hsp70-1 transcription and induces HSF1 nuclear translocation, blocking ERK1/2-mediated phosphorylation of HSF1 at Ser307 (a negative regulatory site); upregulated Hsp70-1 in turn stabilizes CVB3 genome RNA via the AU-rich element (ARE) in the 3' UTR. In vitro and in vivo CVB3 infection; HSF1 phosphorylation-site mutants; CaMKIIγ inhibition; ARE functional assays; mRNA stability measurements Cellular and molecular life sciences Medium 26361762
2000 Transcription of hsp70.1 (HSPA1A) at zygotic genome activation requires the contiguity of a GC box with a GAGA box and involves Sp1 and a novel GAGA box-binding factor structurally related to Drosophila GAGA factor; the novel GAGA factor acts as a transcriptional coactivator/potentiator of Sp1 and is of maternal origin, present in unfertilized eggs through the two-cell stage. In vivo transcription factor titration with double-stranded oligodeoxyribonucleotides; antibody microinjection into embryos; transgenic mice with hsp70.1 promoter-reporter constructs Development Medium 10704399
1997 HSE boxes in the HSP70.1 (HSPA1A) promoter are required for spontaneous transcriptional activation during zygotic genome activation; mHSF1 is present in the nucleus from the one-cell stage and participates in this atypical stress-independent activation through HSE sequences. HSE mutagenesis in transgenic embryos; competition experiments with oligonucleotides; immunolocalization of mHSF1 Molecular and cellular biology Medium 9001232
2023 Hydroxynonenal (HNE)-mediated carbonylation of Hsp70.1 (HSPA1A) facilitates calpain-mediated cleavage of Hsp70.1, leading to lysosomal membrane permeabilization/rupture and cathepsin leakage, causing cell degeneration/death in neurons, pancreatic cells, and hepatocytes; this pathway is implicated in Alzheimer's disease, type 2 diabetes, and NASH. Review summarizing previously published in vitro cleavage assays and in vivo animal/primate models; HNE carbonylation experiments; lysosomal stability assays Frontiers in molecular biosciences Medium 36819480
2024 METTL3-mediated m6A modification increases stability of Hspa1a mRNA in osteoblasts; YTHDF2 acts to stabilize (rather than degrade) Hspa1a mRNA in this context, and METTL3-enhanced Hspa1a expression inhibits osteoblast aging. MeRIP-seq; METTL3 overexpression; YTHDF2 knockdown; mRNA stability assays; osteoblast aging phenotype readouts Cell death discovery Medium 38538596
2001 Hsp70-1 (HSPA1A) and Hsp70-3 are both necessary and sufficient to prevent arsenite-induced neural tube defects in mouse embryos; antisense knockdown of hsp70-1/3 increased arsenite-induced neural tube defects up to six-fold, while constitutive overexpression of hsp70-1 transgene decreased defect incidence. Antisense oligonucleotide injection into cultured mouse embryos; constitutive hsp70-1 transgene microinjection; arsenite-induced dysmorphology assay Molecular reproduction and development Medium 11424214
2099 Exogenous HSPA1A induces dose-dependent IL-1β, TNF-α, and IL-10 secretion from differentiated U937 cells and PBMCs; HSPA1A interacts with extracellular receptor proteins CD14, CD36, and CD11b; CD14 affects the levels of cytokine secretion in response to exogenous HSPA1A; cytokine induction is largely independent of contaminating LPS. ELISA for cytokines; exogenous HSPA1A treatment of U937 cells and PBMCs; CD14/CD36/CD11b interaction assays; LPS-depletion controls FEBS open bio Medium 37583307

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2009 Circulating heat shock protein 70 (HSPA1A) in normal and pathological pregnancies. Cell stress & chaperones 77 19821156
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
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
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 60 16361353
2004 Effects of hsp70.1 gene knockout on the mitochondrial apoptotic pathway after focal cerebral ischemia. Stroke 60 15243143
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
2000 A developmentally regulated GAGA box-binding factor and Sp1 are required for transcription of the hsp70.1 gene at the onset of mouse zygotic genome activation. Development (Cambridge, England) 56 10704399
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
1997 Evidence for the involvement of mouse heat shock factor 1 in the atypical expression of the HSP70.1 heat shock gene during mouse zygotic genome activation. Molecular and cellular biology 52 9001232
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
2016 Plasmodium falciparum Hsp70-z, an Hsp110 homologue, exhibits independent chaperone activity and interacts with Hsp70-1 in a nucleotide-dependent fashion. Cell stress & chaperones 44 26894764
2010 Extracellular heat shock protein 70 (HSPA1A) and classical vascular risk factors in a general population. Cell stress & chaperones 44 20490736
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 43 24041570
2012 Plasma Hsp72 (HSPA1A) and Hsp27 (HSPB1) expression under heat stress: influence of exercise intensity. Cell stress & chaperones 43 22222935
2009 Functional SNPs in HSPA1A gene predict risk of coronary heart disease. PloS one 43 19333379
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
2024 METTL3-mediated m6A modification increases Hspa1a stability to inhibit osteoblast aging. Cell death discovery 34 38538596
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
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 31 19241595
2019 Membrane Localization of HspA1A, a Stress Inducible 70-kDa Heat-Shock Protein, Depends on Its Interaction with Intracellular Phosphatidylserine. Biomolecules 30 30999671
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
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 28 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
2018 Structure-based drug designing and identification of Woodfordia fruticosa inhibitors targeted against heat shock protein (HSP70-1) as suppressor for Imiquimod-induced psoriasis like skin inflammation in mice model. Materials science & engineering. C, Materials for biological applications 25 30573271
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 25 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
2006 Genes and longevity: a genetic-demographic approach reveals sex- and age-specific gene effects not shown by the case-control approach (APOE and HSP70.1 loci). Biogerontology 22 16896546
2021 Targeting HSPA1A in ARID2-deficient lung adenocarcinoma. National science review 21 34858604
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 21 31793711
2014 Nucleolin involved in myocardial ischaemic preconditioning via post-transcriptional control of HSPA1A expression. Cardiovascular research 21 24442868
2020 Comparative Characterization of Plasmodium falciparum Hsp70-1 Relative to E. coli DnaK Reveals the Functional Specificity of the Parasite Chaperone. Biomolecules 20 32512819
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 Downhill running and exercise in hot environments increase leukocyte Hsp72 (HSPA1A) and Hsp90α (HSPC1) gene transcripts. Journal of applied physiology (Bethesda, Md. : 1985) 18 25722377
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 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
2023 Exogenous heat shock proteins HSPA1A and HSPB1 regulate TNF-α, IL-1β and IL-10 secretion from monocytic cells. FEBS open bio 16 37583307
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
2012 Expression and characterization of constitutive heat shock protein 70.1 (HSPA-1A) gene in in vitro produced and in vivo-derived buffalo (Bubalus bubalis) embryos. Reproduction in domestic animals = Zuchthygiene 15 22463675
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
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 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 13 28182740
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

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