Affinage

Showing HSPA8 — HSC70 is a alias.

HSPA8

Heat shock cognate 71 kDa protein · UniProt P11142

Length
646 aa
Mass
70.9 kDa
Annotated
2026-06-10
100 papers in source corpus 51 papers cited in narrative 52 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSPA8/Hsc70 is a constitutively expressed ATP-dependent molecular chaperone that uses cycles of nucleotide-driven substrate capture and release to protect, fold, traffic, and triage client proteins across the proteostasis network (PMID:7797540, PMID:29764935). Its substrate-binding domain engages short hydrophobic/aggregation-prone peptide motifs in the canonical DnaK-like cleft, which becomes rigidified upon client binding, while ATP hydrolysis in the nucleotide-binding domain powers the cycle and is reactivated by DnaJ co-chaperones (PMID:7797540, PMID:29764935, PMID:20363747); the Hsp110/Hsp105 family acts as a nucleotide exchange factor that drives ADP→ATP exchange through symmetric NBD bridging, and Hsp105α conversely inhibits Hsc70 ATPase activity to restrain the cycle (PMID:18550409, PMID:15292236). The chaperone cycle is directed toward distinct client fates by accessory factors: it cooperates with the E3 ligase CHIP to ubiquitinate clients such as phosphorylated tau and mutant SOD1 for proteasomal degradation, and CHIP can also ubiquitinate Hsc70 itself at multiple lysines (PMID:14612456, PMID:15198682, PMID:26010904); it engages BAG-family adaptors (BAG3, BAG5) to govern folding, sarcomeric protein localization, and substrate affinity (PMID:20884878, PMID:38454159); and it executes chaperone-mediated and endosomal-microautophagy by recognizing KFERQ-like motifs and delivering substrates to the lysosomal receptor LAMP2A (PMID:31346037, PMID:37973552, PMID:34942188, PMID:36182990). HSPA8 broadly controls the stability of folded and misfolded clients, acting both protectively—sequestering and inhibiting fibril formation of α-synuclein and tau and stabilizing cyclin D1/CDK4, Rab1A, and MYBPC3 (PMID:21832061, PMID:12588994, PMID:29298892, PMID:29875314, PMID:24801886)—and degradatively for CFTR, FSP27, PD-L1, and others, where the duration of the binding cycle determines pro-folding versus pro-degradation outcomes (PMID:21697503, PMID:38762492, PMID:25315694). Beyond classical chaperoning, HSPA8 acts as an ATP-powered 'amyloidase' that disassembles RHIM-domain functional amyloids (RIP1/RIP3/ZBP1/TRIF) independently of co-chaperones to suppress necroptosis, drives clathrin-coated vesicle uncoating with the J-domain cofactors auxilin/GAK, and chaperones mitochondrial carrier precursors to the Tom70 import receptor (PMID:17488288, PMID:19143589, PMID:37580406). Its activity is tuned by post-translational modifications including Mettl21c-mediated Lys-561 trimethylation (stabilizing and enhancing CMA), PRMT9-mediated arginine methylation, and nitric-oxide S-nitrosylation of the nucleotide-binding site (inhibitory) (PMID:31346037, PMID:30368041, PMID:37715221). Loss of hspa8 in zebrafish causes craniofacial and fin malformations through ER-stress activation of the Perk/eIF2α/Atf4 unfolded protein response, and TDP-43-mediated sequestration of HSPA8 mRNA disrupts synaptic vesicle endocytosis in motor neurons, linking the chaperone to development and neurodegeneration (PMID:28978466, PMID:36226668).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 High

    Established that Hsc70 is a bona fide ATP-dependent chaperone that protects and reactivates unfolded enzymes, defining its core biochemical activity and dependence on DnaJ co-chaperones.

    Evidence In vitro chaperone refolding/protection and ATPase assays on eukaryotic and prokaryotic enzyme substrates

    PMID:7797540

    Open questions at the time
    • Did not resolve atomic structure of substrate engagement
    • Species specificity mechanism (DnaK failure on eukaryotic substrates) not explained structurally
  2. 2003 High

    Connected Hsc70 to targeted protein degradation by showing it collaborates with the E3 ligase CHIP to recognize phospho-tau and route it for ubiquitination, defining a chaperone-to-proteasome triage axis.

    Evidence Co-IP, in vitro ubiquitination with CHIP/UbcH5B, and cell survival rescue

    PMID:14612456

    Open questions at the time
    • Did not define which Hsc70 conformational state recruits CHIP
    • In vivo relevance to tauopathy not established
  3. 2003 High

    Showed Hsc70 is a stable component of the active cyclin D1/CDK4 holoenzyme, extending its role from quality control to cell-cycle machinery assembly.

    Evidence Native complex affinity purification, co-IP, and kinase activity assay

    PMID:12588994

    Open questions at the time
    • Mechanism of cyclin D1 stabilization at the molecular level unresolved
    • Co-chaperone requirements not defined
  4. 2004 High

    Defined the negative regulatory limb of the cycle by showing Hsp105α inhibits Hsc70 ATPase activity, and demonstrated client selectivity for misfolded SOD1 feeding into CHIP-mediated degradation.

    Evidence In vitro ATPase/refolding assays with deletion mutants; co-IP and in vitro ubiquitination with mutant SOD1

    PMID:15198682 PMID:15292236

    Open questions at the time
    • How Hsc70 discriminates apo/reduced from metallated SOD1 not structurally defined
    • Physiological balance of Hsp105 inhibition vs Hsp110 exchange unclear
  5. 2007 High

    Mechanistically defined Hsc70's role in membrane traffic as the ATP-dependent clathrin-coated vesicle uncoating machine requiring J-domain cofactors auxilin/GAK.

    Evidence In vitro uncoating reconstitution plus genetic loss-of-function across organisms and imaging

    PMID:17488288

    Open questions at the time
    • Coupling of uncoating to subsequent clathrin recycling not fully resolved
    • Quantitative stoichiometry of Hsc70 on the cage incomplete
  6. 2008 High

    Solved the structural basis of nucleotide exchange, showing Hsp110 bridges nucleotides in both NBDs to drive ADP→ATP exchange and substrate release.

    Evidence X-ray crystallography of the Hsp110:Hsc70 complex with biochemical exchange assays and AUC

    PMID:18550409

    Open questions at the time
    • Did not capture the substrate-bound state coupled to exchange
    • Regulation of NEF choice in vivo unaddressed
  7. 2008 Medium

    Demonstrated that Hsc70 and Hsp72 cooperatively sustain HSP90 client stability and tumor-cell viability, establishing functional redundancy and cancer relevance.

    Evidence Dual siRNA knockdown with client immunoblot, cell-cycle and apoptosis readouts

    PMID:18772114

    Open questions at the time
    • Molecular link between Hsc70/Hsp72 and HSP90 not biochemically mapped
    • Tumor-specific dependency mechanism unresolved
  8. 2010 High

    Refined the chaperone-co-chaperone mechanism by showing DjA1 and Hsc70 bind distinct peptide sites on substrate simultaneously, challenging the canonical hand-off model, and revealed BAG3-directed CapZ delivery.

    Evidence SPR, cross-linking, peptide arrays; reciprocal co-IP and stretch assays in cardiomyocytes

    PMID:20363747 PMID:20884878

    Open questions at the time
    • Generality of independent-binding model beyond tested substrate unknown
    • How BAG3 selects CapZβ1 for delivery undefined
  9. 2011 High

    Established that the kinetics of the Hsc70 binding cycle (co-chaperone-controlled) decide client fate between folding and degradation, using CFTR and α-synuclein as test cases.

    Evidence Cell-free reconstituted translation with BAG-1 displacement and degradation assays; SPR/ThT aggregation and toxicity assays

    PMID:21697503 PMID:21832061

    Open questions at the time
    • Quantitative thresholds of cycle duration that switch fate not generalized
    • In vivo control of α-synuclein handling unestablished
  10. 2018 High

    Provided atomic-resolution evidence for substrate recognition, showing the substrate-binding domain is disordered until a tau-derived peptide binds the canonical cleft and rigidifies it; also distinguished Hsc70 fibril-end capping from small-HSP nucleation delay.

    Evidence NMR with NOE distance measurements, fluorescence competition, and ThT elongation assays

    PMID:29298892 PMID:29764935

    Open questions at the time
    • Full-length lid contribution to dynamics not resolved
    • Whether fibril capping operates in cells unproven
  11. 2018 High

    Linked HSPA8 to disease by showing TDP-43 sequesters its mRNA in motor neurons, disrupting the CSP/Hsc70 synaptic vesicle endocytosis complex across ALS models.

    Evidence Drosophila, mouse motor neuron, and human iPSC C9orf72 models with electrophysiology, imaging, and genetic rescue

    PMID:28978466

    Open questions at the time
    • Direct structural basis of TDP-43:HSPA8 mRNA interaction undefined
    • Therapeutic restoration of HSPA8 not tested clinically
  12. 2019 High

    Identified post-translational tuning of HSPA8 by Mettl21c-mediated Lys-561 trimethylation, which stabilizes the protein and enhances CMA of Mef2 transcription factors in slow muscle.

    Evidence In vitro methylation with MS site mapping and Mettl21c KO/knockin mice with CMA client readouts

    PMID:31346037

    Open questions at the time
    • How trimethylation alters HSPA8 turnover mechanistically unresolved
    • Tissue specificity of the modification not fully explained
  13. 2023 High

    Revealed a co-chaperone-independent 'amyloidase' activity in which HSPA8 disassembles RHIM functional amyloids via SBD motif recognition and NBD ATP hydrolysis to suppress necroptosis.

    Evidence In vitro amyloid disassembly, domain mutagenesis, motif mapping, cell and mouse necroptosis models

    PMID:37580406

    Open questions at the time
    • Whether other functional amyloids are substrates unknown
    • Regulation of this activity relative to canonical chaperoning unresolved
  14. 2024 High

    Expanded the BAG-adaptor repertoire by showing BAG5 enhances HSPA8 substrate affinity to fold sperm structural proteins, with loss causing acephalic spermatozoa syndrome.

    Evidence In vitro folding assay, co-IP, and BAG5 KO mice with sperm phenotyping

    PMID:38454159

    Open questions at the time
    • Mechanism by which BAG5 boosts affinity not structurally defined
    • Generality beyond SPATA6/motor protein clients unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HSPA8's many context-specific functions—degradation vs. protection, canonical chaperoning vs. amyloidase, and its numerous reported client interactions—are integrated and selected within a single cell remains unresolved.
  • No unified model explains co-chaperone/PTM-based switching among competing fates
  • Many partner interactions rest on single co-IP studies without structural or reciprocal validation
  • In vivo hierarchy of HSPA8 functions across tissues undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 5 GO:0140657 ATP-dependent activity 5 GO:0140096 catalytic activity, acting on a protein 4 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 3 GO:0005764 lysosome 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-9612973 Autophagy 4 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
BAG3BAG5DNAJA1/DJA1GAKHSPH1/HSP110LAMP2ASTUB1/CHIPTOMM70
Complex memberships
CHIP-Hsc70-BAG3 complexCSP/Hsc70 synaptic chaperone complexcyclin D1/CDK4 holoenzyme

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 HSPA8/Hsc70 binds phosphorylated tau, and this phosphorylation is a recognition requirement for ubiquitination of tau by the E3 ligase CHIP (with E2 enzyme UbcH5B); the CHIP-Hsc70 complex can rescue phosphorylated tau-induced cell death. Co-immunoprecipitation, in vitro ubiquitination assay, cell survival assay The Journal of biological chemistry High 14612456
2008 Crystal/cryo structure of the Hsp110:Hsc70 nucleotide exchange complex reveals that Hsp110 acts as a nucleotide exchange factor (NEF) for Hsc70 through extensive protein–protein interactions and symmetric bridging interactions between nucleotides bound in each partner's NBD, driving open-closed isomerization of the NBDs to promote ADP→ATP exchange. X-ray crystallography, biochemical nucleotide exchange assays, analytical ultracentrifugation Molecular cell High 18550409
2007 Hsc70 catalyzes ATP-dependent uncoating of clathrin-coated vesicles (CCVs) requiring J-domain cofactors auxilin or GAK; Hsc70 and auxilin are also required for clathrin exchange during coated-pit invagination and for chaperoning clathrin and adaptor proteins to enable formation of new CCPs. In vitro uncoating assays, genetic knockdown/knockout in multiple organisms, cell imaging Traffic (Copenhagen, Denmark) High 17488288
2004 Hsp/Hsc70 preferentially binds apo or reduced mutant SOD1 (but not metallated/oxidized SOD1); CHIP promotes polyubiquitination of Hsc70 when bound to mutant SOD1, and polyubiquitinated Hsc70 then interacts with the S5a subunit of the 26S proteasome in vitro to facilitate mutant SOD1 degradation. Co-immunoprecipitation, in vitro ubiquitination assay, pulldown with recombinant proteins Journal of neurochemistry High 15198682
2010 BAG3 promotes association between Hsc70 and the actin capping protein CapZβ1, facilitating CapZβ1 distribution to proper sarcomeric locations; loss of BAG3 or Hsc70 function leads to CapZ ubiquitin-proteasome-mediated degradation and myofibrillar disruption under mechanical stress. Co-immunoprecipitation, shRNA knockdown in rat neonatal cardiomyocytes, in vitro stretch assay, immunofluorescence Circulation research Medium 20884878
2011 Hsc70 sequesters soluble α-synuclein in an assembly-incompetent complex in the absence of ATP; ATP addition (with or without co-chaperones Hdj1/Hdj2) reduces Hsc70 affinity for soluble α-Syn and abolishes its assembly inhibition; Hsc70 binds α-Syn fibrils with ~5-fold higher affinity than soluble α-Syn and reduces fibril cellular toxicity. Surface plasmon resonance, fluorescence spectroscopy, thioflavin-T aggregation assay, cell toxicity assay The Journal of biological chemistry High 21832061
2011 Hsc70 binding cycle plays a dual role in CFTR fate: cotranslational Hsc70 binding is pro-folding, but posttranslational Hsc70 binding is essential for CFTR ubiquitination, ER dislocation, and proteasome-mediated degradation; this degradative function is highly sensitive to the duration of the Hsc70 binding cycle controlled by co-chaperones. Cell-free reconstituted translation system, BAG-1 C-terminal domain (CBag) to displace Hsc70, ubiquitination assay, pulse-chase degradation assay Molecular biology of the cell High 21697503
2003 Hsc70 associates with newly synthesized cyclin D1 and remains a component of the mature, catalytically active cyclin D1/CDK4 holoenzyme; Hsc70 promotes stabilization of newly synthesized cyclin D1 and ensures formation of a catalytically active complex with CDK4 and Cip/Kip proteins. Affinity chromatography purification of native complexes, co-immunoprecipitation, kinase activity assay Molecular and cellular biology High 12588994
2004 Hsp105α suppresses Hsc70 chaperone activity by inhibiting Hsc70 ATPase activity; interaction between Hsp105α and Hsc70 (mapped via deletion mutants of both proteins) is necessary for this inhibition; Hsp105α is thereby a negative regulator of the Hsc70 chaperone substrate-binding cycle. In vitro ATPase assay, chaperone refolding assay, deletion mutagenesis, co-immunoprecipitation The Journal of biological chemistry High 15292236
1995 Hsc70 protects and reactivates heat-inactivated eukaryotic (DNA polymerases α and ε) and prokaryotic enzymes in an ATP hydrolysis-dependent manner; addition of a DnaJ homologue reduces the amount of Hsc70 required for reactivation ~10-fold; DnaK cannot reactivate eukaryotic enzymes, showing species specificity. In vitro chaperone refolding/protection assay, ATPase assay, antibody-based purification The Journal of biological chemistry High 7797540
1995 Hsc70 co-immunoprecipitates with all three polyomavirus capsid proteins (VP1, VP2, VP3) in vivo during infection; hsc70 subcellular location shifts from cytoplasmic to nuclear coincident with nuclear localization of capsid proteins; this association likely prevents premature cytosolic capsid assembly and/or facilitates nuclear transport. Co-immunoprecipitation, indirect immunofluorescence, in vitro translation Journal of virology Medium 7494292
2009 Hsc70 (along with Hsp90) complexes with mitochondrial carrier precursors in the cytosol and interacts specifically with the Tom70 import receptor to promote mitochondrial import; deletion of the PiC presequence reduced Hsc70 binding and reduced Hsc70 dependence for import without affecting Hsp90. Co-immunoprecipitation, in vitro import assay, deletion mutagenesis, DHFR fusion protein binding The Biochemical journal Medium 19143589
2017 TDP-43 overexpression sequesters Hsc70-4/HSPA8 mRNA and impairs its translation in motor neurons, reducing HSPA8 protein at the NMJ; this disrupts the synaptic CSP/Hsc70 chaperone complex, impairing dynamin function and synaptic vesicle endocytosis; overexpression of Hsc70-4, CSP, or dynamin partially restores function. Drosophila ALS model, electrophysiology, imaging, genetic interaction/epistasis, primary mouse motor neurons, human iPSC C9orf72 models Cell reports High 28978466
2018 Hsc70 inhibits tau fibril elongation (possibly by capping fibril ends) through tight binding to aggregation-prone motifs in the microtubule-binding repeat region under aggregation-promoting conditions; this mechanism is distinct from HspB1, which delays nucleation by weak transient interactions with early aggregation species. Fluorescence spectroscopy, NMR spectroscopy, thioflavin-T fibril elongation assay The Journal of biological chemistry High 29298892
2018 NMR mapping shows Hsc70 BETA construct (substrate-binding domain without lid) is dynamically disordered in the absence of substrate; binding of the Tau sequence GKVQIINKKG (Kd ~500 nM) causes dramatic rigidification; NOE measurements confirm binding occurs in the canonical substrate-binding cleft analogous to DnaK. NMR spectroscopy (NOE measurements), fluorescence competition assay, in vitro chaperone activity assay The Journal of biological chemistry High 29764935
2015 CHIP ubiquitinates Hsc70 and Hsp70 at multiple (but different) lysine residues; proteomic analysis identified 16 ubiquitinated lysines in Hsc70 out of 45 detectable, including K159 uniquely ubiquitinated in Hsc70 but not Hsp70; CHIP generates multiple Ub chain types with E2 enzymes UbcH5a and Ube2W differently, and Ube2W predominantly targets the N-terminal amine. In vitro ubiquitination assay, mass spectrometry, K-R ubiquitin mutant analysis PloS one High 26010904
2019 Mettl21c trimethylates Hsc70/Hspa8 at Lys-561, enhancing its stability; this modification promotes Hspa8 function in chaperone-mediated autophagy, leading to degradation of client transcription factors Mef2A and Mef2D in type I muscle fibers. Co-immunoprecipitation, mass spectrometry, in vitro methylation assay, Mettl21c knockout mice, immunoblot The Journal of biological chemistry High 31346037
2018 Nitric oxide S-nitrosylates Hsc70/HSPA8 within its nucleotide-binding site, impairing its function in protein folding, organelle import/export, and chaperone-mediated LAMP2a-dependent autophagy (CMA); this contributes to accumulation of CMA substrates and loss of LAMP2a. Redox proteomics (SNO-trap), deep proteome analysis, autophagy/CMA assays, nNOS-overexpressing neuronal cell line Redox biology Medium 30368041
2023 HSPA8 acts as an 'amyloidase' that directly disassembles RHIM-containing functional amyloids (RIP1, RIP3, ZBP1, TRIF) to inhibit necroptosis; HSPA8 recognizes RHIM-containing proteins via a hydrophobic hexapeptide motif N(X1)φ(X3) through its SBD domain to prevent fibril stacking, and uses its NBD domain ATP hydrolysis energy to break down pre-formed RHIM-amyloids into non-functional monomers; this activity does not require the co-chaperone system. In vitro amyloid disaggregation assay, cell-based necroptosis assays, mutagenesis, domain mapping, mouse model Cell research High 37580406
2024 Hsc70 binds PD-L1 directly and promotes its degradation through the endosome-lysosome pathway; Hsc70-PD-L1 binding inhibits the CMTM6-PD-L1 interaction, reducing PD-L1 recycling to the cell membrane; Hsc70 overexpression reduces tumor PD-L1 expression and inhibits tumor growth in vivo. Co-immunoprecipitation, flow cytometry, xenograft mouse model, Hsc70 overexpression/knockdown Nature communications Medium 38762492
2023 PRMT9 methylates HSPA8 at arginine residues R76 and R100, enhancing its function in suppressing ferroptosis in HCC; this methylation upregulates CD44 expression downstream of HSPA8, which mediates ferroptosis inhibition; HBx promotes this pathway by inducing PRMT9 expression. Co-immunoprecipitation, mass spectrometry identification of methylation sites, in vitro ferroptosis assays, in vivo mouse HCC model Journal of translational medicine Medium 37715221
2023 HSPA8 promotes CMA-dependent degradation of caveolin-1 (CAV1) by directly interacting with the KFERQ-like (KIFSN) motif on CAV1; p38 MAPK-mediated phosphorylation of CAV1 at S168 enhances this interaction; CAV1 degradation releases β-catenin into the nucleus to activate Wnt/β-catenin signaling. Co-immunoprecipitation, CMA assay, mutagenesis, phosphorylation analysis, mouse xenograft Advanced science Medium 37973552
2023 HSPA8 physically binds RHOB (residues 1–42 and 89–118) and BECN1 (ECD domain) via its NBD and LID domains, preventing their degradation; HSPA8 contains intrinsically disordered regions and drives liquid-liquid phase separation to concentrate RHOB and BECN1 into liquid droplets, promoting anti-bacterial autophagy. Co-immunoprecipitation, domain deletion mapping, LLPS assays (droplet formation imaging), bacterial clearance assay Autophagy Medium 37312409
2008 Simultaneous silencing of both HSC70 (HSPA8) and HSP72 (but not either alone) induces proteasome-dependent degradation of HSP90 client proteins, G1 cell-cycle arrest, and tumor-specific apoptosis, indicating both isoforms cooperatively support HSP90 function in cancer cells. siRNA dual knockdown, immunoblot for HSP90 clients, flow cytometry (cell cycle), apoptosis assay Cancer cell Medium 18772114
2008 Hsc70 silencing increases ASIC2 cell surface expression and inhibits vascular smooth muscle cell (VSMC) migration; this inhibition is abolished by co-silencing ASIC2, indicating Hsc70 normally retains ASIC2 intracellularly and its removal allows surface ASIC2 to inhibit VSMC migration. siRNA knockdown, cell surface biotinylation assay, chemotaxis migration assay American journal of physiology. Heart and circulatory physiology Medium 18310515
2010 Multiple Hsc70 molecules and a DjA1 dimer bind independently to an unfolded protein substrate; Hsc70 binding involves a conformational change and is faster than DjA1 binding; DjA1 binds in a bivalent, substoichiometric manner to distinct peptide sequences from those recognized by Hsc70, arguing against the canonical model that DnaJ-bound substrate is transferred to Hsp70. Surface plasmon resonance, gel filtration, chemical cross-linking, peptide array binding The Journal of biological chemistry High 20363747
2021 LAMP2A cytoplasmic tail directly crosslinks to Hsc70 in cells (demonstrating a direct interaction); truncation of the membrane-distal lumenal domain of LAMP2A reduces Hsc70 co-immunoprecipitation, showing that LAMP2A's two-domain lumenal architecture regulates its interaction with Hsc70 at the lysosome cytoplasmic surface. Site-specific photo-crosslinking in cells, co-immunoprecipitation with truncation mutants Experimental cell research Medium 34942188
2019 Mettl21c-mediated Lys-561 trimethylation of Hspa8 stabilizes the protein in type I muscle fibers; Mettl21c knockout reduces Hspa8 trimethylation and protein levels in slow muscles, and Mettl21c overexpression increases them; stabilized Hspa8 enhances CMA-mediated degradation of Mef2A and Mef2D. Co-immunoprecipitation, mass spectrometry, in vitro methylation assay, Mettl21c-LacZ knockin and KO mouse models The Journal of biological chemistry High 31346037
2013 HSC71/Hsc70 interacts with VISA (MAVS) and negatively regulates virus-triggered VISA aggregation; overexpression of HSC71 potently inhibits virus-triggered IFNB1 transcription and antiviral response, while HSC71 knockdown has opposite effects. Co-immunoprecipitation, overexpression and siRNA knockdown, VISA aggregation assay, luciferase reporter (IFNB1) Protein & cell Medium 23636689
2004 Gentamicin specifically binds to the C-terminal (peptide-binding domain) of HSP73/Hsc70, induces a conformational change (CD spectrum), and suppresses its chaperone activity (prevention of rhodanese aggregation) in vitro; HSP73 and gentamicin co-localize in enlarged lysosomes of rat kidneys with GM-induced tubular injury in vivo. GM-affinity column purification, CD spectroscopy, chaperone activity assay (rhodanese aggregation), limited proteolysis mapping, immunohistochemistry The Journal of biological chemistry High 14966137
2018 HSC70 is a chaperone for both wild-type and mutant MYBPC3; HSC70 knockdown slows degradation of both WT and mutant MYBPC3, while pharmacologic activation of HSC70/HSP70 accelerates degradation; HSC70 localizes in discrete sarcomeric striations. Unbiased co-immunoprecipitation/mass spectrometry, siRNA knockdown, pharmacologic activation, pulse-chase degradation assay, immunofluorescence JCI insight High 29875314
2018 Nuclear export of HSPA8 after heat shock is required for cell survival; blocking HSPA8 egress from nucleus to cytoplasm during recovery (using the P140 phosphopeptide) prevents its redistribution and impairs cell survival under secondary oxidative stress; crosslinking-proteomics shows P140 binds regions near nuclear import and export signal sequences of HSPA8. P140 peptide treatment, immunofluorescence, crosslinking-proteomics, cell survival assay under sequential stresses Scientific reports Medium 30429537
2000 By immunogold electron microscopy, HSP73 (HSPA8) is distributed throughout nonstressed cells with predominant cytoplasmic localization associated with mitochondria, and relocalizes to nuclei, nucleoli, and cytoplasm (with increased mitochondrial label) after heat stress; this is distinct from HSP72 which is primarily nuclear under non-stress conditions. Immunogold electron microscopy, indirect immunohistochemistry The journal of histochemistry and cytochemistry Medium 10681386
2008 HSPA8 protein from oviductal epithelium binds to spermatozoa surface and enhances sperm survival at 39°C; antibody pre-treatment of the HSPA8-containing fraction reduces the survival-enhancing effect, and recombinant bovine HSPA8 (0.5–2 µg/ml) recapitulates the dose-responsive sperm survival effect in both boar and bull spermatozoa. Proteomic identification, antibody neutralization assay, recombinant protein supplementation, sperm viability assay Reproduction (Cambridge, England) Medium 18996976
2022 HSPA8 interacts with PRRSV glycoprotein 4 (GP4) via its carboxy-terminal peptide-binding (PB) domain; HSPA8 facilitates PRRSV attachment and is required for clathrin-dependent endocytosis-mediated internalization; inhibition of HSPA8 ATPase activity reduces CME efficiency and PRRSV infection. Co-immunoprecipitation, domain truncation, antibody neutralization assay, siRNA knockdown, ATPase inhibitor treatment, viral titer/RNA assay Microbiology spectrum Medium 35138165
2017 Hsc70 regulates EV-A71 IRES activity: Hsc70 binds viral genomic RNA and interacts with 2A protease, promoting eIF4G cleavage; knockdown reduces IRES activity and viral replication while overexpression enhances them; Hsc70 inhibitor Ver-155008 suppresses IRES activity and viral replication dose-dependently. siRNA knockdown, Hsc70 overexpression, IRES-luciferase reporter assay, RNA immunoprecipitation, co-immunoprecipitation (2A protease), viral replication assay, inhibitor treatment Antiviral research Medium 29180285
2016 BAG3, together with Hsc70, promotes formation of a CHIP-Hsc70-BAG3 complex; STAT5-dependent transcriptional upregulation of HSPA8 in CML drives nuclear translocation and stabilization of the cyclin D1/CDK4 complex, contributing to CML cell proliferation. Chromatin immunoprecipitation (STAT5), nuclear fractionation, co-immunoprecipitation (HSPA8-CCND1), specific HSP inhibitor (15-deoxyspergualin) cell viability assay British journal of haematology Medium 18537972
2014 Hsc70 prevents stress-induced degradation of Rab1A by binding it in a chaperone-dependent manner; Hsc70 knockdown decreases Rab1A protein levels and increases Rab1A ubiquitination under stress; Rab1A knockdown causes cell death by inhibiting autophagosome formation. Mass spectrometry-based proteomics with anti-Hsc70 affinity purification, co-immunoprecipitation, siRNA knockdown, ubiquitination assay, autophagy assay PloS one Medium 24801886
2014 HSC70 interacts with the FSP27 protein; HSC70 knockdown increases FSP27 half-life under AMPK-activating conditions; CHIP knockdown did not alter FSP27 stability, indicating CHIP is not the relevant E3 ligase in this context; AMPK promotes FSP27 ubiquitination and proteasomal degradation in an HSC70-dependent manner. Mass spectrometry, co-immunoprecipitation, siRNA knockdown, CHX chase assay, AICAR/phenformin treatment American journal of physiology. Endocrinology and metabolism Medium 25315694
2021 HSPA8 interacts with negatively charged phospholipids (phosphatidylserine and cardiolipin) with high selectivity and low affinity for phosphatidylcholine; membrane insertion is spontaneous, entropy-driven, and diminished by ADP or ATP; HSPA8 can carry HSP90 (which lacks intrinsic lipid binding) into lipid bilayers. In vitro lipid binding assay, thermodynamic analysis, membrane insertion assay Cell stress & chaperones Medium 34003451
2016 MNSFβ noncovalently binds to HSPA8 in the presence of ATP in vitro; double knockdown of MNSFβ and HSPA8 strongly inhibits RANKL-induced osteoclastogenesis, ERK1/2 and p38 phosphorylation, and TNFα production in Raw264.7 cells. MALDI-TOF MS, in vitro binding assay, double siRNA knockdown, RANKL differentiation assay, immunoblot Molecular and cellular biochemistry Medium 27581120
2022 Genetic deletion of hspa8 in zebrafish using CRISPR/Cas9 causes malformations of pharyngeal arches, pectoral fins, head, and eyes; pharyngeal arch deficiency is caused by induction of ER stress and activation of the Perk/p-eIF2α/Atf4 unfolded protein response pathway; inhibition of Perk/p-eIF2α/Atf4 rescues pharyngeal arch development. CRISPR/Cas9 knockout zebrafish, immunoblot (UPR markers), Perk inhibitor rescue experiment Journal of cell science High 36226668
2019 HSPA8 co-immunoprecipitates with CLCN2 in rat PV cardiomyocytes; co-expression of HSPA8 with CLCN2 shifts its voltage-dependent activation curve to negative potentials with increasing [Cl⁻], converting CLCN2 current properties to match the native hyperpolarization-activated Cl⁻ current (ICl,h) in PV cardiomyocytes. Mass spectrometry identification, co-immunoprecipitation, whole-cell patch-clamp electrophysiology, HSPA8+CLCN2 co-expression in HEK293/PC12 cells, molecular docking The Journal of biological chemistry Medium 31506297
2019 EF1A1 and HSC70 interact (identified by co-immunoprecipitation/MS); knockdown of either EF1A1 or HSC70 increases OGD-induced apoptosis of brain vascular endothelial cells by enhancing JNK pathway activation (increased p-JNK, p-cJUN, cleaved caspase-9/3); a JNK inhibitor rescues this phenotype. Co-immunoprecipitation with mass spectrometry, siRNA knockdown, Annexin V apoptosis assay, immunoblot, JNK inhibitor rescue CNS neuroscience & therapeutics Medium 27324700
2024 BAG5 forms a complex with HSPA8 and promotes protein folding of SPATA6 (and myosin/dynein proteins) by enhancing HSPA8's substrate affinity; BAG5 knockout leads to HTCA assembly defects, acephalic spermatozoa syndrome, and male infertility in mice. Co-immunoprecipitation, in vitro protein folding assay, BAG5 KO mice, immunofluorescence, sperm phenotype analysis EMBO reports High 38454159
2024 HSPA8 suppresses NLRP3 inflammasome-mediated pyroptosis by maintaining levels of SKP2 (an E3 ubiquitin ligase); when HSPA8 is suppressed, SKP2 is degraded, reducing NLRP3 ubiquitination and promoting its activation to drive pyroptosis in alveolar epithelial cells in sepsis-induced lung injury. siRNA knockdown, overexpression (AAV9-SKP2), mouse CLP sepsis model, immunoblot, flow cytometry (pyroptosis markers) Cell & bioscience Medium 38698431
2023 HSPA8 enhances HBV replication by recruiting hepatitis B core protein (HBc) to the HBV cccDNA minichromosome; HSPA8 suppresses ferroptosis in liver cancer by upregulating SLC7A11/GPX4 and decreasing erastin-induced ROS and Fe²⁺ accumulation. Co-immunoprecipitation (HSPA8-HBc), chromatin immunoprecipitation (HBc on cccDNA), siRNA knockdown, in vitro ferroptosis assays, xenograft mouse model Cancer research Medium 36745032
2023 HSPA8 interacts with ALDH2 in mitochondria after oxygen-glucose deprivation (OGD); HSPA8 translocates to mitochondria under OGD and binding to ALDH2 inhibits its enzyme activity; HSPA8 siRNA knockdown restores ALDH2 activity and alleviates OGD-induced fibroblast senescence. Co-immunoprecipitation with mass spectrometry, ALDH2 enzyme activity assay, siRNA knockdown, senescence assays Antioxidants (Basel, Switzerland) Medium 38247467
2024 HSPA8 directly binds CLPP protein and regulates its stability; HSPA8 promotes CLPP degradation, which in turn controls mitophagy levels and cisplatin resistance in ovarian cancer cells; overexpression of CLPP reverses the pro-mitophagy and resistance effects of HSPA8. Co-immunoprecipitation, protein stability assay, siRNA/overexpression, mitophagy assays (immunofluorescence), IC50 measurement Acta biochimica et biophysica Sinica Low 38419499
2019 GKN2 directly interacts with Hsc70 and promotes ROS-induced apoptosis through inhibition of NF-κB and activation of JNK signaling; inhibition of GKN2-Hsc70 interaction attenuates GKN2-induced effects. Co-immunoprecipitation, overexpression, siRNA inhibition of interaction, NF-κB and JNK pathway immunoblot, apoptosis assay Journal of experimental & clinical cancer research Low 31382983
2021 Hsc70 mediates endosomal microautophagy and chaperone-mediated autophagy of oxidized PRL2, promoting its degradation under oxidative/inflammatory conditions; PRL2 degradation drives osteoclast differentiation and bone destruction; hydroxychloroquine (autophagy inhibitor) blocks inflammation-induced PRL2 degradation in vivo. Co-immunoprecipitation, CMA/eMI assay, mouse models (PRL2 KO, arthritis), hydroxychloroquine treatment Cell death and differentiation Medium 36182990
2025 Pristimerin directly binds HSPA8 (confirmed by DARTS, CETSA, and SPR) and promotes its ubiquitination and degradation; this leads to accumulation of VAV1 (a client protein stabilized by HSPA8), activating the ERK pathway and inducing autophagy and apoptosis in TNBC cells. Drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), surface plasmon resonance, ubiquitination assay, RNA sequencing, siRNA knockdown Advanced science Medium 39813169

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival. The Journal of biological chemistry 391 14612456
2013 HSPA8/HSC70 chaperone protein: structure, function, and chemical targeting. Autophagy 333 24121476
2008 Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosis. Cancer cell 269 18772114
2012 Comprehensive review on the HSC70 functions, interactions with related molecules and involvement in clinical diseases and therapeutic potential. Pharmacology & therapeutics 222 22960394
2008 Structure of the Hsp110:Hsc70 nucleotide exchange machine. Molecular cell 180 18550409
2007 Multiple roles of auxilin and hsc70 in clathrin-mediated endocytosis. Traffic (Copenhagen, Denmark) 175 17488288
2004 CHIP promotes proteasomal degradation of familial ALS-linked mutant SOD1 by ubiquitinating Hsp/Hsc70. Journal of neurochemistry 153 15198682
2010 BAG3 and Hsc70 interact with actin capping protein CapZ to maintain myofibrillar integrity under mechanical stress. Circulation research 122 20884878
2019 HSPA8/HSC70 in Immune Disorders: A Molecular Rheostat that Adjusts Chaperone-Mediated Autophagy Substrates. Cells 115 31394830
2011 Hsc70 protein interaction with soluble and fibrillar alpha-synuclein. The Journal of biological chemistry 103 21832061
2023 HBx-Induced HSPA8 Stimulates HBV Replication and Suppresses Ferroptosis to Support Liver Cancer Progression. Cancer research 90 36745032
1995 In vivo and in vitro association of hsc70 with polyomavirus capsid proteins. Journal of virology 86 7494292
2017 Post-transcriptional Inhibition of Hsc70-4/HSPA8 Expression Leads to Synaptic Vesicle Cycling Defects in Multiple Models of ALS. Cell reports 84 28978466
2008 Effects of HSPA8, an evolutionarily conserved oviductal protein, on boar and bull spermatozoa. Reproduction (Cambridge, England) 82 18996976
2018 HspB1 and Hsc70 chaperones engage distinct tau species and have different inhibitory effects on amyloid formation. The Journal of biological chemistry 76 29298892
2003 Hsc70 regulates accumulation of cyclin D1 and cyclin D1-dependent protein kinase. Molecular and cellular biology 73 12588994
2005 Treatment with extracellular HSP70/HSC70 protein can reduce polyglutamine toxicity and aggregation. Journal of neurochemistry 71 15992387
1992 Molecular cloning and characterization of a constitutively expressed heat-shock-cognate hsc71 gene from rainbow trout. European journal of biochemistry 62 1371753
2016 CaM/BAG5/Hsc70 signaling complex dynamically regulates leaf senescence. Scientific reports 53 27539741
2014 Analysis of HSPA8 and HSPA9 mRNA expression and promoter methylation in the brain and blood of Alzheimer's disease patients. Journal of Alzheimer's disease : JAD 50 23948933
1989 Heat-shock cognate protein (hsc71) and related proteins in mouse spermatogenic cells. Biology of reproduction 50 2665832
2014 Inhibition of nestin suppresses stem cell phenotype of glioblastomas through the alteration of post-translational modification of heat shock protein HSPA8/HSC71. Cancer letters 48 25527454
2009 Mitochondrial carrier protein biogenesis: role of the chaperones Hsc70 and Hsp90. The Biochemical journal 48 19143589
2018 Expression of HSP90AA1/HSPA8 in hepatocellular carcinoma patients with depression. OncoTargets and therapy 47 29872313
2004 Hsp105alpha suppresses Hsc70 chaperone activity by inhibiting Hsc70 ATPase activity. The Journal of biological chemistry 45 15292236
2021 Similarities and Differences of Hsp70, hsc70, Grp78 and Mortalin as Cancer Biomarkers and Drug Targets. Cells 43 34831218
2020 Mechanism and Complex Roles of HSC70 in Viral Infections. Frontiers in microbiology 42 32849328
2011 Role of Hsc70 binding cycle in CFTR folding and endoplasmic reticulum-associated degradation. Molecular biology of the cell 41 21697503
2024 Hsc70 promotes anti-tumor immunity by targeting PD-L1 for lysosomal degradation. Nature communications 39 38762492
2020 Targeting Hsc70-based autophagy to eliminate amyloid β oligomers. Biochemical and biophysical research communications 39 32057360
2000 Heat-induced alterations in the localization of HSP72 and HSP73 as measured by indirect immunohistochemistry and immunogold electron microscopy. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 39 10681386
2021 High HSPA8 expression predicts adverse outcomes of acute myeloid leukemia. BMC cancer 38 33926391
2023 Arginine methylation of HSPA8 by PRMT9 inhibits ferroptosis to accelerate hepatitis B virus-associated hepatocellular carcinoma progression. Journal of translational medicine 36 37715221
2016 Rotenone down-regulates HSPA8/hsc70 chaperone protein in vitro: A new possible toxic mechanism contributing to Parkinson's disease. Neurotoxicology 36 27133439
2008 Hsc70 regulates cell surface ASIC2 expression and vascular smooth muscle cell migration. American journal of physiology. Heart and circulatory physiology 36 18310515
1995 Calf thymus Hsc70 protein protects and reactivates prokaryotic and eukaryotic enzymes. The Journal of biological chemistry 36 7797540
2023 HSPA8 Activates Wnt/β-Catenin Signaling to Facilitate BRAF V600E Colorectal Cancer Progression by CMA-Mediated CAV1 Degradation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 35 37973552
2018 The disorderly conduct of Hsc70 and its interaction with the Alzheimer's-related Tau protein. The Journal of biological chemistry 35 29764935
2014 Hsc70 contributes to cancer cell survival by preventing Rab1A degradation under stress conditions. PloS one 35 24801886
2022 Long noncoding RNA MAGI2-AS3 regulates the H2O2 level and cell senescence via HSPA8. Redox biology 34 35797800
2019 Physicochemical changes in liver and Hsc70 expression in pikeperch Sander lucioperca under heat stress. Ecotoxicology and environmental safety 34 31176247
2017 Hsc70 regulates the IRES activity and serves as an antiviral target of enterovirus A71 infection. Antiviral research 34 29180285
2015 A central role for HSC70 in regulating antigen trafficking and MHC class II presentation. Molecular immunology 34 25953005
2019 miR-26b-5p helps in EpCAM+cancer stem cells maintenance via HSC71/HSPA8 and augments malignant features in HCC. Liver international : official journal of the International Association for the Study of the Liver 33 31276277
2008 BCR-ABL1-induced expression of HSPA8 promotes cell survival in chronic myeloid leukaemia. British journal of haematology 32 18537972
2018 Nitric oxide contributes to protein homeostasis by S-nitrosylations of the chaperone HSPA8 and the ubiquitin ligase UBE2D. Redox biology 31 30368041
2023 HSPA8 acts as an amyloidase to suppress necroptosis by inhibiting and reversing functional amyloid formation. Cell research 30 37580406
2022 Heat Shock Protein Member 8 (HSPA8) Is Involved in Porcine Reproductive and Respiratory Syndrome Virus Attachment and Internalization. Microbiology spectrum 30 35138165
2022 Inhibition of HSPA8 by rifampicin contributes to ferroptosis via enhancing autophagy. Liver international : official journal of the International Association for the Study of the Liver 30 36254713
2016 EF1A1/HSC70 Cooperatively Suppress Brain Endothelial Cell Apoptosis via Regulating JNK Activity. CNS neuroscience & therapeutics 30 27324700
1995 Localization of the gene encoding the human heat shock cognate protein, HSP73, to chromosome 11. Genomics 30 8530083
2017 Enhanced tau pathology via RanBP9 and Hsp90/Hsc70 chaperone complexes. Human molecular genetics 29 29016855
2015 Biochemical and Proteomic Analysis of Ubiquitination of Hsc70 and Hsp70 by the E3 Ligase CHIP. PloS one 29 26010904
2018 HSC70 is a chaperone for wild-type and mutant cardiac myosin binding protein C. JCI insight 28 29875314
2018 Blocking nuclear export of HSPA8 after heat shock stress severely alters cell survival. Scientific reports 28 30429537
1997 Stress protein (hsp73)-mediated, TAP-independent processing of endogenous, truncated SV40 large T antigen for Db-restricted peptide presentation. European journal of immunology 28 9295040
2023 HSPA8 regulates anti-bacterial autophagy through liquid-liquid phase separation. Autophagy 27 37312409
2019 Overexpression of Hsc70 promotes proliferation, migration, and invasion of human glioma cells. Journal of cellular biochemistry 27 30816582
2004 73-kDa molecular chaperone HSP73 is a direct target of antibiotic gentamicin. The Journal of biological chemistry 26 14966137
2019 Methyltransferase-like 21c methylates and stabilizes the heat shock protein Hspa8 in type I myofibers in mice. The Journal of biological chemistry 25 31346037
2001 Genomic cloning of the Hsc71 gene in the hermaphroditic teleost Rivulus marmoratus and analysis of its expression in skeletal muscle: identification of a novel muscle-preferred regulatory element. Nucleic acids research 25 11452029
2015 Hypoxia induced altered expression of heat shock protein genes (Hsc71, Hsp90α and Hsp10) in Indian Catfish, Clarias batrachus (Linnaeus, 1758) under oxidative stress. Molecular biology reports 24 25663092
2004 Expression of HSP70/HSC70 in swine blastocysts: effects of oxidative and thermal stress. Molecular reproduction and development 24 15349842
2021 Human heat shock cognate protein (HSC70/HSPA8) interacts with negatively charged phospholipids by a different mechanism than other HSP70s and brings HSP90 into membranes. Cell stress & chaperones 23 34003451
2010 Multiple molecules of Hsc70 and a dimer of DjA1 independently bind to an unfolded protein. The Journal of biological chemistry 23 20363747
2023 Macrophage-Specific NLRC5 Protects From Cardiac Remodeling Through Interaction With HSPA8. JACC. Basic to translational science 22 37325412
2020 HSPA8 knock-down induces the accumulation of neurodegenerative disorder-associated proteins. Neuroscience letters 22 32712350
2019 HSC70 expression is reduced in lymphomonocytes of sporadic ALS patients and contributes to TDP-43 accumulation. Amyotrophic lateral sclerosis & frontotemporal degeneration 22 31663379
2019 GKN2 promotes oxidative stress-induced gastric cancer cell apoptosis via the Hsc70 pathway. Journal of experimental & clinical cancer research : CR 21 31382983
1993 An immunoassay for heat shock protein 73/72: use of the assay to correlate HSP73/72 levels in mammalian cells with heat response. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 20 8366304
2024 The novel lnc-HZ12 suppresses autophagy degradation of BBC3 by preventing its interactions with HSPA8 to induce trophoblast cell apoptosis. Autophagy 19 38836496
2022 HSC70 mediated autophagic degradation of oxidized PRL2 is responsible for osteoclastogenesis and inflammatory bone destruction. Cell death and differentiation 19 36182990
2021 The two-domain architecture of LAMP2A regulates its interaction with Hsc70. Experimental cell research 19 34942188
2016 Ubiquitin-like protein MNSFβ noncovalently binds to molecular chaperone HSPA8 and regulates osteoclastogenesis. Molecular and cellular biochemistry 19 27581120
2014 The critical roles of HSC70 in physiological and pathological processes. Current pharmaceutical design 19 23944377
1999 Characterization and expression of the mouse Hsc70 gene. Biochimica et biophysica acta 19 10095055
2012 Matrine modulates HSC70 levels and rescues ΔF508-CFTR. Journal of cellular physiology 18 22170045
2023 The TGEV Membrane Protein Interacts with HSC70 To Direct Virus Internalization through Clathrin-Mediated Endocytosis. Journal of virology 17 36975782
2021 Deacetylation of HSC70-4 Promotes Bombyx mori Nucleopolyhedrovirus Proliferation via Proteasome-Mediated Nuclear Import. Frontiers in physiology 17 33679433
2014 Regulation of FSP27 protein stability by AMPK and HSC70. American journal of physiology. Endocrinology and metabolism 17 25315694
2016 A novel heat shock protein alpha 8 (Hspa8) molecular network mediating responses to stress- and ethanol-related behaviors. Neurogenetics 16 26780340
2024 BAG5 regulates HSPA8-mediated protein folding required for sperm head-tail coupling apparatus assembly. EMBO reports 15 38454159
2017 Rabies viruses leader RNA interacts with host Hsc70 and inhibits virus replication. Oncotarget 15 28388579
2015 iTRAQ-Based Quantitative Proteomic Analysis Identified HSC71 as a Novel Serum Biomarker for Renal Cell Carcinoma. BioMed research international 15 26425554
2013 Heat shock cognate 71 (HSC71) regulates cellular antiviral response by impairing formation of VISA aggregates. Protein & cell 15 23636689
1997 Induction of Hsp72 and transient nuclear localization of Hsp73 and Hsp72 correlate with the acquisition and loss of thermotolerance in postimplantation rat embryos. Developmental dynamics : an official publication of the American Association of Anatomists 15 9022060
2024 Raltitrexed induces apoptosis through activating ROS-mediated ER stress by impeding HSPA8 expression in prostate cancer cells. Biochimica et biophysica acta. Molecular cell research 14 38301906
2024 The suppression of HSPA8 attenuates NLRP3 ubiquitination through SKP2 to promote pyroptosis in sepsis-induced lung injury. Cell & bioscience 14 38698431
2013 Esophageal cancer alters the expression of nuclear pore complex binding protein Hsc70 and eIF5A-1. Functional & integrative genomics 14 23539416
1997 Association of HSP73 with the acquired resistance to uranyl acetate-induced acute renal failure. Toxicology 14 9057897
2023 The Binding of HSPA8 and Mitochondrial ALDH2 Mediates Oxygen-Glucose Deprivation-Induced Fibroblast Senescence. Antioxidants (Basel, Switzerland) 13 38247467
2022 Genetic deletion of hspa8 leads to selective tissue malformations in zebrafish embryonic development. Journal of cell science 13 36226668
2019 Molecular identification of HSPA8 as an accessory protein of a hyperpolarization-activated chloride channel from rat pulmonary vein cardiomyocytes. The Journal of biological chemistry 13 31506297
2016 Functional analysis of HSPA1A and HSPA8 in parturition. Biochemical and biophysical research communications 13 28025138
2012 Psychotropics regulate Skp1a, Aldh1a1, and Hspa8 transcription--potential to delay Parkinson's disease. Progress in neuro-psychopharmacology & biological psychiatry 13 23046827
2006 Cell death and expression of heat-shock protein Hsc70 in the hyperthermic rat brain. Journal of neurochemistry 13 16635260
2025 Pristimerin Promotes Ubiquitination of HSPA8 and Activates the VAV1/ERK Pathway to Suppress TNBC Proliferation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 39813169
2024 HSPA8-mediated stability of the CLPP protein regulates mitochondrial autophagy in cisplatin-resistant ovarian cancer cells. Acta biochimica et biophysica Sinica 12 38419499
2021 Molecular mapping of platelet hyperreactivity in diabetes: the stress proteins complex HSPA8/Hsp90/CSK2α and platelet aggregation in diabetic and normal platelets. Translational research : the journal of laboratory and clinical medicine 12 33887528
2020 HSC70 is required for infectious bursal disease virus (IBDV) infection in DF-1 cells. Virology journal 12 32375812

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