Affinage

HSPB1

Heat shock protein beta-1 · UniProt P04792

Length
205 aa
Mass
22.8 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 34 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

HSPB1 (HSP27/HSP25) is an ATP-independent small heat-shock chaperone whose activity is gated by phosphorylation-driven changes in oligomeric state and redox status (PMID:25699602, PMID:30842409, PMID:31845908). Progressive serine phosphorylation at residues 15, 78, and 82 dissociates large oligomers toward chaperone-active dimers, and disulfide reduction further generates highly active monomers in which the dimerization β-strands partially unfold — the dynamic interface to which neuropathy-causing mutations cluster (PMID:25699602, PMID:30842409). Chaperone function toward clients such as tau depends on engagement by the disordered N-terminal region, which is normally sequestered in a binding groove on the α-crystallin domain; release of the NTR activates the chaperone (PMID:31974309). HSPB1 can co-aggregate with unfolded substrates to form smaller, more regular aggregates that are handed off to HSP70 for disaggregation and refolding, independent of its own homo-oligomerization (PMID:34429462). Stress-induced phosphorylation is executed primarily by MK2 downstream of p38 MAPK, and this axis controls HSPB1 solubility, stress-granule dynamics, and stress survival (PMID:16840785, PMID:15687248). Beyond protein quality control, HSPB1 performs distinct client-directed regulatory functions: it inhibits ferroptosis through PKC-mediated phosphorylation that lowers iron-dependent lipid ROS (PMID:25728673); binds GATA-1 in differentiating erythroid cells to drive its ubiquitination and proteasomal degradation (PMID:20410505); binds the autophagy receptor SQSTM1/p62 via the SQSTM1 PB1 domain to support autophagosome formation (PMID:30669930); binds and inhibits PKCδ to suppress cell death (PMID:15731106); promotes MST1 degradation to bias the Hippo pathway toward YAP nuclear localization (PMID:27555231); and stabilizes the actin cytoskeleton via direct, phosphorylation-dependent side-binding to F-actin that protects filaments from stress-induced damage (PMID:12380682, PMID:22007301). In the nervous system, HSPB1 is secreted from astrocytes and taken up by neurons and astrocytes to exert non-cell-autonomous neuroprotection, including reduction of tau pathology, while neuropathy mutations impair anterograde neurofilament transport and autophagy (PMID:23728742, PMID:38507480).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Established that the flexible C-terminal extension contributes to chaperone activity by exposing hydrophobic surface, defining a structural determinant of substrate holding.

    Evidence NMR, CD, analytical ultracentrifugation and thermal aggregation assays on C-terminal deletion mutants of mouse Hsp25

    PMID:10727931

    Open questions at the time
    • Does not resolve how phosphorylation or oligomeric state interacts with C-terminal flexibility
    • Substrate-specific (alpha-lactalbumin vs citrate synthase) differences left unexplained
  2. 2006 High

    Identified MK2 as the major stress-activated kinase phosphorylating Hsp25 at Ser86, linking phosphorylation to oligomer disaggregation, stress-granule formation, and stress survival.

    Evidence MK2-deficient fibroblasts with GFP-Hsp25 imaging, 14-3-3 binding and viability assays under multiple stressors

    PMID:16840785

    Open questions at the time
    • Does not address phosphorylation at other serines (15, 78/82)
    • Downstream client specificity of phosphorylated species not defined
  3. 2015 High

    Mapped how serine phosphorylation tunes oligomeric size, showing that dissociation to dimers is the chaperone-active state — connecting a regulatory modification to a defined functional output.

    Evidence Mass spectrometry of oligomers, phosphomimetic mutagenesis, and amorphous/fibrillar aggregation assays

    PMID:25699602

    Open questions at the time
    • Phosphomimetics approximate but do not equal phosphorylation
    • Relationship between dimer and even smaller species left for later work
  4. 2019 High

    Showed that disulfide reduction yields monomers as the most chaperone-active species and that the dynamic dimer interface harbors neuropathy mutations, tying redox state and disease to structure.

    Evidence Relaxation dispersion and high-pressure NMR with in vitro chaperone assays

    PMID:30842409

    Open questions at the time
    • Monomer prevalence in cells not quantified
    • Causal path from interface dynamics to neuropathy phenotype unestablished
  5. 2020 High

    Resolved that the disordered N-terminal region, sequestered in an ACD groove, is the substrate-engaging element whose release activates chaperone function — distinguishing the functional site from the ACD groove.

    Evidence NMR and mutagenesis with in vitro tau aggregation assays

    PMID:31974309

    Open questions at the time
    • How phosphorylation triggers NTR release in cells not directly shown
    • Generality across non-tau clients not fully tested
  6. 2021 High

    Demonstrated that HSPB1 co-aggregates with substrates to enable HSP70-mediated disaggregation, defining its place in a chaperone relay independent of homo-oligomerization.

    Evidence In vitro reconstitution with purified luciferase/LDH, co-aggregation and disaggregation/refolding assays, oligomerization mutants

    PMID:34429462

    Open questions at the time
    • In-cell relevance of co-aggregate handoff not measured
    • Determinants of HSP70 recruitment to co-aggregates unknown
  7. 2010 High

    Defined a client-directed nuclear function in which phosphorylated HSP27 binds acetylated GATA-1 to drive its proteasomal degradation, controlling terminal erythroid maturation.

    Evidence siRNA knockdown, reciprocal Co-IP, and erythroid differentiation models (K562, CD34+)

    PMID:20410505

    Open questions at the time
    • Ubiquitin ligase responsible for GATA-1 not identified
    • Mechanism of HSP27 nuclear translocation incomplete
  8. 2013 High

    Linked HSPB1 neuropathy mutations to Cdk5 hyperactivation, neurofilament hyperphosphorylation, and impaired kinesin-dependent anterograde transport, providing a disease mechanism.

    Evidence WT/mutant HSPB1 neuronal cells, axonal transport assay, Cdk5 inhibition rescue, NF-kinesin Co-IP

    PMID:23728742

    Open questions at the time
    • How mutant HSPB1 activates Cdk5 not defined
    • Connection to chaperone defect vs gain-of-function unclear
  9. 2013 High

    Established a direct HSPB1–SQSTM1/p62 interaction via the SQSTM1 PB1 domain required for autophagosome formation, extending HSPB1 into autophagy regulation.

    Evidence LC-MS/MS interactome, Co-IP with domain deletion, HSPB1 KO/re-expression rescue

    PMID:30669930

    Open questions at the time
    • Whether chaperone activity is needed for autophagy support not separated
    • Step in phagophore biogenesis affected not pinpointed
  10. 2011 Medium

    Showed HSPB1 binds F-actin directly as a weak side-binder whose interaction dissociates oligomers, and that phosphorylated HSPB1 protects actin filaments from stress damage, connecting oligomeric regulation to cytoskeletal stabilization.

    Evidence Fluorescence binding/EM (Kd ~5.3 µM) and immunofluorescence/fractionation under heat and cytochalasin stress

    PMID:12380682 PMID:22007301

    Open questions at the time
    • Stoichiometry and in-cell binding regime not defined
    • Single-lab biophysical measurements
  11. 2015 High

    Identified HSPB1 as a negative regulator of ferroptosis via PKC-mediated phosphorylation that reduces iron-dependent lipid ROS, placing it in a redox cell-death pathway.

    Evidence siRNA/overexpression, heat-shock pretreatment, xenograft models with erastin

    PMID:25728673

    Open questions at the time
    • Direct lipid/iron targets of phosphorylated HSPB1 not identified
    • How phosphorylation lowers lipid ROS mechanistically unresolved
  12. 2016 Medium

    Extended HSPB1 into Hippo and NADPH pathways: it accelerates MST1 degradation to promote YAP nuclear localization and enhances SIRT2-mediated G6PD deacetylation/activation.

    Evidence siRNA/overexpression epistasis on Hippo components; Co-IP plus G6PD activity and NADPH assays

    PMID:27555231 PMID:27711253

    Open questions at the time
    • Direct vs indirect role in MST1 ubiquitination unresolved
    • Whether HSPB1 stably forms a ternary complex with G6PD-SIRT2 not shown
  13. 2018 High

    Genetically validated the mesenchymal MK2/HSP27 axis as a driver of intestinal tumorigenesis through paracrine effects on epithelial proliferation, apoptosis, and angiogenesis.

    Evidence Conditional cell-type-specific MK2 ablation in Apcmin/+ and colitis-associated carcinogenesis models

    PMID:29844172

    Open questions at the time
    • Specific HSP27 clients producing tumorigenic effectors not identified
    • Phosphorylation-state requirement in vivo not dissected
  14. 2024 Medium

    Demonstrated non-cell-autonomous neuroprotection: astrocyte-secreted HSPB1 is taken up by neurons and astrocytes, dampening inflammation and reducing pathological tau inclusions.

    Evidence Human AD tissue immunostaining, astrocyte secretion/uptake assays, tau inclusion quantification

    PMID:38507480

    Open questions at the time
    • Secretion mechanism not defined
    • Receptor/uptake pathway for extracellular HSPB1 unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many client-specific functions of HSPB1 (ferroptosis, GATA-1 degradation, autophagy, Hippo, actin) are selected and coordinated by a single conformationally/redox-tunable chaperone within cells remains unresolved.
  • No unified model linking oligomeric/phosphorylation state to client choice in cells
  • Most client-directed roles rest on single-lab studies without structural definition of the interaction

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 5 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 2 GO:0140313 molecular sequestering activity 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005576 extracellular region 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2
Partners
G6PDGATA1MST1PRKCDSIRT2SQSTM1VEGFA

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 HSPB1 is a negative regulator of ferroptosis: erastin stimulates HSF1-dependent HSPB1 expression, and protein kinase C (PKC)-mediated HSPB1 phosphorylation protects against ferroptosis by reducing iron-mediated production of lipid reactive oxygen species. Knockdown of HSF1 or HSPB1 enhances erastin-induced ferroptosis, while overexpression inhibits it. siRNA knockdown, overexpression, heat shock pretreatment, xenograft mouse models Oncogene High 25728673
2015 Serine phosphorylation of Hsp27 at residues 15, 78, and 82 (studied via phosphomimetic mutations) progressively reduces oligomeric size, with the triple phosphomimetic mutant existing predominantly as a dimer. Oligomer dissociation enhances chaperone activity against both amorphous and fibrillar aggregation; dimers are the chaperone-active species. Mass spectrometry of oligomeric states, phosphomimetic mutagenesis, chaperone activity assays (amorphous and fibrillar aggregation) Chemistry & biology High 25699602
2019 Reduction of HSP27 oligomers to monomers (by disulfide bond reduction) generates highly chaperone-active monomers; NMR relaxation dispersion and high-pressure NMR show that β-strands mediating dimerization partially unfold in the free monomer, and neuropathy-causing mutations cluster to this dynamic interface region. Relaxation dispersion NMR, high-pressure NMR spectroscopy, in vitro chaperone assay Nature communications High 30842409
2020 HspB1 chaperone activity toward tau requires interactions with its disordered N-terminal region (NTR), not the ACD binding groove alone. The NTR is held in a binding groove on the ACD, and mutations disrupting these intrinsic ACD-NTR interactions greatly enhance chaperone activity. ACD groove binding is uncorrelated with chaperone function. NMR spectroscopy, mutagenesis, in vitro chaperone aggregation assay with tau Proceedings of the National Academy of Sciences of the United States of America High 31974309
2020 A spherical 24-monomer Hsp27 complex (12 dimers) contains a phosphorylation pocket flanked by serine residues between N-terminal domains. Ivermectin directly binds this pocket to inhibit MAPKAP2 (MK2)-mediated Hsp27 phosphorylation and depolymerization, blocking HSP27-regulated survival signaling and client-oncoprotein interactions. Biochemical, structural, and computational experiments; direct binding assay; kinase inhibition assay; tumor models The Journal of clinical investigation High 31845908
2021 Human HSPB1 co-aggregates with unfolded protein substrates (luciferase, lactate dehydrogenase), forming smaller and more regularly shaped aggregates. Co-aggregated HSPB1 facilitates downstream disaggregation and refolding by HSP70; HSPB1 homo-oligomerization is not required for this activity. In vitro reconstitution with purified proteins, co-aggregation assay, disaggregation/refolding assay, oligomerization mutants Scientific reports High 34429462
2010 In late-stage erythroid differentiation, HSP27 is phosphorylated in a p38-dependent manner, translocates to the nucleus, binds to GATA-1, and induces GATA-1 ubiquitination and proteasomal degradation, provided that GATA-1 is acetylated. HSP27 depletion causes GATA-1 accumulation and impairs terminal erythroid maturation. siRNA knockdown, co-immunoprecipitation, Western blot, erythroid differentiation models (K562, CD34+ cells), phosphorylation analysis Blood High 20410505
2000 The C-terminal extension of mouse Hsp25 is required for full chaperone activity; deletion reduces accessible hydrophobic surface, and the C-terminal extension remains flexible during interaction with unfolded substrate (dithiothreitol-reduced alpha-lactalbumin). The mutant lacking this extension cannot stabilize alpha-lactalbumin against precipitation but retains comparable activity against citrate synthase thermal aggregation. 1H NMR spectroscopy, CD spectroscopy, analytical ultracentrifugation, electron microscopy, chaperone thermal aggregation assay, C-terminal deletion mutagenesis European journal of biochemistry High 10727931
2019 HSPB1 binds the autophagy receptor SQSTM1/p62 via the PB1 domain of SQSTM1. HSPB1 knockout impairs autophagosome formation, and neuropathy-causing HSPB1 mutations reduce formation of SQSTM1/p62 bodies and impair phagophore formation, suggesting HSPB1 regulates autophagy via SQSTM1 interaction. LC-MS/MS interactome analysis, co-immunoprecipitation, HSPB1 knockout cells, re-expression rescue, patient-derived motor neurons Autophagy High 30669930
2005 HSP25 binds directly to kinase-active PKCdelta and inhibits its kinase activity and membrane translocation, reducing cell death. The binding site maps to amino acids 90–103 of HSP25 and the C-terminal V5 region of PKCdelta. This interaction induces HSP25 phosphorylation at Ser-15 and Ser-86, which promotes HSP25 release from PKCdelta. Co-immunoprecipitation, deletion construct mapping, in vitro kinase assay, cell death assay, phosphorylation analysis The Journal of biological chemistry High 15731106
2016 Hsp27 regulates the Hippo tumor suppressor pathway by accelerating proteasomal degradation of ubiquitinated MST1 (the core Hippo kinase), resulting in reduced phosphorylation/activity of LATS1 and MOB1, leading to YAP nuclear localization. Hsp27 knockdown induces YAP phosphorylation and cytoplasmic retention. siRNA knockdown, overexpression, functional genomics, Western blot for pathway components, cancer cell lines (prostate, breast, lung) Scientific reports Medium 27555231
2013 Neuropathy-causing HSPB1 mutations increase Cdk5-mediated phosphorylation of neurofilaments (NFs), reduce NF binding to the anterograde motor kinesin, and impair anterograde NF transport. Inhibition of Cdk5/p35 restores NF phosphorylation levels and NF-kinesin binding in mutant HSPB1 neuronal cells. Stable transduction of neuronal cells with WT/mutant HSPB1, axonal transport assay, Cdk5 inhibition, co-immunoprecipitation of NF-kinesin Acta neuropathologica High 23728742
2016 HSPB1 activates G6PD by enhancing the binding between G6PD and SIRT2, leading to SIRT2-mediated deacetylation and activation of G6PD, thereby sustaining cellular NADPH and pentose production in response to oxidative stress. Co-immunoprecipitation, overexpression/knockdown, G6PD activity assay, NADPH measurement PloS one Medium 27711253
2000 HSP25 is required for cardiomyocyte differentiation of P19 cells; antisense HSP25 expression reduces cardiac actin and desmin expression and cardiac mRNA levels. The p38/SAPK2 pathway is required only during the first 2 days of differentiation (before HSP25 induction), acting on Brachyury-T expression, while HSP25 itself acts later. Phosphorylation of HSP25 by p38 is not required for its function in cardiomyocyte differentiation. Antisense expression, pharmacological inhibition (SB203580, PD90589), P19 cell differentiation model Developmental biology Medium 10656759
2006 MK2 (MAPKAP kinase 2) is the major kinase responsible for stress-induced Hsp25 phosphorylation at Ser86. In MK2-deficient cells, no stress-dependent Hsp25 phosphorylation occurs, disaggregation of Hsp25 complexes is impaired, and stress-induced insolubilization/stress granule formation is delayed. MK2-dependent insolubilization correlates with increased susceptibility to arsenite, H2O2, and sublethal heat shock. MK2-deficient fibroblasts (genetic model), GFP-Hsp25 imaging, in vitro 14-3-3 binding assay, cell viability/apoptosis assay The Journal of biological chemistry High 16840785
2011 Phosphorylated Hsp25 directly associates with actin microfilament bundles after mild heat stress (in a p38/phosphorylation-dependent manner), and this association protects actin filaments from cytochalasin-induced damage or severe heat stress. Nuclear Hsp25-containing granules can bind heat-denatured nucleosolic proteins (demonstrated by colocalization with denatured luciferase). Immunofluorescence, drug treatments (cantharidin, SB203580), Triton X-100 fractionation, isoform analysis, transfected luciferase colocalization Cell stress & chaperones Medium 12380682
2011 Hsp27 directly interacts with F-actin as a weak side-binding protein (not an end-capper) with Kd ~5.3 μM; interaction dissociates Hsp27 oligomers to monomers as assessed by pyrene excimer fluorescence loss. Hsp27 is not a strong G-actin sequester. Fluorescence binding assay (acrylodan and pyrene probes), EM imaging, titration experiments Biochemistry research international Medium 22007301
2011 BMP-2 activates the p38/MK2/Hsp25 signaling pathway in mesenchymal cells, downstream of BMP receptors. Phosphorylated Hsp25 colocalizes with BMP receptor complexes in lamellipodia, and overexpression of a phosphorylation-mutant Hsp25 abolishes BMP-2-induced cell migration, indicating Hsp25 phosphorylation is required for BMP-2-induced actin remodeling and migration. Chemical inhibition (p38 inhibitor), genetic ablation of p38α and MK2, overexpression of phosphorylation mutant Hsp25, immunofluorescence colocalization, migration assay PloS one High 21297993
2018 Mesenchymal MAPKAPK2 (MK2) is required for Hsp27 phosphorylation in intestinal mesenchymal cells, and this MK2/Hsp27 axis drives downstream production of tumorigenic effector molecules affecting epithelial proliferation, apoptosis, and angiogenesis. MK2 deletion in intestinal mesenchymal cells reduces tumor multiplicity and growth. Complete and conditional MK2 genetic ablation (Apcmin/+ model and colitis-associated carcinogenesis), Western blot for Hsp27 phosphorylation Proceedings of the National Academy of Sciences of the United States of America High 29844172
2014 MMP9 cleaves HSPB1 at defined sites, releasing C-terminal HSPB1 fragments that inhibit VEGF-induced endothelial cell activation and have greater VEGF-binding affinity than full-length HSPB1. MMP9-mediated HSPB1 cleavage occurs in vivo during tumor progression, and the C-terminal fragment reduces tumor progression. In vitro cleavage mapping, co-immunoprecipitation with VEGF, MMP9 null mice, in vivo tumor models (B16F10, CT26) PloS one Medium 24465581
2013 Wild-type HSPB1 directly interacts with SQSTM1/p62 via co-immunoprecipitation, and the PB1 domain of SQSTM1 is essential for this interaction. In HSPB1 knockout cells, autophagosome formation is impaired and rescued by HSPB1 re-expression. Co-immunoprecipitation, LC-MS/MS, HSPB1 KO cells, re-expression rescue, domain deletion mutants Autophagy High 30669930
2000 Hsp25 overexpression increases cellular resistance to ionizing radiation and reduces radiation-induced apoptosis by augmenting the glutathione-redox cycle — specifically by increasing glutathione reductase and glutathione peroxidase activities and increasing the GSH/GSSG ratio, rather than by increasing de novo GSH synthesis. Stable transfection overexpression, radiation survival assay, apoptosis measurement, enzyme activity assays (glutathione reductase, glutathione peroxidase, gamma-GCS), GSH/GSSG quantification Journal of cellular physiology Medium 10699971
2018 P2RX7 signaling suppresses HSPB1 expression through MAPK1/2-mediated SP1 phosphorylation. Absence of P2rx7 leads to prolonged HSPB1 induction, which triggers ER stress and PRKAA1/ULK1- and AKT1/GSK3B/SH3GLB1-mediated autophagic pathways (independent of mTOR) in astrocytes. P2RX7 knockout, HSPB1 overexpression/knockdown, Western blot for signaling components, ER stress markers, autophagy markers in astroglial cells Cell death & disease Medium 29749377
2009 Hsp27 overexpression in renal epithelial cells preserves cell-cell junction function (E-cadherin distribution, transepithelial resistance) and cell-substrate interactions (paxillin at focal adhesions) during metabolic stress. Hsp27 overexpression reduces active c-Src accumulation at cell contact sites, while Hsp27 did not co-immunoprecipitate with c-Src and did not inhibit whole-cell c-Src activation. Overexpression, siRNA knockdown, transepithelial electrical resistance, co-immunoprecipitation (negative for direct binding), immunofluorescence, cell fractionation American journal of physiology. Renal physiology Medium 19553351
2024 HSPB1 is secreted from astrocytes (demonstrated in human AD brain tissue and in vitro under inflammatory conditions). Astrocyte-secreted HSPB1 is taken up by both astrocytes and neurons, attenuating inflammatory responses in reactive astrocytes and reducing pathological tau inclusions in neurons. Human AD brain immunostaining, astrocyte secretion assays, uptake assays in astrocytes and neurons, tau inclusion quantification Science advances Medium 38507480
2024 crVDAC3 (a circular RNA from VDAC3) directly binds HSPB1 protein and inhibits its ubiquitination and degradation, leading to HSPB1 accumulation. Suppression of crVDAC3 reduces HSPB1 levels and induces ferroptosis in breast cancer cells via increased ROS and labile iron pool. RNA pull-down, mass spectrometry, RNA immunoprecipitation, co-immunoprecipitation, ferroptosis markers, shRNA library screening Drug resistance updates Medium 39243601
2021 HSPB1 undergoes S-thiolated (homooxidized) modification and Bmal1 regulates the redox oscillation of HSPB1. The HSPB1-C141S mutant (unable to form homooxidized form) accelerates cardiomyocyte apoptosis, increases ROS, and decreases GSH during oxidative stress. Knockdown of Bmal1 decreases homooxidized HSPB1, while overexpression increases it. C141S mutagenesis, Bmal1 knockdown/overexpression, ROS measurement, GSH quantification, apoptosis assay in H9c2 cells and neonatal rat cardiomyocytes Oxidative medicine and cellular longevity Medium 34239687
2023 FYN directly phosphorylates TOPK at Y272, and activated TOPK in turn phosphorylates HSPB1 at Ser15. TOPK knockout mice show decreased HSPB1 and p-HSPB1(Ser15), placing HSPB1 downstream of the FYN-TOPK axis in gastric cancer progression. Co-immunoprecipitation, pull-down assay, in vitro kinase assay, 32P-labeled isotope radioautography, phosphoproteomics, TOPK knockout mice, immunofluorescence co-localization Journal of experimental & clinical cancer research Medium 37016377
2013 In embryonic zebrafish, reduction of HspB1 expression decreases myofiber cross-sectional area by up to 47% in craniofacial muscles without affecting myofibril number, nuclei, chondrocytes, sarcomere organization, or myofibril development, indicating a specific role for HspB1 in myofibril growth. Morpholino knockdown in zebrafish, quantitative morphometric analysis of myofibers Experimental cell research Medium 23313812
2005 p38 MAPK/HSP25 signaling mediates cadmium-induced contraction of mesangial cells and glomeruli. Cadmium activates p38, leading to sequential phosphorylation of HSP25 at Ser15 then Ser86, reduction of HSP25 oligomeric size, and HSP25 association with microfilaments. This process is blocked by the p38 inhibitor SB-203580 and by a dominant-negative p38 mutant. p38 dominant-negative expression, SB-203580 treatment, HSP25 phosphorylation/oligomerization analysis, microfilament co-fractionation, isolated glomeruli contraction assay American journal of physiology. Renal physiology Medium 15687248
2008 Flagellin activates TLR5 on the basolateral surface of intestinal epithelial cells, stimulating p38 MAPK, which in turn induces Hsp25 expression transcriptionally. siRNA knockdown of Hsp25 partially abrogates flagellin-mediated protection against oxidant stress, establishing Hsp25 as a downstream effector of TLR5/p38 signaling in intestinal epithelial cytoprotection. siRNA knockdown, luciferase reporter assay, actinomycin D treatment, p38 inhibition, polarized cell model, mouse Salmonella infection model American journal of physiology. Gastrointestinal and liver physiology Medium 18202113
2003 HSP25 is involved in two steps of keratinocyte differentiation: early transient hyperphosphorylation is essential for expression of differentiation markers, and later, the chaperone-active unphosphorylated form is organized into aggregates involved in keratin filament network dynamics. Quantitative immunoassay, phosphorylation analysis, temporal analysis during PAM212 keratinocyte differentiation in vitro The Journal of biological chemistry Medium 14662766
2014 HspB1 co-expression in cells expressing AβPP increases cellular holoAβPP and C-terminal fragments and attenuates Aβ42 release from AβPPsw cells, indicating HspB1 modulates APP processing. HspB1 was shown to interact with Aβ or its precursor AβPP in this cellular context. Stable cell line co-expression, Western blot for APP fragments, ELISA for Aβ40/42, co-immunoprecipitation Journal of Alzheimer's disease Low 24898650
2017 Astrocyte-specific overexpression of wild-type HSPB1 attenuates SOD1(G93A) astrocyte-mediated toxicity in motor neurons in a co-culture model, whereas mutant HSPB1 fails to protect. Expression of a phosphomimetic HSPB1 mutant in SOD1(G93A) astrocytes also reduces motor neuron toxicity, suggesting phosphorylation contributes to HSPB1-mediated neuroprotection. Astrocyte-motor neuron co-culture model, wild-type vs. mutant HSPB1 overexpression, phosphomimetic mutant, motor neuron viability assay Experimental neurology Medium 28797631

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene 552 25728673
1993 Biological and clinical implications of heat shock protein 27,000 (Hsp27): a review. Journal of the National Cancer Institute 491 8411230
2003 On the role of Hsp27 in regulating apoptosis. Apoptosis : an international journal on programmed cell death 437 12510153
2007 Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targets. FEBS letters 258 17467701
2012 Small heat shock proteins HSP27 (HspB1), αB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death. The international journal of biochemistry & cell biology 231 22521623
2012 Heat shock protein 27 (HSP27): biomarker of disease and therapeutic target. Fibrogenesis & tissue repair 223 22564335
2008 Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2. Neurology 158 18832141
1993 Alpha B crystallin and HSP28 are enhanced in the cerebral cortex of patients with Alzheimer's disease. Journal of the neurological sciences 145 8277336
2020 Apoptosis, autophagy and atherosclerosis: Relationships and the role of Hsp27. Pharmacological research 119 33053445
2009 HSP27: mechanisms of cellular protection against neuronal injury. Current molecular medicine 110 19860665
2000 Mouse Hsp25, a small shock protein. The role of its C-terminal extension in oligomerization and chaperone action. European journal of biochemistry 107 10727931
2015 Phosphomimics destabilize Hsp27 oligomeric assemblies and enhance chaperone activity. Chemistry & biology 106 25699602
2000 Hsp25 and the p38 MAPK pathway are involved in differentiation of cardiomyocytes. Developmental biology 96 10656759
2019 Local unfolding of the HSP27 monomer regulates chaperone activity. Nature communications 87 30842409
2017 Mammalian HspB1 (Hsp27) is a molecular sensor linked to the physiology and environment of the cell. Cell stress & chaperones 84 28144778
2000 Role of small heat shock protein HSP25 in radioresistance and glutathione-redox cycle. Journal of cellular physiology 84 10699971
2024 crVDAC3 alleviates ferroptosis by impeding HSPB1 ubiquitination and confers trastuzumab deruxtecan resistance in HER2-low breast cancer. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 81 39243601
1992 Growth arrest of human B lymphocytes is accompanied by induction of the low molecular weight mammalian heat shock protein (Hsp28). Journal of immunology (Baltimore, Md. : 1950) 79 1541812
2004 Surface expression of Hsp25 and Hsp72 differentially regulates tumor growth and metastasis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 72 15627887
2005 HSP27 and cell survival in neurones. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 65 16048837
2012 Targeting heat shock protein 27 (HspB1) interferes with bone metastasis and tumour formation in vivo. British journal of cancer 64 22627320
2019 Neuropathy-causing mutations in HSPB1 impair autophagy by disturbing the formation of SQSTM1/p62 bodies. Autophagy 62 30669930
2010 HSP27 controls GATA-1 protein level during erythroid cell differentiation. Blood 62 20410505
2004 Schisandrin B protects myocardial ischemia-reperfusion injury partly by inducing Hsp25 and Hsp70 expression in rats. Molecular and cellular biochemistry 61 15646035
2020 Ivermectin inhibits HSP27 and potentiates efficacy of oncogene targeting in tumor models. The Journal of clinical investigation 58 31845908
2011 HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II. Laboratory investigation; a journal of technical methods and pathology 56 21931298
2002 Regulation and localization of HSP70 and HSP25 in the kidney of rats undergoing long-term administration of angiotensin II. Hypertension (Dallas, Tex. : 1979) 56 11799090
2002 Distribution, phosphorylation, and activities of Hsp25 in heat-stressed H9c2 myoblasts: a functional link to cytoprotection. Cell stress & chaperones 56 12380682
2010 HspB1 (Hsp 27) expression and neuroprotection in the retina. Molecular neurobiology 51 20514530
2016 Molecular chaperone Hsp27 regulates the Hippo tumor suppressor pathway in cancer. Scientific reports 48 27555231
2018 P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy. Cell death & disease 47 29749377
2009 The small heat shock protein HSP25 protects astrocytes against stress induced by proteasomal inhibition. Glia 47 19330846
2014 Hsp27 as a therapeutic target in cancers. Current drug targets 46 24138636
2020 Release of a disordered domain enhances HspB1 chaperone activity toward tau. Proceedings of the National Academy of Sciences of the United States of America 45 31974309
2013 Charcot-Marie-Tooth causing HSPB1 mutations increase Cdk5-mediated phosphorylation of neurofilaments. Acta neuropathologica 45 23728742
2013 Overexpression of a Metarhizium robertsii HSP25 gene increases thermotolerance and survival in soil. Applied microbiology and biotechnology 45 24265026
2010 HSPB1, actin filament dynamics, and aging cells. Annals of the New York Academy of Sciences 45 20536836
2005 HSP25 inhibits protein kinase C delta-mediated cell death through direct interaction. The Journal of biological chemistry 45 15731106
2016 A Targetable Molecular Chaperone Hsp27 Confers Aggressiveness in Hepatocellular Carcinoma. Theranostics 44 26941848
2016 HSPB1 Enhances SIRT2-Mediated G6PD Activation and Promotes Glioma Cell Proliferation. PloS one 44 27711253
2007 Hsp27 phosphorylation in experimental glaucoma. Investigative ophthalmology & visual science 44 17724197
2013 HSP27 is required for invasion and metastasis triggered by hepatocyte growth factor. International journal of cancer 41 23996744
2005 Silencing the hsp25 gene eliminates migration capability of the highly metastatic murine 4T1 breast adenocarcinoma cell. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 16340246
2022 The Role of Hsp27 in Chemotherapy Resistance. Biomedicines 39 35453647
2005 p38 MAPK/HSP25 signaling mediates cadmium-induced contraction of mesangial cells and renal glomeruli. American journal of physiology. Renal physiology 39 15687248
2003 Hsp25 and Hsp70 in rodent tumors treated with doxorubicin and lovastatin. Cell stress & chaperones 39 12820652
2003 HSP25 is involved in two steps of the differentiation of PAM212 keratinocytes. The Journal of biological chemistry 38 14662766
2011 The expression and clinical significance of CLIC1 and HSP27 in lung adenocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 21858536
1991 Mammalian stress proteins HSP70 and HSP28 coinduced by nicotine and either ethanol or heat. Molecular and cellular biology 37 1944275
2018 Mesenchymal MAPKAPK2/HSP27 drives intestinal carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 36 29844172
2011 The p38/MK2/Hsp25 pathway is required for BMP-2-induced cell migration. PloS one 36 21297993
2008 HSP27: an anti-inflammatory and immunomodulatory stress protein acting to dampen immune function. Novartis Foundation symposium 36 18575275
2006 Analysis of properties of small heat shock protein Hsp25 in MAPK-activated protein kinase 2 (MK2)-deficient cells: MK2-dependent insolubilization of Hsp25 oligomers correlates with susceptibility to stress. The Journal of biological chemistry 36 16840785
2013 Peptide aptamers: tools to negatively or positively modulate HSPB1(27) function. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 35 23530261
1993 Responses to heat shock of alpha B crystallin and HSP28 in U373 MG human glioma cells. Biochimica et biophysica acta 35 8435441
2015 Overexpression of mutant HSP27 causes axonal neuropathy in mice. Journal of biomedical science 34 26141737
2012 Role of human and mouse HspB1 in metastasis. Current molecular medicine 34 22804237
2014 Heat-shock protein 27 (HSP27, HSPB1) is up-regulated by MET kinase inhibitors and confers resistance to MET-targeted therapy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 24903273
2012 Association between DNA methylation of HSPB1 and death in low Gleason score prostate cancer. Prostate cancer and prostatic diseases 32 23165430
1997 Effect of protein kinase inhibitors on activity of mammalian small heat-shock protein (HSP25) kinase. Biochemical pharmacology 32 9214684
2024 Reactive astrocytes secrete the chaperone HSPB1 to mediate neuroprotection. Science advances 31 38507480
2001 Hsp25 and -90 immunoreactivity in the normal rat eye. Investigative ophthalmology & visual science 31 11687552
1997 Heat-shock protein 27 (HSP27) and its role in female reproductive organs. European journal of gynaecological oncology 31 9061315
2002 Expression pattern of HSP25 in mouse preimplantation embryo: heat shock responses during oocyte maturation. Molecular reproduction and development 30 11774370
2017 Upregulation and phosphorylation of HspB1/Hsp25 and HspB5/αB-crystallin after transient middle cerebral artery occlusion in rats. Cell stress & chaperones 27 28425051
2016 Melatonin reverses morphine tolerance by inhibiting microglia activation and HSP27 expression. Life sciences 27 27012766
2015 Truncated HSPB1 causes axonal neuropathy and impairs tolerance to unfolded protein stress. BBA clinical 27 26675522
2021 The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70. Scientific reports 26 34429462
2011 Structure-functions of HspB1 (Hsp27). Methods in molecular biology (Clifton, N.J.) 26 21898231
2024 Ginsenoside Rg5 inhibits glioblastoma by activating ferroptosis via NR3C1/HSPB1/NCOA4. Phytomedicine : international journal of phytotherapy and phytopharmacology 25 38640858
2016 Advances in HSP27 and HSP90-targeting strategies for glioblastoma. Journal of neuro-oncology 24 26842818
2016 Novel HSPB1 mutation causes both motor neuronopathy and distal myopathy. Neurology. Genetics 24 27830184
2013 Synthesis and anticancer mechanism investigation of dual Hsp27 and tubulin inhibitors. Journal of medicinal chemistry 24 23767669
2021 Bmal1 Regulates the Redox Rhythm of HSPB1, and Homooxidized HSPB1 Attenuates the Oxidative Stress Injury of Cardiomyocytes. Oxidative medicine and cellular longevity 23 34239687
2016 The Clinical Significance of Phosphorylated Heat Shock Protein 27 (HSPB1) in Pancreatic Cancer. International journal of molecular sciences 23 26805817
2016 Overcoming HSP27-mediated resistance by altered dimerization of HSP27 using small molecules. Oncotarget 23 27449291
1992 Development of acute thermotolerance in L929 cells: lack of HSP28 synthesis and phosphorylation. Journal of cellular physiology 23 1618914
2005 Regulation of HSP25 expression and phosphorylation in functionally overloaded rat plantaris and soleus muscles. Journal of applied physiology (Bethesda, Md. : 1985) 22 16223977
2023 FYN/TOPK/HSPB1 axis facilitates the proliferation and metastasis of gastric cancer. Journal of experimental & clinical cancer research : CR 21 37016377
2016 Expression of HSP27 in Hepatocellular Carcinoma. Anticancer research 21 27354654
2014 MMP9 processing of HSPB1 regulates tumor progression. PloS one 21 24465581
2019 The effects of HSP27 against UVB-induced photoaging in rat skin. Biochemical and biophysical research communications 20 30902393
2017 HSPB1 mutations causing hereditary neuropathy in humans disrupt non-cell autonomous protection of motor neurons. Experimental neurology 20 28797631
2014 αB-crystallin and HSP27 in glial cells in tauopathies. Neuropathology : official journal of the Japanese Society of Neuropathology 20 24985029
2020 Mutations in HspB1 and hereditary neuropathies. Cell stress & chaperones 19 32301006
2011 Hsp27-actin interaction. Biochemistry research international 19 22007301
2004 Differential inhibition of HSP72 and HSP25 produces profound impairment of cellular integrity. Journal of the American Society of Nephrology : JASN 19 15153566
1991 Differences in preferential synthesis and redistribution of HSP70 and HSP28 families by heat or sodium arsenite in Chinese hamster ovary cells. Journal of cellular physiology 19 1939348
2021 HSP27 protects against ferroptosis of glioblastoma cells. Human cell 18 34791597
2017 Sustained HSP25 Expression Induces Clasmatodendrosis via ER Stress in the Rat Hippocampus. Frontiers in cellular neuroscience 18 28275338
2013 3,4-DGE is cytotoxic and decreases HSP27/HSPB1 in podocytes. Archives of toxicology 18 24337777
2018 HSP27 inhibitor attenuates radiation-induced pulmonary inflammation. Scientific reports 17 29520071
2014 Modulation of amyloid-β protein precursor expression by HspB1. Journal of Alzheimer's disease : JAD 17 24898650
2023 The miR-15b-Smurf2-HSP27 axis promotes pulmonary fibrosis. Journal of biomedical science 16 36611161
2022 HSPB1 Regulates Autophagy and Apoptosis in Vascular Smooth Muscle Cells in Arteriosclerosis Obliterans. Cardiovascular therapeutics 16 36474716
2019 Melanoma migration is promoted by prion protein via Akt-hsp27 signaling axis. Biochemical and biophysical research communications 16 31870551
2016 HSPB1 deficiency sensitizes melanoma cells to hyperthermia induced cell death. Oncotarget 16 27626679
2013 Small heat shock protein HSPB1 regulates growth of embryonic zebrafish craniofacial muscles. Experimental cell research 16 23313812
2009 Hsp27 inhibits sublethal, Src-mediated renal epithelial cell injury. American journal of physiology. Renal physiology 16 19553351
2008 Flagellin is required for salmonella-induced expression of heat shock protein Hsp25 in intestinal epithelium. American journal of physiology. Gastrointestinal and liver physiology 16 18202113

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