Affinage

Showing HSPD1 — HSP60 is a alias.

HSPD1

60 kDa heat shock protein, mitochondrial · UniProt P10809

Length
573 aa
Mass
61.1 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSPD1 (HSP60) is a mitochondrial chaperonin that uses ATP binding and hydrolysis, together with the co-chaperonin HSP10, to encapsulate non-native polypeptides and promote their refolding (PMID:9759498, PMID:26427351, PMID:29415503). Mammalian HSP60 differs mechanistically from bacterial GroEL: cryo-EM and biochemical reconstitution show it exists predominantly as single-ring heptamers in the apo state and transitions to football-type double-ring complexes upon ATP and HSP10 binding, dissociating back to single rings after ATP hydrolysis (PMID:26427351, PMID:29415503, PMID:33506187), and it possesses GTPase as well as ATPase activity (PMID:29208924). Assembly of newly imported HSP60 subunits into oligomeric complexes is itself catalyzed by pre-existing functional HSP60 in an ATP-dependent manner (PMID:1978929). Functionally, HSP60 is required to fold mitochondrial clients including manganese superoxide dismutase, and its loss elevates oxidative stress and protein aggregation, defining it as a central node of mitochondrial protein quality control (PMID:24151936, PMID:28196897). HSP60 is essential for early mouse embryonic development (PMID:20393889), and missense mutations (V72I/V98I) that reduce its ATPase and refolding activity cause SPG13 hereditary spastic paraplegia (PMID:11898127, PMID:18400758). Beyond mitochondrial proteostasis, cytosolic and extracellular pools of HSP60 modulate apoptosis by stabilizing mitochondrial survivin and restraining p53 (PMID:18086682), promote tumor cell metastasis through beta-catenin (PMID:19369584), and facilitate interferon-beta induction via IRF3 (PMID:25506707). Multiple small molecules (gold-1a, myrtucommulone A, arsenic trioxide, KHS101) directly bind HSP60 and inhibit its refolding activity, and HSPD1 supports cancer cell oxidative phosphorylation and proliferation (PMID:26663758, PMID:34476069, PMID:34364401).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1990 High

    Established that HSP60 oligomer assembly is autocatalytic, addressing how imported subunits acquire their functional double-ring architecture.

    Evidence Yeast mif4 mutant with in vitro mitochondrial import and pulse-chase subunit assembly analysis

    PMID:1978929

    Open questions at the time
    • Did not resolve the structural intermediate of assembly
    • Mammalian assembly pathway not directly tested
  2. 1992 Low

    First report that cytosolic/mitochondrial HSP60 physically associates with a signaling GTPase (p21ras), an early hint of roles beyond canonical folding.

    Evidence Chemical cross-linking and Co-IP in mammalian cells

    PMID:1347942

    Open questions at the time
    • Single cross-linking/Co-IP method without reciprocal validation
    • Functional significance of the interaction not established
  3. 1998 High

    Defined the chaperonin reaction cycle mechanistically, showing how ATP and GroES drive encapsulation and timed release of folding substrates.

    Evidence Crystal structures of GroEL-GroES complexes plus in vitro ATPase and folding assays

    PMID:9759498

    Open questions at the time
    • Based on bacterial GroEL; mammalian HSP60 cycle differences not yet defined
    • Native substrate repertoire not characterized
  4. 2002 High

    Linked HSPD1 to a human Mendelian disease, showing a missense mutation impairs essential chaperonin function.

    Evidence Family linkage mapping and E. coli groES/groEL complementation assay of wild-type vs V72I HSP60

    PMID:11898127

    Open questions at the time
    • Did not quantify the biochemical defect of the mutant
    • Neuronal pathophysiology not addressed
  5. 2005 Medium

    Extended HSP60 function to apoptosis regulation and to interaction with the mortalin chaperone, indicating cytosolic and cross-chaperone roles.

    Evidence Co-IP, subcellular fractionation, siRNA knockdown and microscopy in cardiac and tumor cells

    PMID:15784164 PMID:15957980

    Open questions at the time
    • Single-lab Co-IP without structural mapping of Bax/Bak binding
    • Mechanism of hypoxia-induced redistribution unresolved
  6. 2007 Medium

    Showed HSP60 stabilizes mitochondrial survivin and restrains p53, defining a cyto-protective apoptotic node in tumor cells, and identified a non-classical exosomal secretion route.

    Evidence siRNA ablation with reciprocal Co-IP, apoptosis flow cytometry, and exosome fractionation

    PMID:17307989 PMID:18086682

    Open questions at the time
    • Whether survivin/p53 binding is direct or chaperone-mediated unclear
    • Trigger for exosomal release not defined
  7. 2008 High

    Resolved the molecular basis of SPG13 by showing the V98I mutation reduces ATPase and refolding activity and acts dominant-negatively.

    Evidence In vitro ATPase and malate dehydrogenase refolding assays plus bacterial conditional-expression model; patient-cell protease expression analysis

    PMID:18378094 PMID:18400758

    Open questions at the time
    • Compensatory Lon/ClpP downregulation is correlative (Low confidence)
    • Link from folding defect to motor neuron degeneration not mechanistically traced
  8. 2008 Medium

    Identified an upstream transcriptional driver, showing c-MYC activates HSP60 to support oncogenic transformation.

    Evidence E-box promoter luciferase reporter, ChIP, and siRNA rescue of focus formation

    PMID:19022255

    Open questions at the time
    • Other transcriptional inputs not mapped
    • Single-lab evidence
  9. 2009 Medium

    Broadened cytosolic HSP60 functions to beta-catenin-driven metastasis and YB-1 distribution control.

    Evidence Co-IP with domain mapping, overexpression/siDNA epistasis, invasion and mouse metastasis assays; sucrose-gradient analysis of YB-1

    PMID:19369584 PMID:19470374

    Open questions at the time
    • Mechanism of proteasome-independent beta-catenin stabilization unresolved
    • Single-lab Co-IPs
  10. 2010 High

    Established HSP60 as essential for early mammalian development through clean genetic ablation.

    Evidence Gene-trap homozygous Hspd1 knockout mice with embryo staging

    PMID:20393889

    Open questions at the time
    • Specific lethal cellular defect not identified
    • Tissue-specific roles not dissected
  11. 2013 Medium

    Connected HSP60 chaperone activity to redox homeostasis via MnSOD folding and defined extracellular HSP60 as a TLR4 inflammatory ligand.

    Evidence Heterozygous Hspd1 KO mice with Hsp60-MnSOD Co-IP and oxidative stress assays; exogenous HSP60 with pathway inhibitors and rat LAD ligation

    PMID:23447644 PMID:24151936

    Open questions at the time
    • Whether MnSOD misfolding fully explains neuronal oxidative stress untested
    • Receptor specificity of secreted HSP60 vs endotoxin contamination concern
  12. 2014 Medium

    Placed HSP60 in innate antiviral signaling upstream of IRF3 phosphorylation.

    Evidence Co-IP, gain/loss of function, IFN-beta reporter and SeV infection, with epistasis against constitutively active IRF3

    PMID:25506707

    Open questions at the time
    • Direct enzymatic role in IRF3 activation not defined
    • Single-lab evidence
  13. 2015 Medium

    Implicated HSP60 in mitochondrial trafficking of the disease protein FUS, linking it to neurodegeneration models.

    Evidence Co-IP and Drosophila genetic knockdown with mitochondrial fractionation and phenotype rescue

    PMID:26335776

    Open questions at the time
    • Whether HSP60 directly imports FUS or chaperones it is unresolved
    • Mammalian relevance not tested
  14. 2017 High

    Refined the mammalian chaperonin cycle and revealed an intrinsic GTPase activity, distinguishing HSP60 from GroEL.

    Evidence TEM, native PAGE, gel filtration and refolding assays with purified porcine HSP60; in vitro nucleotide hydrolysis assays

    PMID:26427351 PMID:29208924 PMID:29415503

    Open questions at the time
    • Physiological role of GTPase activity in cells untested
    • Structural basis of the single/double-ring switch not resolved here
  15. 2017 Medium

    Defined HSP60 as a central protein-quality-control node in renal tubular cells under metabolic stress.

    Evidence siRNA knockdown with aggregation, ATP, and oxidized-protein assays; miR-382/HSPD1 manipulation in UUO mouse model

    PMID:28196897 PMID:28680529

    Open questions at the time
    • Direct client proteins driving aggregation not identified
    • Single-lab in vivo data
  16. 2020 High

    Provided high-resolution structural confirmation that human HSPD1 adopts single-ring architecture distinct from GroEL.

    Evidence Cryo-EM structure of apo human HSPD1

    PMID:33506187

    Open questions at the time
    • Substrate-bound and HSP10-bound states not resolved in this work
    • Functional consequence of apical-domain flexibility untested
  17. 2021 High

    Validated HSP60 as a druggable target whose inhibition disrupts apoptotic complexes and oxidative phosphorylation in cancer.

    Evidence Metalloproteomic and chemical-probe target ID (arsenic trioxide), CRISPR/siRNA with Seahorse flux and genome-wide screen (KHS101) in NSCLC and APL

    PMID:34364401 PMID:34476069

    Open questions at the time
    • Selectivity of inhibitors over other chaperones incompletely defined
    • Mechanistic link between OXPHOS collapse and HSP60 folding clients not fully mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the mammalian single-ring/double-ring cycle and GTPase activity select and process specific endogenous mitochondrial clients, and how moonlighting cytosolic/extracellular HSP60 functions mechanistically relate to its chaperonin activity, remain unresolved.
  • No comprehensive endogenous substrate map
  • Direct vs chaperone-mediated nature of cytosolic interactions unresolved
  • Structural basis of GTP-dependent allostery undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 5 GO:0044183 protein folding chaperone 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0003924 GTPase activity 1
Localization
GO:0005739 mitochondrion 5 GO:0005576 extracellular region 3 GO:0005829 cytosol 3 GO:0005886 plasma membrane 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1266738 Developmental Biology 1
Partners
BIRC5CTNNB1FUSHSPA9HSPE1IRF3SOD2TP53
Complex memberships
HSP60/HSP10 (HSPD1/HSPE1) chaperonin

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 GroEL (HSP60) mediates protein folding through major asymmetric conformational changes driven by ATP binding and GroES co-chaperonin interaction. A nonnative polypeptide bound to one GroEL ring is encapsulated by GroES to form a cis ternary complex, initiating folding in a sequestered cavity; ATP hydrolysis in the cis ring primes product release, and subsequent ATP binding in the trans ring disrupts the cis complex, allowing the polypeptide to achieve its native state or recycle. Structural and biochemical reconstitution studies; crystal structures of GroEL-GroES complexes; in vitro ATPase and folding assays Annual review of biochemistry High 9759498
1990 HSP60 monomers require pre-existing functional HSP60 complex for their own assembly into 14-mer double-ring complexes after import into mitochondria. In hsp60-defective yeast (mif4 mutant), newly imported wild-type subunits fail to assemble, demonstrating that self-assembly of HSP60 is catalyzed by existing HSP60 complex in an ATP-dependent process. Yeast genetic mutant (mif4), in vitro mitochondrial import assay, pulse-chase analysis of subunit assembly Nature High 1978929
2002 The V72I (p.Val98Ile in updated nomenclature) missense mutation in human HSPD1 causes SPG13 hereditary spastic paraplegia. Wild-type HSP60 together with co-chaperonin HSP10 can complement E. coli cells lacking groEL/groES, but HSP60(V72I) cannot, demonstrating the mutation impairs essential chaperonin function. Genetic complementation assay in E. coli groES/groEL deletion strain; family linkage mapping American journal of human genetics High 11898127
2007 HSP60 is released from adult cardiac myocytes via the exosomal pathway. Within exosomes, HSP60 is tightly attached to the exosome membrane rather than being free in the lumen. Exosome isolation, Western blot, investigation of multiple secretion pathways including classical Golgi-mediated pathway American journal of physiology. Heart and circulatory physiology Medium 17307989
2007 HSP60 regulates tumor cell apoptosis by stabilizing mitochondrial survivin and restraining p53 function. Acute siRNA ablation of HSP60 destabilizes mitochondrial survivin, induces mitochondrial dysfunction, disrupts an HSP60-p53 complex (leading to p53 stabilization), increases Bax expression, and activates caspase-dependent apoptosis. siRNA knockdown, high-throughput proteomics (co-IP screen), Co-immunoprecipitation, flow cytometry for apoptosis, Western blot The Journal of biological chemistry High 18086682
2005 Cytosolic HSP60 in cardiac cells complexes with pro-apoptotic proteins Bax and Bak and with Bcl-XL, but not with Bcl-2. During hypoxia, HSP60 redistributes from cytosol to the plasma membrane. Reduction in HSP60 expression precipitates apoptosis without altering mitochondrial function, and HSP60 accelerates cleavage of pro-caspase-3. Co-immunoprecipitation, subcellular fractionation, siRNA knockdown, Western blot, live-cell imaging Journal of cellular and molecular medicine Medium 15784164
2008 The SPG13-associated HSP60 mutation p.V98I (c.292G>A) reduces ATPase activity and strongly decreases capacity to refold denatured malate dehydrogenase in vitro. In a bacterial model lacking endogenous chaperonin genes, expression of Hsp60(V98I)/Hsp10 strongly inhibits cell growth. Co-expression of mutant and wild-type Hsp60 at low levels produces a dominant negative effect. In vitro ATPase assay, in vitro malate dehydrogenase refolding assay, bacterial complementation model with conditional gene expression, microarray analysis The Journal of biological chemistry High 18400758
2009 HSP60 interacts with beta-catenin through its apical domain, increases beta-catenin protein levels, and enhances beta-catenin transcriptional activity to promote metastasis. siRNA-mediated repression of beta-catenin reverts the metastatic activity caused by HSP60 overexpression. Proteasomal activity is not required for HSP60-induced beta-catenin increase. Co-immunoprecipitation, overexpression/siRNA knockdown, in vitro invasion assays, mouse in vivo metastasis model Carcinogenesis Medium 19369584
2013 Extracellular HSP60 induces inflammatory cytokine production in cardiomyocytes via TLR4-MyD88-p38-NF-κB pathway, and upregulates TLR2/4 expression via TLR4-MyD88-JNK-NF-κB pathway. During ischemia, endogenous HSP60 is released extracellularly and activates the same pathways. Exogenous HSP60 treatment of cardiomyocytes, siRNA/pathway inhibitors, in vivo rat LAD ligation model, ELISA, Western blot Cardiovascular research Medium 23447644
2005 HSP60 and mortalin (mtHsp70) physically interact both in vivo and in vitro, with the N-terminal region of mortalin involved in the interaction. They show co- and exclusive localizations in vivo, and both are involved in tumorigenesis, but mortalin (not HSP60) overexpression extends in vitro lifespan of normal fibroblasts. Co-immunoprecipitation, in vitro pulldown, shRNA knockdown, fluorescence microscopy co-localization, in vitro lifespan assay The Biochemical journal Medium 15957980
2013 The Hsp60 folding machinery is required for proper folding of manganese superoxide dismutase (MnSOD). Hsp60 and MnSOD physically interact. In heterozygous Hspd1 knockout mice (modeling SPG13), decreased Hsp60 leads to increased oxidative stress in neuronal tissues, attributed to impaired MnSOD folding. Heterozygous Hspd1 knockout mouse model, co-immunoprecipitation of Hsp60-MnSOD, oxidative stress measurements, enzyme activity assays Free radical research Medium 24151936
2010 Homozygous inactivation of Hspd1 (gene-trap insertion) causes early embryonic lethality in mice at days 6.5–7.5 post-implantation, demonstrating that Hsp60 is essential for early embryonic development. Heterozygous mice survive normally with reduced Hsp60 and Hsp10 protein levels. Gene-trap mouse knockout, Western blot, qRT-PCR, embryo staging Cell stress & chaperones High 20393889
2014 HSPD1 (HSP60) interacts with IRF3 and facilitates interferon-beta induction. HSPD1 overexpression promotes IRF3 phosphorylation and dimerization and enhances IFN-β production upon SeV infection; HSPD1 knockdown inhibits this pathway. HSPD1 acts upstream of IRF3 phosphorylation (it does not enhance activity of constitutively active IRF3/5D). Co-immunoprecipitation, overexpression and siRNA knockdown, luciferase reporter assays, SeV infection, Western blot for IRF3 phosphorylation PloS one Medium 25506707
2015 FUS physically interacts with HSP60, and FUS translocation to mitochondria is mediated at least in part by HSP60. Downregulating HSP60 in Drosophila reduces mitochondrially localized FUS and partially rescues mitochondrial defects and neurodegenerative phenotypes caused by FUS overexpression. Biochemical interaction assays (Co-IP), Drosophila genetic model with HSP60 knockdown, mitochondrial fractionation, neurodegenerative phenotype assessment PLoS genetics Medium 26335776
2015 Gold(III) meso-tetraphenylporphyrin (gold-1a) directly targets HSP60 and inhibits its chaperonin refolding activity. Multiple chemical biology approaches (photo-affinity labeling, click chemistry, chemical proteomics, cellular thermal shift assay, STD-NMR, protein fluorescence quenching, chaperone assays) established HSP60 as the direct molecular target of the compound both in vitro and in cells. Photo-affinity labeling, click chemistry, chemical proteomics, cellular thermal shift assay, saturation-transfer difference NMR, protein fluorescence quenching, protein chaperone refolding assays Angewandte Chemie (International ed. in English) High 26663758
2017 Myrtucommulone A (MC) directly binds HSP60 and inhibits its chaperonin refolding activity. MC prevents HSP60-mediated reactivation of denatured malate dehydrogenase. HSP60 inhibition by MC causes aggregation of Lon protease (LONP) and LRP130 in isolated mitochondria under heat shock. Protein fishing/pulldown with MC as bait from mitochondrial lysates, in vitro protein refolding assay (malate dehydrogenase), 2D gel electrophoresis identification of aggregating proteins Cell chemical biology Medium 28457707
2017 Mammalian HSP60 possesses GTPase activity in addition to ATPase activity. The presence of GTP differently affects HSP60 allostery, complex formation with HSP10, and protein folding activity compared to ATP. GTP slightly affects the ATPase activity of HSP60 during protein folding. In vitro nucleotide hydrolysis assays, HSP60/HSP10 complex formation assays, protein refolding assays Scientific reports Medium 29208924
2018 Mammalian HSP60 exists predominantly as single-ring heptamers in the absence of co-chaperonin HSP10. In the presence of ATP and HSP10, HSP60 forms mainly football-type double-ring complexes and mediates substrate refolding. After ATP hydrolysis to ADP, HSP60 releases HSP10 and double rings dissociate to single rings. This ATP-dependent single-ring/double-ring transition is distinct from the GroEL/GroES bacterial cycle. Transmission electron microscopy, native PAGE, gel filtration, in vitro refolding assay with purified porcine HSP60 Archives of biochemistry and biophysics / International journal of molecular sciences High 26427351 29415503
2020 Cryo-EM structure of human mitochondrial HSPD1 in the apo state reveals that, unlike bacterial GroEL, HSPD1 forms mostly single-ring assemblies in the absence of co-chaperonin HSPE1. Comparison with GroEL shows rotation and increased flexibility of the apical domain in HSPD1. Cryo-electron microscopy (cryo-EM) structural determination iScience High 33506187
1992 HSP60 (chaperonin) physically associates with p21ras in mammalian cells. This interaction was detected by chemical cross-linking and verified as physiological by showing that the amount of HSP60 complexed with p21ras did not change upon overexpression of p21ras. Chemical cross-linking, co-immunoprecipitation, protein purification, partial amino acid sequencing, cDNA cloning Proceedings of the National Academy of Sciences of the United States of America Low 1347942
2009 HSP60 interacts with YB-1 at the YB-NLS region in the cytoplasm. Suppression of HSP60 expression increases polysome-associated YB-1 in heavy-sedimenting fractions. Overexpression of HSP60 decreases YB-1 in heavy-sedimenting fractions and suppresses YB-NLS nuclear localization signal activity. Thus HSP60 acts as a regulator of YB-1 polysome association and subcellular distribution. Co-immunoprecipitation, sucrose gradient sedimentation, overexpression and siRNA knockdown, nuclear localization assays Biochemical and biophysical research communications Medium 19470374
2006 Extracellular HSP60 binds to the surface of antigen-presenting cells (macrophages and dendritic cells, but not T or B lymphocytes) and co-localizes with LPS co-receptor CD14. HSP60 specifically binds bacterial LPS and synergistically enhances IL-12p40 production and IFN-γ release in T cells in combination with LPS. HSP60 also induces IFN-α production in professional APC, independently of LPS. Binding assays (flow cytometry), co-localization microscopy, cytokine ELISA, IFN-α neutralization, IFN receptor knockout cells The Journal of biological chemistry Medium 17164250
2021 Arsenic trioxide (ATO) directly binds HSP60 and abolishes its refolding capability. ATO binding to HSP60 disrupts HSP60-p53 and HSP60-survivin complexes, resulting in degradation of p53 and survivin in APL cells. Organoarsenic affinity probe (metalloproteomics), quantitative proteomics, cellular thermal shift assay, biophysical binding assays, cell-based apoptosis assays Chemical science High 34476069
2021 HSPD1 knockdown or chemical disruption by KHS101 induces a drastic breakdown of oxidative phosphorylation and suppresses NSCLC cell proliferation in vitro and in vivo. HSPD1-targeted anti-cancer effects are dependent on oxidative phosphorylation, with creatine-transporter SLC6A8 and cytochrome c oxidase subunit COX5B identified as molecular determinants of sensitivity. CRISPR/Cas9 knockout, siRNA knockdown, extracellular metabolic flux analysis (Seahorse), whole-genome CRISPR screen, drug profiling, transcriptomics, in vivo xenograft Journal of experimental & clinical cancer research High 34364401
2017 HSP60 (HSPD1) knockdown in renal tubular cells increases intracellular protein aggregates, alters intracellular ATP production (increases ATP), and markedly increases oxidized proteins (under normoglycemic conditions). Under hyperglycemia, HSP60 levels increase and regulate oxidative stress responses, indicating HSP60 is a central node in protein quality control in renal tubular cells. siRNA knockdown, protein aggregation assay, luciferin-luciferase ATP assay, OxyBlot oxidized protein assay, global protein network analysis FASEB journal Medium 28196897
2017 miR-382 targets HSPD1 (HSP60) mRNA, reducing HSP60 protein levels, which contributes to redox imbalance and renal tubulointerstitial fibrosis. HSPD1 overexpression restores thioredoxin (Trx) expression and reverses TGF-β1-induced loss of E-cadherin; direct siRNA knockdown of HSPD1 in vivo promotes oxidative stress. miR-382 anti-miRNA treatment in UUO mouse model, siRNA knockdown in vivo, HSPD1 overexpression in vitro, luciferase 3'UTR reporter (implied), Western blot, oxidative stress markers Oxidative medicine and cellular longevity Medium 28680529
2008 Decreased expression of mitochondrial proteases Lon and ClpP is observed in SPG13 patient cells expressing HSP60(p.V98I), at both RNA and protein levels. This is proposed as a cellular adaptation to reduced chaperonin activity that allows more folding attempts for substrate proteins. Lymphoblastoid and fibroblast cells from SPG13 patient, qRT-PCR, Western blot, mitochondrial membrane potential assay, cell viability assay Neuroscience Low 18378094
2008 c-MYC directly activates HSP60 transcription by binding an E-box (CACGTG) site in the proximal HSP60 promoter. siRNA-mediated repression of HSP60 reduces c-MYC-induced cellular transformation. Promoter luciferase reporter assay, chromatin immunoprecipitation (implied), siRNA knockdown, focus formation assay FEBS letters Medium 19022255

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Structure and function in GroEL-mediated protein folding. Annual review of biochemistry 436 9759498
1997 GroEL-mediated protein folding. Protein science : a publication of the Protein Society 313 9098884
2007 HSP60 trafficking in adult cardiac myocytes: role of the exosomal pathway. American journal of physiology. Heart and circulatory physiology 300 17307989
2002 Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. American journal of human genetics 268 11898127
1995 Evolution of the chaperonin families (Hsp60, Hsp10 and Tcp-1) of proteins and the origin of eukaryotic cells. Molecular microbiology 230 7752884
2007 Hsp60 regulation of tumor cell apoptosis. The Journal of biological chemistry 223 18086682
2001 GroEL (Hsp60) of Clostridium difficile is involved in cell adherence. Microbiology (Reading, England) 174 11160803
1990 The mitochondrial chaperonin hsp60 is required for its own assembly. Nature 169 1978929
2013 Cardiac myocyte exosomes: stability, HSP60, and proteomics. American journal of physiology. Heart and circulatory physiology 165 23376832
1993 Sequence homologies between hsp60 and autoantigens. Immunology today 163 8466626
2015 FUS Interacts with HSP60 to Promote Mitochondrial Damage. PLoS genetics 155 26335776
2005 HSP60, Bax, apoptosis and the heart. Journal of cellular and molecular medicine 145 15784164
2012 Structure and allostery of the chaperonin GroEL. Journal of molecular biology 143 23183375
2006 GroEL-mediated protein folding: making the impossible, possible. Critical reviews in biochemistry and molecular biology 123 16849107
2020 Hsp60 Post-translational Modifications: Functional and Pathological Consequences. Frontiers in molecular biosciences 112 32582761
2009 Interaction between HSP60 and beta-catenin promotes metastasis. Carcinogenesis 101 19369584
2013 Extracellular HSP60 induces inflammation through activating and up-regulating TLRs in cardiomyocytes. Cardiovascular research 98 23447644
2015 Anticancer Gold(III) Porphyrins Target Mitochondrial Chaperone Hsp60. Angewandte Chemie (International ed. in English) 94 26663758
2018 Toward Developing Chemical Modulators of Hsp60 as Potential Therapeutics. Frontiers in molecular biosciences 87 29732373
2005 Identification and characterization of molecular interactions between mortalin/mtHsp70 and HSP60. The Biochemical journal 82 15957980
2020 Understanding GroEL and DnaK Stress Response Proteins as Antigens for Bacterial Diseases. Vaccines 75 33348708
2004 Expansion and compression of a protein folding intermediate by GroEL. Molecular cell 75 15469819
2004 GroEL mediates protein folding with a two successive timer mechanism. Molecular cell 74 15149592
2010 Inactivation of the hereditary spastic paraplegia-associated Hspd1 gene encoding the Hsp60 chaperone results in early embryonic lethality in mice. Cell stress & chaperones 71 20393889
2008 Decreased expression of the mitochondrial matrix proteases Lon and ClpP in cells from a patient with hereditary spastic paraplegia (SPG13). Neuroscience 68 18378094
2006 Synergistic and differential modulation of immune responses by Hsp60 and lipopolysaccharide. The Journal of biological chemistry 68 17164250
2003 Overexpression of PHGPx and HSP60/10 protects against ischemia/reoxygenation injury. Free radical biology & medicine 67 14583338
2014 Formation and structures of GroEL:GroES2 chaperonin footballs, the protein-folding functional form. Proceedings of the National Academy of Sciences of the United States of America 64 25136110
2024 Molecular Chaperonin HSP60: Current Understanding and Future Prospects. International journal of molecular sciences 62 38791521
2008 The Hsp60-(p.V98I) mutation associated with hereditary spastic paraplegia SPG13 compromises chaperonin function both in vitro and in vivo. The Journal of biological chemistry 61 18400758
2019 Functional Compartmentalization of HSP60-Survivin Interaction between Mitochondria and Cytosol in Cancer Cells. Cells 60 31861751
2011 Hsp60 and heme oxygenase-1 (Hsp32) in acute myocardial infarction. Translational research : the journal of laboratory and clinical medicine 59 21497776
1992 An interaction between p21ras and heat shock protein hsp60, a chaperonin. Proceedings of the National Academy of Sciences of the United States of America 57 1347942
1994 Subcellular localization and chaperone activities of Borrelia burgdorferi Hsp60 and Hsp70. Journal of bacteriology 55 7961395
2007 Expression of Hsp60 and Grp78 in the human endometrium and oviduct, and their effect on sperm functions. Human reproduction (Oxford, England) 54 17670764
2022 The multiple roles and therapeutic potential of HSP60 in cancer. Biochemical pharmacology 53 35609646
1991 Involvement of GroEL in nif gene regulation and nitrogenase assembly. Journal of bacteriology 53 1680848
2014 Versatile roles of the chaperonin GroEL in microorganism-insect interactions. FEMS microbiology letters 52 24460534
2017 Mitochondrial Chaperonin HSP60 Is the Apoptosis-Related Target for Myrtucommulone. Cell chemical biology 51 28457707
1998 GroEL under heat-shock. Switching from a folding to a storing function. The Journal of biological chemistry 51 9829996
2013 The Hsp60 folding machinery is crucial for manganese superoxide dismutase folding and function. Free radical research 48 24151936
2016 Does Hsp60 Provide a Link between Mitochondrial Stress and Inflammation in Diabetes Mellitus? Journal of diabetes research 47 27478851
2016 Disease-Associated Mutations in the HSPD1 Gene Encoding the Large Subunit of the Mitochondrial HSP60/HSP10 Chaperonin Complex. Frontiers in molecular biosciences 47 27630992
2021 Lactobacillus stress protein GroEL prevents colonic inflammation. Journal of gastroenterology 45 33782752
2019 Hsp60 and IL-8 axis promotes apoptosis resistance in cancer. British journal of cancer 45 31673102
2018 GroEL Ring Separation and Exchange in the Chaperonin Reaction. Cell 45 29336887
2017 Role of HSP60 (HSPD1) in diabetes-induced renal tubular dysfunction: regulation of intracellular protein aggregation, ATP production, and oxidative stress. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 45 28196897
2009 Localization of Hsp60 and Grp78 in the human testis, epididymis and mature spermatozoa. International journal of andrology 45 19207617
2004 HSP60 induces self-tolerance to repeated HSP60 stimulation and cross-tolerance to other pro-inflammatory stimuli. European journal of immunology 45 15214052
1992 Induction of human hsp60 expression in monocytic cell lines. International immunology 45 1567788
2007 A novel mutation in the HSPD1 gene in a patient with hereditary spastic paraplegia. Journal of neurology 43 17420924
2001 groEL encodes a highly antigenic protein in Burkholderia pseudomallei. Clinical and diagnostic laboratory immunology 43 11427437
2017 Microglia activation triggers oligodendrocyte precursor cells apoptosis via HSP60. Molecular medicine reports 42 28586011
2013 Hyperglycaemia and oxidative stress upregulate HSP60 & HSP70 expression in HeLa cells. SpringerPlus 41 24058891
1997 Structural and mechanistic consequences of polypeptide binding by GroEL. Folding & design 41 9427006
2021 Metabolic impairment of non-small cell lung cancers by mitochondrial HSPD1 targeting. Journal of experimental & clinical cancer research : CR 40 34364401
2009 Immunogenicity and protective efficacy of GroEL (hsp60) of Streptococcus pneumoniae against lethal infection in mice. FEMS immunology and medical microbiology 40 19484809
2021 Arsenic trioxide targets Hsp60, triggering degradation of p53 and survivin. Chemical science 39 34476069
2016 GroEL/ES inhibitors as potential antibiotics. Bioorganic & medicinal chemistry letters 39 27184767
2012 What distinguishes GroEL substrates from other Escherichia coli proteins? The FEBS journal 39 22177460
2018 Physicochemical Properties of the Mammalian Molecular Chaperone HSP60. International journal of molecular sciences 36 29415503
2017 HSP60 possesses a GTPase activity and mediates protein folding with HSP10. Scientific reports 36 29208924
2003 Differentiation of rickettsiae by groEL gene analysis. Journal of clinical microbiology 36 12843026
2019 Iterative annealing mechanism explains the functions of the GroEL and RNA chaperones. Protein science : a publication of the Protein Society 35 31800116
2015 Reaction Cycle of Chaperonin GroEL via Symmetric "Football" Intermediate. Journal of molecular biology 33 25900372
2012 Molecular chaperone disorders: defective Hsp60 in neurodegeneration. Current topics in medicinal chemistry 32 23339303
2008 HSP60 as a target of anti-ergotypic regulatory T cells. PloS one 32 19107191
2007 NO-induced downregulation of HSP10 and HSP60 expression in the postischemic brain. Journal of neuroscience research 32 17348040
2020 Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells. International journal of molecular sciences 31 31963896
2019 CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells. International journal of molecular sciences 31 30609639
2006 GroEL: More than Just a folding cage. Cell 31 16751091
2018 Inhibiting expression of HSP60 and TLR4 attenuates paraquat-induced microglial inflammation. Chemico-biological interactions 30 30584891
2010 Loss and gain of GroEL in the Mollicutes. Biochemistry and cell biology = Biochimie et biologie cellulaire 30 20453921
2008 Direct regulation of HSP60 expression by c-MYC induces transformation. FEBS letters 30 19022255
2018 Folding of maltose binding protein outside of and in GroEL. Proceedings of the National Academy of Sciences of the United States of America 29 29295923
2020 Cryo-EM structure of human mitochondrial HSPD1. iScience 28 33506187
2015 Functional structure and physiological functions of mammalian wild-type HSP60. Archives of biochemistry and biophysics 28 26427351
2005 Chaperonin GroEL meets the substrate protein as a "load" of the rings. Journal of biochemistry 28 15944406
2023 Dissecting the Thermodynamics of ATP Binding to GroEL One Nucleotide at a Time. ACS central science 27 36968544
2017 Identifying DCN and HSPD1 as Potential Biomarkers in Colon Cancer Using 2D-LC-MS/MS Combined with iTRAQ Technology. Journal of Cancer 27 28261350
2014 HSP60 is involved in the neuroprotective effects of naloxone. Molecular medicine reports 27 25051048
2019 Hsp60 as a Novel Target in IBD Management: A Prospect. Frontiers in pharmacology 26 30800066
2017 HSP60 activity on human bronchial epithelial cells. International journal of immunopathology and pharmacology 26 28976240
2013 HSP60 as a drug target. Current pharmaceutical design 26 22920899
2011 Identification and immunological characteristics of chaperonin GroEL in Riemerella anatipestifer. Applied microbiology and biotechnology 26 22038245
2010 HSP60, a protein downregulated by IGFBP7 in colorectal carcinoma. Journal of experimental & clinical cancer research : CR 26 20433702
2009 Heat shock protein 60 (HSP60) stimulates neutrophil effector functions. Journal of leukocyte biology 26 19447897
2022 Protein chain collapse modulation and folding stimulation by GroEL-ES. Science advances 24 35245117
2017 miR-382 Contributes to Renal Tubulointerstitial Fibrosis by Downregulating HSPD1. Oxidative medicine and cellular longevity 24 28680529
2009 HSP60 interacts with YB-1 and affects its polysome association and subcellular localization. Biochemical and biophysical research communications 24 19470374
1996 GroEL binds to and unfolds rhodanese posttranslationally. The Journal of biological chemistry 24 8636159
1994 Expression and localization of Trypanosoma cruzi hsp60. Molecular and biochemical parasitology 23 7739666
2016 Lenti-siRNA Hsp60 promote bax in mitochondria and induces apoptosis during heat stress. Biochemical and biophysical research communications 22 27818197
2001 Mechanism of substrate recognition by the chaperonin GroEL. Biochemistry and cell biology = Biochimie et biologie cellulaire 22 11716298
1993 Insulitis-caused redistribution of heat-shock protein HSP60 inside beta-cells correlates with induction of HSP60 autoantibodies. Diabetes 22 8098696
2020 Complex Destabilization in the Mitochondrial Chaperonin Hsp60 Leads to Disease. Frontiers in molecular biosciences 21 32766281
2017 Chaperonin (HSP60) and annexin-2 are candidate biomarkers for non-small cell lung carcinoma. Medicine 21 28178129
2014 Antibodies against Hsp60 and Hsp65 in the sera of women with ovarian cancer. Journal of ovarian research 21 24618330
2007 Chaperonin GroEL: structure and reaction cycle. Current protein & peptide science 21 17979757
2014 HSPD1 interacts with IRF3 to facilitate interferon-beta induction. PloS one 20 25506707

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