Affinage

HSPA6

Heat shock 70 kDa protein 6 · UniProt P17066

Length
643 aa
Mass
71.0 kDa
Annotated
2026-06-10
68 papers in source corpus 34 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSPA6 (HSP70B') is a strictly stress-inducible 70 kDa HSP70-family chaperone that binds ATP and provides cytoprotection against proteotoxic insults (PMID:2327978, PMID:17915554, PMID:18229458). It has little or no basal expression and is transcribed only upon strong stress, downstream of heat shock elements engaging HSF-family factors together with an AP1 element (PMID:1346391, PMID:25073946), and is additionally induced by HSP90 inhibition, proteasome inhibition, eNOS-derived nitric oxide, oncogenic Ha-Ras, TRPA1 activation, and a range of transcriptional and epigenetic inputs (BARX1, ATF3, CITED2-EP300, TRIM35-driven H3K27ac, and histone lactylation) (PMID:16278678, PMID:25957766, PMID:26656590, PMID:30200301, PMID:41136372, PMID:41616844, PMID:36927457, PMID:41456178). As a chaperone it cooperates with the HSP70 machinery, forming heteromeric complexes with Hsp72, Hsc70, HOP, and Hsp40, where knockdown of either HSPA6 or Hsp72 abolishes acquired cytoprotection (PMID:18579131, PMID:20084477). After thermal stress HSPA6 redistributes sequentially to centrioles, nuclear speckles, the nucleolar granular component, and the periphery of nuclear speckles (perispeckles), a transcription-site localization that is unique to HSPA6 and dependent on active RNA polymerase II, implicating it in transcriptional recovery (PMID:24061851, PMID:25319762, PMID:27743288). Beyond canonical chaperone roles, HSPA6 acts as a negative regulator of antiviral type-I interferon signaling by binding RIG-I and MDA5 to disrupt their multimerization and by blocking the TRAF3-IKKε interaction to suppress IFN-β (PMID:38088561, PMID:41762233). It also engages disease-relevant effector pathways: it binds and stabilizes anti-apoptotic Bcl-XL (PMID:26826017), binds NF-κB p65 to suppress lipogenesis and promote ferroptosis through a palmitoylation-dependent feedback loop with ANKIB1 (PMID:42088412), and recruits ROCK2 to phosphorylate and activate IMPDH2 (S416), driving GTP synthesis and radioresistance (PMID:42234559).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1990 Medium

    Established HSPA6 as a distinct, highly stress-inducible HSP70 paralog with ATP-binding capacity, setting the expectation of chaperone function.

    Evidence cDNA isolation, hybrid-selected translation, Northern blot, and ATP-binding assay

    PMID:2327978

    Open questions at the time
    • No direct reconstitution of chaperone/refolding activity
    • No mutagenesis of the nucleotide-binding domain
  2. 1992 Medium

    Mapped HSPA6 to chromosome 1q and confirmed its expression is restricted to heat stress with no detectable basal mRNA, defining its tight stress-gating.

    Evidence Somatic cell hybrid panel hybridization and Northern blot

    PMID:1346391

    Open questions at the time
    • No information on tissue-specific induction thresholds
  3. 2014 Medium

    Dissected how the HSPA6 promoter is held silent at 37°C and activated under stress, identifying HSE and AP1 elements and HSF1 regulation by repressors (NFIL6, Ku70) and inducers (Ha-Ras).

    Evidence Promoter reporter/truncation/mutagenesis assays, EMSA, HSF1-null and Ku-deficient cells

    PMID:11162511 PMID:16278678 PMID:25073946

    Open questions at the time
    • Identity of the non-HSF1 stress-inducible HSE-binding factor in keratinocytes unresolved
    • Extracellular regulator of cell-number-dependent induction not identified
  4. 2008 Medium

    Demonstrated that HSPA6 is functionally cytoprotective and acts cooperatively within the HSP70 chaperone network rather than in isolation.

    Evidence siRNA knockdown with viability assays plus Co-IP with Hsp72, Hsc70, HOP, and Hsp40

    PMID:17915554 PMID:18229458 PMID:18579131 PMID:20084477

    Open questions at the time
    • Substrate repertoire and co-chaperone selectivity not defined
    • Co-IPs from single labs without reciprocal validation for some partners
  5. 2016 Medium

    Defined a unique HSPA6 stress-relocalization itinerary culminating at transcription sites, linking the chaperone to transcriptional recovery after stress.

    Evidence Live-cell confocal microscopy, FRAP, marker co-localization, and triptolide perturbation in SH-SY5Y cells

    PMID:24061851 PMID:25319762 PMID:27527722 PMID:27743288 PMID:28484369

    Open questions at the time
    • Molecular cargo or function at perispeckles not identified
    • Mechanism distinguishing HSPA6 from HSPA1A targeting unknown
  6. 2023 High

    Revealed a non-chaperone role: HSPA6 suppresses antiviral type-I interferon signaling, identifying a host factor exploited by pathogens.

    Evidence CUT&Tag+RNA-seq, Co-IP of TRAF3-IKKε, siRNA/overexpression, and IFN-β reporter assays

    PMID:38088561

    Open questions at the time
    • Structural basis of TRAF3-IKKε disruption not resolved
    • Whether chaperone activity is required for this function unknown
  7. 2025 Medium

    Extended HSPA6's immune-suppressive role upstream to the receptor level, showing it binds RIG-I and MDA5 to block their multimerization.

    Evidence Co-IP of HSPA6 with RIG-I/MDA5, RLR multimer assay, and genetic epistasis (MAVS-/-, IRF3-/-, IRF1, AP-1)

    PMID:41762233

    Open questions at the time
    • Binding interface on RIG-I/MDA5 not mapped
    • Relationship to the TRAF3-IKKε mechanism not integrated
  8. 2026 Medium

    Connected HSPA6 to effector pathways in cancer—apoptosis, lipid metabolism/ferroptosis, and purine biosynthesis—showing direct binding partners that it stabilizes, sequesters, or activates.

    Evidence Co-IP (Bcl-XL, NF-κB p65, IMPDH2, ROCK2), phospho-site mapping (IMPDH2 S416), lipid/ferroptosis and ubiquitination assays, in vivo GBM model

    PMID:26826017 PMID:42088412 PMID:42234559

    Open questions at the time
    • Whether these interactions reflect chaperone holding versus dedicated scaffolding is unclear
    • Most mechanisms from single labs without independent replication
  9. 2026 Medium

    Identified additional transcriptional/epigenetic inducers (BARX1, ATF3, CITED2-EP300, TRIM35-H3K27ac, histone lactylation) coupling HSPA6 induction to proliferation, metastasis, ferroptosis, and cuproptosis outcomes.

    Evidence ChIP, reporter assays, histone modification assays, siRNA/rescue, and in vivo tumor/IRI models

    PMID:36927457 PMID:40313859 PMID:40765077 PMID:41136372 PMID:41456178 PMID:41616844

    Open questions at the time
    • Context-specificity of pro- versus anti-tumor effects unresolved
    • Direct downstream chaperone substrates in these settings unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown what physiological client proteins HSPA6 holds or refolds and how its substrate-binding domain selectivity relates to its diverse non-canonical scaffolding/regulatory functions.
  • No defined client/substrate spectrum
  • No structural model of HSPA6-specific interactions
  • Mechanism reconciling chaperone versus signaling roles unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0044183 protein folding chaperone 3 GO:0140657 ATP-dependent activity 1
Localization
GO:0005654 nucleoplasm 2 GO:0005730 nucleolus 2 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
BCL2L1HSPA1AHSPA8HSPC70IFIH1IMPDH2RIGISTIP1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 HSPA6 (HSP70B') encodes a novel stress-inducible 70 kDa protein that binds ATP, consistent with chaperone function. It has little or no basal expression and is induced only at higher temperatures compared to the major inducible HSP70. cDNA isolation, hybrid-selected translation, Northern blot, S1 nuclease protection, ATP-binding assay The Biochemical journal Medium 2327978
1992 HSPA6 maps to human chromosome 1q and is expressed as an mRNA only upon heat stress, with no basal expression detectable. Somatic cell hybrid panel hybridization, Northern blot with specific oligonucleotides Genomics Medium 1346391
2001 The HSP70B (HSPA6) promoter is repressed at 37°C by three independent mechanisms: (1) NFIL6 displaces HSF1 from the heat shock element (HSE) independently of Ku70; (2) Ku70 binds HSF1 and displaces it from the HSE in vitro; (3) MAPK/GSK3-mediated phosphorylation of HSF1 at Ser303/Ser307 contributes independently. In Ku-deficient cells, HSF1 activation of the HSP70B promoter is greatly enhanced. Promoter reporter assays, HSF1 mutant analysis, in vitro translated Ku70 binding/displacement assay, Ku-deficient cell lines Biochemical and biophysical research communications Medium 11162511
2006 Ha-Ras(val12) induces HSPA6 (HSP70b) transcription via heat shock elements (HSEs) in an HSF1-dependent manner. Stable Ha-ras(val12)-transformed cells, however, suppress HSPA6 expression, correlating with increased sensitivity to heat shock. Transient transfection of HSP70b promoter-reporter constructs, systematic deletions and point mutations, HSF1-/- cells Oncogene Medium 16278678
2007 siRNA knockdown of HSPA6 (Hsp70B') sensitizes human colon cells to heat stress and proteasome inhibition, establishing a direct cytoprotective function. HSPA6 is a secondary stress responder relative to Hsp72, but ZnSO4 induces HSPA6 specifically (not Hsp72), indicating stressor-specific primary roles. siRNA knockdown, flow cytometry viability assay, promoter-GFP flow cytometry Cell stress & chaperones Medium 17915554 18229458
2007 HSPA6 (Hsp70B') expression is cell-number-dependent, being optimally induced at low cell numbers. Medium conditioned from low-cell-number cultures promotes Hsp70B' promoter activation in high-cell-number cultures, indicating an extracellular regulator. This regulation is not explained by changes in HSF-1 DNA-binding activity or hyperphosphorylation. Flow cytometry using Hsp70B' promoter-driven GFP construct, conditioned medium transfer experiments, HSF-1 EMSA Journal of cellular physiology Medium 17044073
2008 HSPA6 (Hsp70B') forms a complex with Hsp72 and the co-chaperone HOP following heat stress in human colon cells. siRNA knockdown of either Hsp70B' or Hsp72 severely impairs acquisition of cytoprotection, supporting cooperative roles in cell survival. Co-immunoprecipitation, siRNA knockdown, flow cytometry viability assay Experimental cell research Medium 18579131
2008 HSPA6 (Hsp70B') is expressed on the cell surface in response to proteasome inhibition (but not heat shock) in certain human colon cell lines. Phylogenetic analysis indicates that Hsp70B' and Hsp72 share 100% identity in their predicted peptide-binding regions, suggesting they bind the same substrates, while sequence differences in lid and C-terminal domains suggest different co-chaperone or receptor interactions. Flow cytometry for surface expression, phylogenetic sequence analysis Cell stress & chaperones Low 18347947
2010 HSPA6 (Hsp70B') forms heteromeric complexes with Hsp70, Hsc70, and Hsp40 in differentiated human neuronal cells, detected by co-immunoprecipitation. Co-immunoprecipitation from differentiated SH-SY5Y human neuronal cells Cell stress & chaperones Low 20084477
2010 In macrophages, oxLDL immune complexes (oxLDL-IC) induce synthesis and release of HSPA6 (HSP70B'). Released HSP70B' co-localizes with cell-associated and internalized lipid moiety of oxLDL-IC. siRNA knockdown of HSP70B' decreased sphingosine kinase 1 (SK1) mRNA levels and SK1 phosphorylation, and increased IL-10 release, implicating HSPA6 in regulating SK1 activity and IL-10 secretion. Immunoblot, confocal fluorescence microscopy, HSP70B'-GFP transfection, siRNA knockdown, SK1 phosphorylation assay The Journal of biological chemistry Medium 20348092
2013 Following thermal stress, YFP-tagged HSPA6 (and HSPA1A) rapidly localizes to the proximal end of centrioles in differentiated human SH-SY5Y neuronal cells, with HSPA6 showing a more prolonged signal than HSPA1A. Live-cell fluorescence microscopy of YFP-tagged HSPA6 in stable cell lines, co-staining with γ-tubulin and centrin markers Cell stress & chaperones Medium 24061851
2014 Following heat shock in differentiated human SH-SY5Y neuronal cells, YFP-HSPA6 localizes sequentially to nuclear speckles (SC35/SON-positive RNA splicing factor compartments), then the granular component of the nucleolus (nucleophosmin-positive), and subsequently to the periphery of nuclear speckles (perispeckles) that are sites of RNA transcription. This perispeckle localization is unique to HSPA6 and not observed for HSPA1A. Stable YFP-tagged HSPA6 expression in SH-SY5Y cells, confocal microscopy, co-localization with SC35, SON, and nucleophosmin markers Journal of neurochemistry Medium 25319762
2014 The HSPA6 promoter contains negative and positive regulatory regions across 3 kb. A region between -346 and -217 bp is critical for basal expression and stress inducibility. An AP1 site within this region contributes to basal expression and maximal stress induction. A newly characterized HSE in this region mediates heat-induced transcription but preferentially binds a stress-inducible factor other than HSF1 or HSF2 in HaCaT keratinocytes, yet binds both HSF1 and HSF2 from other epithelial cell extracts. Promoter 5' truncations and deletions, site-specific mutagenesis, DNA-binding (EMSA) studies, luciferase reporter assays Cell stress & chaperones Medium 25073946
2015 HSPA6 is strongly and specifically induced by HSP90 inhibitors (17-AAG and Radicicol) in certain cancer cell lines. siRNA-mediated inhibition or recombinant overexpression of HSPA6 did not influence 17-AAG-mediated cell death, indicating HSPA6 is not required for this cytotoxic effect. qPCR, Western blot, siRNA knockdown, recombinant overexpression, cell viability assay FEBS letters Medium 25957766
2015 eNOS-derived nitric oxide induces HSPA6 expression (~14-fold) in human coronary artery smooth muscle cells. Adenoviral overexpression of HSPA6 inhibits smooth muscle cell proliferation, paralleling the eNOS anti-proliferative effect. Adenoviral transduction (Ad-eNOS), whole-genome array, qPCR, immunoblotting, adenoviral HSPA6 overexpression, proliferation assay Nitric oxide : biology and chemistry Medium 26656590
2016 HSPA6 targeting to the periphery of nuclear speckles (perispeckles, transcription sites) after thermal stress is disrupted by the transcription inhibitor triptolide, which knocks down RNA polymerase II large subunit RPB1. This links HSPA6 perispeckle localization to active transcription and suggests a role in transcriptional recovery after neuronal stress. Confocal microscopy of YFP-HSPA6 in SH-SY5Y cells treated with triptolide, Western blot for RPB1 Neurochemical research Medium 27743288
2016 HSPA6 shows a more prolonged and dynamic association with stress-sensitive structures (centrioles, nuclear speckles, nucleolus, perispeckles) compared to HSPA1A, as measured by FRAP. The stress-induced association of HSPA6 with perispeckles (transcription sites) displays the greatest dynamism among all structures examined. Live-cell confocal microscopy and FRAP of YFP-tagged HSPA6 and HSPA1A in differentiated SH-SY5Y cells Cell stress & chaperones Medium 27527722
2016 HSPA6 co-immunoprecipitates with anti-apoptotic Bcl-XL in intestinal epithelial cells. Cigarette smoke extract (CSE) strongly induces HSPA6, which stabilizes Bcl-XL protein levels (without altering Bcl-XL mRNA), thereby protecting intestinal epithelial cells from apoptosis. Immunoprecipitation, Q-PCR, Western blotting, immunofluorescence microscopy Biochimica et biophysica acta Medium 26826017
2017 siRNA knockdown of HSPA6 and HSPA1A in differentiated human SH-SY5Y neuronal cells abolishes the protective effect of co-applied celastrol/arimoclomol against heat shock, establishing that both HSPs contribute to protection of human neuronal cells from thermal stress. siRNA knockdown, cell viability assay after heat shock, celastrol/arimoclomol co-treatment Neurochemical research Medium 29090408
2017 After heat shock in differentiated human neuronal cells, HSPA6 targets the periphery of nuclear speckles (perispeckles/transcription sites) but does NOT co-localize with DNAJB1 (Hsp40-1) or HSPH1 (Hsp105α) at this site. At 3 h post-heat shock, HSPA6 co-localizes with DNAJB1 and HSPH1 at the granular component of the nucleolus. By contrast, HSPA1A and HSPA8 co-localize with these disaggregation machine components at nuclear speckles immediately after heat shock. Confocal microscopy of YFP-tagged HSPA6 with co-staining for DNAJB1, HSPH1, DNAJA1, and BAG-1 in differentiated SH-SY5Y cells Frontiers in neuroscience Medium 28484369
2018 Sulfur mustard (SM)-induced HSPA6 protein upregulation is mediated through TRPA1 ion channel activation. Pre-treatment with the specific TRPA1 inhibitor AP18 diminishes SM-induced HSPA6 upregulation, establishing TRPA1 as an upstream regulator. 2D gel electrophoresis proteomics, MALDI-TOF mass spectrometry, RT-qPCR, TRPA1 inhibitor (AP18) treatment in TRPA1-overexpressing HEK cells and endogenous A549 cells Cells Medium 30200301
2023 HSPA6 impedes IFN-β production by blocking the interaction between TRAF3 and IKKε, thereby suppressing antiviral innate immune signaling. This function is exploited by PRRSV through virus-induced lactylation, which transcriptionally activates HSPA6. CUT&Tag combined with RNA-seq, co-immunoprecipitation (TRAF3-IKKε interaction), siRNA knockdown, overexpression, IFN-β reporter assay Journal of virology High 38088561
2025 HSPA6 binds to NF-κB p65 and inhibits its nuclear translocation and Ser468 phosphorylation, suppressing transcription of lipogenic enzyme FASN and downregulating LPCAT1/cPLA2, which enriches membrane phospholipids with polyunsaturated fatty acids and promotes ferroptosis in triple-negative breast cancer cells. Concurrently, HSPA6-mediated suppression of lipogenesis depletes palmitate, impairing ANKIB1 palmitoylation and inhibiting ANKIB1 E3 ligase-mediated K48-linked ubiquitination of HSPA6, forming a stabilizing feedback loop. Co-IP (HSPA6-p65 binding), nuclear fractionation, Western blot for p65 phosphorylation, FASN/LPCAT1/cPLA2 expression, lipid peroxidation assays, ANKIB1 palmitoylation assay, ubiquitination assay International journal of biological sciences Medium 42088412
2025 HSPA6 is induced by RIG-I-like receptor (RLR) activation and acts as a negative regulator of type-I interferon signaling. HSPA6 induction is independent of MAVS or IRF3 but depends on E3 ligases associated with RLRs, stress granules, and transcription factors IRF1 and AP-1. HSPA6 binds to RIG-I and MDA5 in the cytoplasm and disrupts their multimer complex formation. Co-immunoprecipitation (HSPA6-RIG-I/MDA5 binding), Western blot, RLR multimer assay, genetic epistasis (MAVS-/-, IRF3-/-, IRF1 knockdown, AP-1 inhibition), IFN-β reporter assay Cellular and molecular life sciences : CMLS Medium 41762233
2025 TRIM35 directly binds the HSPA6 promoter, catalyzes non-proteolytic ubiquitination of histone H3, which recruits p300 to mediate H3K27 acetylation, thereby activating HSPA6 transcription. This epigenetic mechanism underlies TRIM35's tumor-suppressive effect in breast cancer that is mediated through HSPA6 upregulation. ChIP (TRIM35 promoter binding), co-immunoprecipitation (TRIM35-H3 interaction), H3 ubiquitination assay, H3K27 acetylation assay, p300 recruitment assay, siRNA knockdown, reporter assays Cell death discovery Medium 41136372
2026 HSPA6 interacts with IMPDH2, a rate-limiting enzyme in purine biosynthesis, and promotes GTP synthesis to drive radioresistance in glioblastoma stem cells. Mechanistically, HSPA6 recruits ROCK2 kinase to phosphorylate IMPDH2 at S416, activating it. Combined pharmacological inhibition of HSPA6 and IMPDH2 with irradiation significantly improves survival in GBM mouse models. Co-immunoprecipitation (HSPA6-IMPDH2, HSPA6-ROCK2), IMPDH2 phosphorylation assay (S416), GTP synthesis assay, siRNA knockdown, in vivo mouse GBM model, pharmacological inhibition Cell reports Medium 42234559
2026 Lactate-induced H3K18 lactylation at the HSPA6 locus transcriptionally activates HSPA6 expression during renal ischemia-reperfusion injury. Elevated HSPA6 then promotes cuproptosis and worsens renal damage. Knockdown of HSPA6 suppresses OGD/R-induced cuproptosis. Multi-omics (proteomics, CUT&Tag, RNA-seq), ChIP-qPCR (H3K18la at HSPA6 locus), LDHA inhibition, HSPA6 knockdown, in vivo IRI mouse model Life sciences Medium 41616844
2025 BARX1 transcription factor directly activates HSPA6 transcription, as confirmed by dual-luciferase reporter assay with BARX1 binding to the HSPA6 promoter. HSPA6 knockdown attenuates BARX1-induced osteosarcoma cell proliferation and migration. RNA sequencing after BARX1 overexpression, dual-luciferase reporter assay, siRNA knockdown, proliferation and migration assays, dual immunofluorescence Journal of orthopaedic surgery and research Medium 36927457
2025 CAIX overexpression activates HSPA6 expression through the AMPK signaling pathway in osteosarcoma cells, promoting cell migration and invasion. Pharmacological AMPK inhibition (dorsomorphin) suppresses CAIX-induced HSPA6 expression and metastasis. HSPA6 knockdown reduces CAIX-driven migration and invasion. CAIX overexpression, siRNA knockdown of HSPA6, Western blot for AMPK phosphorylation, AMPK inhibitor (dorsomorphin), migration/invasion assays Journal of cellular and molecular medicine Medium 40765077
2025 ZT-22, a benzofuran derivative of β-elemene, directly binds HSPA6 protein. This binding activates the p38 MAPK signaling pathway and inhibits HCC cell growth. HSPA6 knockdown diminishes p38 MAPK signaling and reverses ZT-22 anti-HCC effects. DARTS combined with mass spectrometry for target identification; CETSA, SPR, microscale thermophoresis (MST), molecular docking, molecular dynamics simulations for binding validation; siRNA knockdown with p38 MAPK readout Chemico-biological interactions High 40239884
2025 HSPB6 directly interacts with HSPA6 (detected by immunoprecipitation mass spectrometry), and HSPB6 overexpression inhibits the JNK-JUND signaling axis downstream of HSPA6, suppressing colorectal cancer progression. Immunoprecipitation mass spectrometry, Western blot, RNA sequencing, in vivo tumor model Life sciences Low 41043501
2025 CITED2 binds EP300 and regulates HSPA6 gene expression; CITED2 knockdown in human spermatogonial stem cell lines significantly inhibits proliferation and increases apoptosis, and overexpression of HSPA6 rescues these effects, placing HSPA6 downstream of the CITED2-EP300 complex via the MAPK pathway. siRNA knockdown, RNA sequencing, immunoprecipitation (CITED2-EP300), HSPA6 overexpression rescue assay Stem cells international Medium 40313859
2025 ATF3 binds the HSPA6 promoter to activate its transcription downstream of PERP upregulation. PERP overexpression suppresses breast cancer metastasis, and knockdown of ATF3 or HSPA6 eliminates this antimetastatic effect, establishing a PERP-ATF3-HSPA6 axis. Chromatin immunoprecipitation (ATF3 at HSPA6 promoter), siRNA knockdown, RNA-seq, Western blot, RT-qPCR, migration/invasion assays, in vivo metastasis model The Journal of international medical research Medium 41456178

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 The human heat-shock protein family. Expression of a novel heat-inducible HSP70 (HSP70B') and isolation of its cDNA and genomic DNA. The Biochemical journal 161 2327978
2015 Upregulation of heat shock proteins (HSPA12A, HSP90B1, HSPA4, HSPA5 and HSPA6) in tumour tissues is associated with poor outcomes from HBV-related early-stage hepatocellular carcinoma. International journal of medical sciences 149 25798051
2005 J-domain protein CDJ2 and HSP70B are a plastidic chaperone pair that interacts with vesicle-inducing protein in plastids 1. Molecular biology of the cell 109 15635096
2007 Hsp70B' regulation and function. Cell stress & chaperones 68 18229458
2005 HEAT SHOCK PROTEIN 90C is a bona fide Hsp90 that interacts with plastidic HSP70B in Chlamydomonas reinhardtii. Plant physiology 59 15995001
1992 The human heat-shock genes HSPA6 and HSPA7 are both expressed and localize to chromosome 1. Genomics 56 1346391
2000 The human Hsp70B gene at the HSPA7 locus of chromosome 1 is transcribed but non-functional. Biochimica et biophysica acta 48 11072087
2017 HSPA6 augments garlic extract-induced inhibition of proliferation, migration, and invasion of bladder cancer EJ cells; Implication for cell cycle dysregulation, signaling pathway alteration, and transcription factor-associated MMP-9 regulation. PloS one 46 28187175
2005 Ectoine from halophilic microorganisms induces the expression of hsp70 and hsp70B' in human keratinocytes modulating the proinflammatory response. Cell stress & chaperones 44 16184764
2021 RNA-Sequencing Reveals Heat Shock 70-kDa Protein 6 (HSPA6) as a Novel Thymoquinone-Upregulated Gene That Inhibits Growth, Migration, and Invasion of Triple-Negative Breast Cancer Cells. Frontiers in oncology 38 34017687
2014 Basal and stress-inducible expression of HSPA6 in human keratinocytes is regulated by negative and positive promoter regions. Cell stress & chaperones 37 25073946
2008 Hsp70B' and Hsp72 form a complex in stressed human colon cells and each contributes to cytoprotection. Experimental cell research 36 18579131
2022 HSPA6 and its role in cancers and other diseases. Molecular biology reports 34 35666422
2007 Hsp70B' regulation and function. Cell stress & chaperones 34 17915554
2023 Lactate-lactylation-HSPA6 axis promotes PRRSV replication by impairing IFN-β production. Journal of virology 33 38088561
2007 Cell number-dependent regulation of Hsp70B' expression: evidence of an extracellular regulator. Journal of cellular physiology 32 17044073
2017 Knockdown of Heat Shock Proteins HSPA6 (Hsp70B') and HSPA1A (Hsp70-1) Sensitizes Differentiated Human Neuronal Cells to Cellular Stress. Neurochemical research 29 29090408
2008 Surface expression of Hsp70B' in response to proteasome inhibition in human colon cells. Cell stress & chaperones 28 18347947
2014 Localization of heat shock protein HSPA6 (HSP70B') to sites of transcription in cultured differentiated human neuronal cells following thermal stress. Journal of neurochemistry 27 25319762
2008 Insulated hsp70B' promoter: stringent heat-inducible activity in replication-deficient, but not replication-competent adenoviruses. The journal of gene medicine 27 18265421
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
2020 Regulatory roles of HSPA6 in Actinidia chinensis Planch. root extract (acRoots)-inhibited lung cancer proliferation. Clinical and translational medicine 23 32508044
2013 Stress-induced localization of HSPA6 (HSP70B') and HSPA1A (HSP70-1) proteins to centrioles in human neuronal cells. Cell stress & chaperones 23 24061851
2005 Rapid and highly sensitive detection of cadmium chloride induced cytotoxicity using the HSP70B' promoter in live cells. Biotechnology and bioengineering 23 16155950
2010 Heteromeric complexes of heat shock protein 70 (HSP70) family members, including Hsp70B', in differentiated human neuronal cells. Cell stress & chaperones 22 20084477
2010 Heat shock protein 70B' (HSP70B') expression and release in response to human oxidized low density lipoprotein immune complexes in macrophages. The Journal of biological chemistry 22 20348092
2007 Highly sensitive detection of cytotoxicity using a modified HSP70B' promoter. Biotechnology and bioengineering 22 17163517
2015 Optimization of expression and purification of HSPA6 protein from Camelus dromedarius in E. coli. Saudi journal of biological sciences 21 27081368
2008 Assistance for a chaperone: Chlamydomonas HEP2 activates plastidic HSP70B for cochaperone binding. The Journal of biological chemistry 21 18420590
2015 Induction of heat shock protein HSPA6 (HSP70B') upon HSP90 inhibition in cancer cell lines. FEBS letters 20 25957766
2006 Ha-ras(val12) induces HSP70b transcription via the HSE/HSF1 system, but HSP70b expression is suppressed in Ha-ras(val12)-transformed cells. Oncogene 20 16278678
1998 Effect of low-dose preirradiation on induction of the HSP70B-LacZ fusion gene in human cells treated with heat shock. Radiation research 18 9457900
2022 HSPA6 is Correlated With the Malignant Progression and Immune Microenvironment of Gliomas. Frontiers in cell and developmental biology 17 35281087
2016 HSPA6 is an ulcerative colitis susceptibility factor that is induced by cigarette smoke and protects intestinal epithelial cells by stabilizing anti-apoptotic Bcl-XL. Biochimica et biophysica acta 17 26826017
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 Endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B') in human arterial smooth muscle cells. Nitric oxide : biology and chemistry 17 26656590
2019 HSPA6: A new autosomal recessive candidate gene for the VATER/VACTERL malformation spectrum. Birth defects research 16 30887706
2014 Antioxidant and HSP70B responses in Chlamydomonas reinhardtii genotypes with different resistance to oxidative stress. Ecotoxicology and environmental safety 15 24507138
2022 Re-sequencing of candidate genes FOXF1, HSPA6, HAAO, and KYNU in 522 individuals with VATER/VACTERL, VACTER/VACTERL-like association, and isolated anorectal malformation. Birth defects research 14 35362267
2022 N-Acetyl-L-Cysteine Protects Airway Epithelial Cells during Respiratory Syncytial Virus Infection against Mucin Synthesis, Oxidative Stress, and Inflammatory Response and Inhibits HSPA6 Expression. Analytical cellular pathology (Amsterdam) 14 36046596
2020 Significant reductions in apoptosis-related proteins (HSPA6, HSPA8, ITGB3, YWHAH, and PRDX6) are involved in immune thrombocytopenia. Journal of thrombosis and thrombolysis 13 33047245
2001 Repression of the HSP70B promoter by NFIL6, Ku70, and MAPK involves three complementary mechanisms. Biochemical and biophysical research communications 13 11162511
2022 High abundance of CDC45 inhibits cell proliferation through elevation of HSPA6. Cell proliferation 12 35642733
2023 PP4R1 accelerates the malignant progression of NSCLC via up-regulating HSPA6 expression and HSPA6-mediated ER stress. Biochimica et biophysica acta. Molecular cell research 11 37739270
2018 Study of the ichthyotoxic microalga Heterosigma akashiwo by transcriptional activation of sublethal marker Hsp70b in Transwell co-culture assays. PloS one 11 30071073
2019 Differential expression of HSF1 and HSPA6 genes and physiological responses in Angus and Simmental cattle breeds. Journal of thermal biology 10 31466795
2018 Transient Receptor Potential Channel A1 (TRPA1) Regulates Sulfur Mustard-Induced Expression of Heat Shock 70 kDa Protein 6 (HSPA6) In Vitro. Cells 10 30200301
2016 Targeting of Heat Shock Protein HSPA6 (HSP70B') to the Periphery of Nuclear Speckles is Disrupted by a Transcription Inhibitor Following Thermal Stress in Human Neuronal Cells. Neurochemical research 10 27743288
2008 Induction of the human heat shock promoter HSP70B by nutritional stress: implications for cancer gene therapy. Cancer investigation 10 18584345
2021 Long Noncoding RNA lnc-TSSK2-8 Activates Canonical Wnt/β-Catenin Signaling Through Small Heat Shock Proteins HSPA6 and CRYAB. Frontiers in cell and developmental biology 9 34041241
2012 Heat shock protein HSP70B as a marker for genotype resistance to environmental stress in Chlorella species from contrasting habitats. Gene 8 23246695
2021 Increased systemic HSP70B levels in spinal muscular atrophy infants. Annals of clinical and translational neurology 7 33991176
2023 BARX1 promotes osteosarcoma cell proliferation and invasion by regulating HSPA6 expression. Journal of orthopaedic surgery and research 5 36927457
2010 Reproducible fashion of the HSP70B' promoter-induced cytotoxic response on a live cell-based biosensor by cell cycle synchronization. Biotechnology and bioengineering 5 20552671
2023 ROR2 deficit may induce the tetralogy of Fallot via down-regulating of β-catenin/SOX3/HSPA6 in vitro and in vivo. Journal of cellular and molecular medicine 3 37749917
2026 Lactate promotes cuproptosis in acute kidney injury by activating H3K18 lactylation-dependent upregulation of HSPA6 expression. Life sciences 2 41616844
2025 A novel benzofuran derivative of β-elemene (ZT-22) inhibits hepatocellular carcinoma cell growth via directly targeting HSPA6. Chemico-biological interactions 2 40239884
2025 Carbonic Anhydrase IX Induces Human Osteosarcoma Cell Metastasis by Activating HSPA6 Expression Through the AMPK Signalling Pathway. Journal of cellular and molecular medicine 2 40765077
2025 TRIM35, a novel DNA-binding protein, epigenetically modifies H3 to promote HSPA6 transcription and suppress breast cancer progression. Cell death discovery 1 41136372
2026 Curcumin Protected CoCl2-Induced Apoptosis and Ferroptosis in Human Umbilical Vein Endothelial Cells by Regulating the Expression of HSPA6. Food science & nutrition 0 41502827
2026 HSPA6 is induced by RIG-I-like receptors and negatively regulates type-I interferon signaling. Cellular and molecular life sciences : CMLS 0 41762233
2026 HSPA6 Promotes Ferroptosis in Triple-Negative Breast Cancer by Rewiring Lipid Metabolism to Potentiate Membrane Lipid Peroxidation. International journal of biological sciences 0 42088412
2026 Hsa-miR-149-5p targets Men1 to inhibit the progression of gastric cancer through the HSPA6/JNK pathway. Cancer cell international 0 42092934
2026 HSPA6 maintains IMPDH2 phosphorylation to regulate GTP synthesis for driving radioresistance of glioblastoma stem cells. Cell reports 0 42234559
2025 CITED2 Binding to EP300 Regulates Human Spermatogonial Stem Cell Proliferation and Survival Through HSPA6. Stem cells international 0 40313859
2025 HSPB6 based on integrative multi-omics analysis can suppress colorectal cancer progression by downregulating HSPA6 expression through the JNK-JUND axis. Life sciences 0 41043501
2025 Exosome-derived Menin from cancer-associated fibroblasts promotes gastric cancer progression by activating the HSPA6/JNK/JunD pathway and inducing EMT. Journal of translational medicine 0 41353438
2025 PERP suppresses breast cancer metastasis via the ATF3-HSPA6 signaling pathway. The Journal of international medical research 0 41456178

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