Affinage

HMGB1

High mobility group protein B1 · UniProt P09429

Length
215 aa
Mass
24.9 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 24 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

HMGB1 is a multifunctional protein that bridges nuclear chromatin architecture, DNA repair, and extracellular danger signaling, with its activity in each compartment governed by domain structure and post-translational/redox state (PMID:1425584, PMID:20819940, PMID:23207101). In the nucleus it functions as an architectural DNA-binding protein: its tandem HMG-box domains recognize distorted and structured DNA (four-way junctions, cisplatin adducts) in a sequence-independent manner, bend and unwind the duplex, and can loop, compact, and supercoil DNA, while the acidic C-terminal tail folds back onto the boxes to tune their specificity for structured over linear DNA (PMID:1425584, PMID:226939, PMID:8152909, PMID:10212205, PMID:17585880). Through these activities HMGB1 stimulates p53 DNA binding and transactivation by promoting higher-order nucleoprotein assembly (PMID:9472015), promotes DNA end joining by juxtaposing DNA ends (PMID:10866811), and acts as a cofactor in base excision repair, directing repair toward the long-patch sub-pathway (PMID:20123074). In the cytoplasm HMGB1 promotes autophagy by binding Beclin1 and displacing Bcl-2 in a manner requiring the C23–C45 disulfide bond, an activity reciprocally restrained by complex formation with p53 (PMID:20819940, PMID:22345153). HMGB1 release is actively controlled: PARP-1 drives PARylation and an increased HAT/HDAC ratio to acetylate HMGB1 and trigger nuclear-to-cytoplasmic translocation (PMID:25392528), AMPK phosphorylates HMGB1 during cuproptosis (PMID:36211458), and autophagy-dependent HDAC inhibition promotes its acetylation and release during ferroptosis (PMID:30686534), with PKR-dependent inflammasome activity required for secretion but pyroptotic membrane rupture governing actual release in macrophages (PMID:22801494, PMID:32917873). Once extracellular, HMGB1's function is redox-determined: the all-thiol form pairs with CXCL12 to chemoattract leukocytes via CXCR4, the C23–C45 disulfide form activates TLR4 to induce cytokines, and full oxidation abolishes activity (PMID:23373897, PMID:23207101); it additionally signals through TLR5 via its C-terminal tail to drive MyD88/NF-κB-dependent inflammation and pain (PMID:27760316), and through RAGE to mediate endocytosis, M2 macrophage polarization with C1q, and inflammation from regulated cell death (PMID:30686534, PMID:36211458, PMID:27683415, PMID:29530410). Nociceptor-derived HMGB1 is required for neurogenic inflammation in vivo (PMID:34385304).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1979 High

    Established that HMGB1 actively alters DNA topology rather than passively coating DNA, defining a biochemical basis for its architectural role.

    Evidence DNA melting and competition unwinding assays measuring unwinding angle and thermal stability in vitro

    PMID:226939

    Open questions at the time
    • Did not define structural preference for distorted DNA
    • No domain-level dissection of the unwinding activity
  2. 1992 High

    Showed HMGB1's HMG-box recognizes DNA by structure rather than sequence and bends the duplex, explaining how it targets junctions and distorted sites.

    Evidence In vitro four-way junction and linear duplex binding, gel shift and footprinting

    PMID:1425584

    Open questions at the time
    • Role of the acidic tail not addressed
    • Cellular consequences of structure-specific binding untested
  3. 1994 High

    Defined the acidic C-terminal tail as an autoregulatory element that downregulates and tunes the DNA-binding/supercoiling activity of the tandem boxes.

    Evidence Supercoiling assays, EM, and comparison of full-length vs tail-deleted HMG3

    PMID:8152909

    Open questions at the time
    • Molecular mechanism of tail-box interaction not yet structurally resolved
    • Physiological setting of looping/compaction unclear
  4. 1994 Medium

    Characterized the gene structure and TATA-less CpG-island promoter, supporting ubiquitous expression with no encoded membrane-targeting signal.

    Evidence Gene isolation, exon mapping, reporter assays in mouse hmg1

    PMID:7961836

    Open questions at the time
    • Regulation of expression in stress/inflammation not addressed
    • Secretion route left unexplained given lack of signal sequence
  5. 1998 High

    Linked HMGB1's DNA architecture to transcription by showing it directly binds p53 and stimulates its DNA binding and transactivation.

    Evidence Biochemical purification, recombinant in vitro binding, transactivation assays

    PMID:9472015

    Open questions at the time
    • Genomic targets of HMGB1/p53 cooperation not mapped
    • In vivo relevance to p53 programs untested here
  6. 1999 High

    Quantified high-affinity binding and severe bending of cisplatin-damaged DNA, mechanistically connecting HMGB1 to recognition of damaged DNA.

    Evidence FRET distance measurement and stopped-flow kinetics with HMG1 domain B

    PMID:10212205

    Open questions at the time
    • Downstream effect on repair or cisplatin sensitivity not assessed
    • Only domain B examined
  7. 2000 High

    Showed HMGB1 physically juxtaposes DNA ends to stimulate ligation, mapping the activity to the B domain and flanking basic residues.

    Evidence In vitro T4 ligase joining assays, EM/SFM, domain mutagenesis

    PMID:10866811

    Open questions at the time
    • Relevance to cellular NHEJ pathway not established
    • Partner repair factors not identified
  8. 2010 Medium

    Defined HMGB1 as a base excision repair cofactor that biases repair toward the long-patch sub-pathway, with potential consequences for repeat instability.

    Evidence In vitro reconstituted BER assays and cross-linking to BER intermediates

    PMID:20123074

    Open questions at the time
    • Single lab, in vitro reconstitution
    • BER enzyme contacts not structurally defined
    • In vivo repair phenotype not shown
  9. 2010 High

    Established the cytoplasmic autophagy function of HMGB1, showing it binds Beclin1, displaces Bcl-2, and requires the C23–C45 disulfide bond, with ROS driving cytosolic translocation.

    Evidence Reciprocal Co-IP, cysteine mutagenesis, autophagy flux in KO/KD cells

    PMID:20819940

    Open questions at the time
    • Structural basis of Beclin1 binding not resolved
    • Redox sensing mechanism of translocation unclear
  10. 2011 Medium

    Revealed an intracellular brake on efferocytosis by showing HMGB1 inhibits Src-FAK interaction and dampens Rac1-driven phagocytic cytoskeletal signaling.

    Evidence siRNA knockdown phenotypes plus in vitro pulldown of purified FAK/Src with HMGB1

    PMID:21957148

    Open questions at the time
    • Single lab
    • Binding site on Src not mapped
    • In vivo efferocytosis relevance untested
  11. 2012 High

    Placed PKR upstream of inflammasome-dependent HMGB1 secretion, reconstituting inflammasome activity in a cell-free system.

    Evidence PKR KO/inhibition, Co-IP with inflammasome components, cell-free reconstitution, in vivo peritonitis

    PMID:22801494

    Open questions at the time
    • Direct PKR substrates within the inflammasome not defined
    • Link to membrane permeabilization not addressed
  12. 2012 High

    Demonstrated that HMGB1's chemoattractant activity is mediated by an all-thiol HMGB1–CXCL12 heterocomplex acting on CXCR4, distinct from its disulfide-dependent TLR4 cytokine activity.

    Evidence Complex characterization, CXCR4 binding and leukocyte migration with defined redox isoforms

    PMID:23207101

    Open questions at the time
    • Structure of the HMGB1–CXCL12 complex not resolved
    • In vivo redox dynamics not quantified
  13. 2012 Medium

    Showed the HMGB1–p53 complex reciprocally regulates autophagy and apoptosis by controlling each partner's cytoplasmic localization, with p53 restraining the HMGB1/Beclin1 axis.

    Evidence Reciprocal Co-IP and p53/HMGB1 KO with subcellular fractionation and autophagy readout

    PMID:22345153

    Open questions at the time
    • Single lab
    • Direct competition with Beclin1 not biochemically isolated
  14. 2013 Medium

    Refined the redox code by showing the C23–C45 disulfide plus reduced C106 confers TLR4/cytokine activity while C106 oxidation enforces tolerance, separating chemoattractant and cytokine functions.

    Evidence Defined recombinant redox isoforms in TLR4 activation and leukocyte recruitment assays

    PMID:23373897

    Open questions at the time
    • Per-experiment evidence from single lab
    • In vivo redox transition kinetics not measured
  15. 2016 Medium

    Identified TLR5 as an HMGB1 receptor driving MyD88/NF-κB inflammation and pain, mapping the interaction to the C-terminal tail.

    Evidence Biophysical binding, NF-κB assays in TLR5 cells, in vivo allodynia, C-terminal truncation

    PMID:27760316

    Open questions at the time
    • Single lab
    • Redox-state dependence of TLR5 binding not tested
  16. 2016 Medium

    Showed HMGB1 can drive anti-inflammatory M2 polarization when cooperating with C1q via RAGE and LAIR-1, balancing its pro-inflammatory M1 activity.

    Evidence Monocyte differentiation with C1q/HMGB1 co-stimulation and RAGE/LAIR-1 blocking

    PMID:27683415

    Open questions at the time
    • Single lab
    • Molecular composition of the C1q/HMGB1/RAGE/LAIR-1 complex not resolved
  17. 2018 Low

    Proposed that RAGE-mediated endocytosis delivers HMGB1 and its bound cargo to the endolysosome, where HMGB1 destabilizes membranes to reach cytosolic pattern recognition receptors.

    Evidence Review summarizing RAGE endocytosis and lysosomal destabilization assays

    PMID:29530410

    Open questions at the time
    • Review-level, lacking detailed primary experimental description
    • Membrane destabilization mechanism not biochemically defined
  18. 2019 Medium

    Connected ferroptotic HMGB1 release to autophagy and HDAC inhibition-driven acetylation, with RAGE rather than TLR4 mediating downstream inflammation.

    Evidence ATG5/ATG7 KO, autophagy inhibitors, HDAC assays, receptor-specific macrophage stimulation

    PMID:30686534

    Open questions at the time
    • Single lab
    • Mechanism linking autophagy to HDAC activity not resolved
  19. 2020 High

    Dissected secretion from inflammasome activation, showing macrophage HMGB1 release requires pyroptotic lysis while in vivo release can proceed independently of gasdermin D.

    Evidence Gasdermin D KO macrophages and mice separating pyroptosis from inflammasome activation

    PMID:32917873

    Open questions at the time
    • Pyroptosis-independent in vivo release route not identified
    • Cell types responsible in vivo not defined
  20. 2021 High

    Established a required role for nociceptor-derived HMGB1 in neurogenic inflammation by direct optogenetic release and neuron-specific knockout.

    Evidence Channelrhodopsin-2 nociceptor stimulation and Syn-Cre HMGB1 conditional KO in nerve injury and arthritis models

    PMID:34385304

    Open questions at the time
    • Receptor mediating neuronal HMGB1 effects not defined here
    • Redox form of neuron-released HMGB1 unknown
  21. 2022 Medium

    Added a phosphorylation-based release route, showing AMPK phosphorylates HMGB1 during cuproptosis to drive RAGE-dependent inflammation.

    Evidence AMPK knockdown/inhibition, HMGB1 phosphorylation analysis, AGER-dependent cytokine assays

    PMID:36211458

    Open questions at the time
    • Single lab
    • AMPK phosphorylation site on HMGB1 not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the nuclear, autophagic, and extracellular roles of HMGB1 are integrated in vivo, and how its post-translational/redox states are coordinately switched within a given cellular context, remains unresolved.
  • No unified structural model linking redox state, modifications, and receptor choice
  • Pyroptosis-independent in vivo release mechanism unidentified
  • Quantitative control of nuclear retention vs secretion in physiological settings unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0048018 receptor ligand activity 2 GO:0008092 cytoskeletal protein binding 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005576 extracellular region 4 GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005764 lysosome 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 3 R-HSA-73894 DNA Repair 2
Partners
AGERBECN1C1QCXCL12SRCTLR4TLR5TP53

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 HMGB1 (HMG1) HMG-box domain recognizes and binds four-way junction DNA structures (cross-shaped DNA with ~60° and ~120° angles between arms) in a structure-specific, sequence-independent manner, and binding to linear duplex DNA containing the SRY target sequence produces a sharp DNA bend. In vitro DNA binding assays with four-way junction DNA and linear duplex DNA; gel mobility shift and footprinting experiments The EMBO journal High 1425584
1979 HMG1 unwinds the DNA double helix by local denaturation of base pairs; it has higher affinity for single-stranded than double-stranded DNA and introduces a net unwinding angle of ~22° per molecule. In absence of salt, HMG1 stabilizes DNA; in presence of salt, it destabilizes DNA. DNA melting absorption technique; competition unwinding experiments measuring topological winding numbers Nucleic acids research High 226939
1994 The acidic C-terminal tail of HMGB1 downregulates the DNA-binding and supercoiling activities of the tandem HMG-box domains (HMG3) in an ionic strength-dependent manner; removal of the tail increases DNA affinity and supercoiling activity. The tandem HMG-box domains can loop, compact, and change topology of DNA. The acidic tail directly modulates DNA-binding domain specificity. DNA supercoiling assays with topoisomerase I; electron microscopy of DNA-protein complexes; comparison of HMG1 vs. tryptic HMG3 (tail-deleted form) Nucleic acids research High 8152909
1998 HMGB1 (HMG-1) directly binds p53 protein in vitro and enhances p53 DNA-binding activity, including that of a constitutively active C-terminally deleted p53 (p53Δ30), by a mechanism distinct from other known p53 activators. HMG-1 promotes assembly of higher-order p53 nucleoprotein structures and stimulates p53-mediated transactivation in vivo. Biochemical purification from HeLa nuclear extracts; recombinant His-tagged HMG-1 in vitro binding and DNA-binding assays; transient transfection transactivation assays Genes & development High 9472015
1999 HMG1 domain B binds cisplatin-modified DNA with high affinity (Kd ~60 nM) and induces a bend angle of 80–95° in the cisplatin-modified DNA, as determined by FRET distance measurements. Kinetic parameters: kon = 1.1 × 10⁹ M⁻¹s⁻¹, koff = 30 s⁻¹. Fluorescence resonance energy transfer (FRET) with fluorescein/rhodamine-labeled DNA probes; fluorescence titration; stopped-flow fluorescence spectroscopy The Journal of biological chemistry High 10212205
2000 HMGB1 stimulates DNA end joining (both cohesive-end and blunt-end ligation by T4 DNA ligase) by physically associating two DNA molecules via their ends. This activity requires the B domain of HMGB1, specifically the C-terminal flanking basic residues and conserved basic/hydrophobic residues within the HMG box. In vitro ligation assay with T4 DNA ligase; pull-down assays; electron microscopy and scanning force microscopy of DNA-protein complexes; domain deletion/mutation analysis European journal of biochemistry High 10866811
2007 The acidic C-terminal tail of HMGB1 directly interacts with the N-terminal HMG-box domains (confirmed by NMR), and this intramolecular interaction can be competed more efficiently by four-way junction DNA than by linear dsDNA. Mutations in the N-terminal region that disrupt C-tail binding abolish HMGB1's ability to distinguish linear DNA from four-way junction DNA, defining a mechanism by which the acidic tail enhances domain specificity for structured DNAs. NMR; competitive DNA-binding assays; site-directed mutagenesis of the N-terminal region Biochemical and biophysical research communications High 17585880
2010 Endogenous HMGB1 directly interacts with the autophagy protein Beclin1 and displaces Bcl-2 from Beclin1, thereby enhancing autophagic flux. Reactive oxygen species promote cytosolic translocation of HMGB1. Mutation of C106 (but not C23 or C45) promotes cytosolic HMGB1 localization and sustained autophagy. The intramolecular disulfide bond between C23 and C45 is required for HMGB1 binding to Beclin1 and sustaining autophagy. Co-immunoprecipitation; direct protein interaction assays; site-directed mutagenesis of cysteine residues; pharmacological inhibition (ethyl pyruvate); autophagy flux measurement; HMGB1 knockout/knockdown cells The Journal of cell biology High 20819940
2012 PKR (double-stranded RNA-dependent protein kinase) physically interacts with multiple inflammasome components (NLRP3, NLRP1, NLRC4, AIM2) and is required for inflammasome activation; PKR autophosphorylation in a cell-free reconstituted system with recombinant NLRP3, ASC, and pro-caspase-1 is sufficient to reconstitute inflammasome activity, leading to HMGB1 release. PKR deficiency severely impairs HMGB1 secretion in response to diverse inflammasome agonists. Genetic deletion and pharmacological inhibition of PKR; Co-IP of PKR with inflammasome components; cell-free reconstitution with recombinant proteins; in vivo peritonitis model measuring HMGB1 secretion Nature High 22801494
2012 HMGB1 and p53 form a complex that reciprocally regulates autophagy and apoptosis. p53 knockout increases cytosolic HMGB1 expression and induces autophagy; HMGB1 knockout increases p53 cytoplasmic localization and decreases autophagy. p53 acts as a negative regulator of the HMGB1/Beclin1 complex. The HMGB1/p53 complex affects the cytoplasmic localization of the reciprocal binding partner. Co-immunoprecipitation; genetic knockout of p53 (HCT116) and HMGB1 (MEFs); subcellular fractionation; autophagy measurement Cancer research Medium 22345153
2014 PARP-1 regulates LPS-induced HMGB1 translocation and release from macrophages by two mechanisms: (1) PARylating HMGB1 to facilitate its subsequent acetylation, and (2) increasing the HAT/HDAC activity ratio to promote HMGB1 acetylation. PARylated HMGB1 remains nuclear, whereas acetylated HMGB1 localizes to the cytoplasm. Genetic or pharmacological inhibition of PARP-1 suppresses HMGB1 acetylation, nuclear-to-cytoplasm translocation, and extracellular release. ROS and ERK signaling upstream of PARP activation are also required. Genetic PARP-1 depletion and PARP inhibitors in bone marrow-derived macrophages; in vitro enzymatic PARylation reaction; HAT/HDAC activity assays; subcellular fractionation; immunofluorescence Journal of immunology High 25392528
2013 The inflammatory activity of extracellular HMGB1 depends on its redox state: an intramolecular disulfide bond between C23 and C45 combined with a reduced C106 confers cytokine/TLR4-stimulating activity. Oxidation of C106 blocks stimulatory activity and promotes immune tolerance. Thus the chemoattractant and cytokine-inducing activities of HMGB1 are separable and depend on distinct cysteine redox states. Redox state characterization with defined recombinant HMGB1 isoforms; TLR4 activation assays; leukocyte recruitment assays Antioxidants & redox signaling Medium 23373897
2012 The chemoattractant activity of HMGB1 is entirely mediated through formation of a heterocomplex with the chemokine CXCL12, which acts on CXCR4 more potently than CXCL12 alone. Only the all-thiol (fully reduced) form of HMGB1 can form this heterocomplex with CXCL12. The disulfide HMGB1 (C23–C45 bond) activates TLR4 to induce cytokine release but cannot recruit leukocytes, demonstrating that chemoattractant and cytokine-inducing activities of HMGB1 are separable redox-dependent functions. Biochemical characterization of HMGB1-CXCL12 complex; receptor binding assays on CXCR4; leukocyte migration assays with distinct redox isoforms Molecular immunology High 23207101
2010 HMGB1 acts as a cofactor in base excision repair (BER), inhibiting single-nucleotide BER and stimulating long-patch BER by modulating the activities of BER enzymes. HMGB1 was found cross-linked to a BER intermediate in cells, indicating direct participation in the BER pathway. In vitro BER assays; cross-linking of HMGB1 to BER intermediates; enzymatic activity measurements of BER enzymes in presence/absence of HMGB1 Biochimica et biophysica acta Medium 20123074
2016 TLR5 is an HMGB1 receptor. HMGB1 binds TLR5 and initiates NF-κB signaling via MyD88-dependent signaling, resulting in proinflammatory cytokine production and pain hypersensitivity in vivo. The C-terminal tail region of HMGB1 is essential for its interaction with TLR5. Biophysical binding assays; in vitro NF-κB signaling assays with TLR5-expressing cells; in vivo allodynia model; C-terminal tail truncation analysis Cell reports Medium 27760316
2019 HMGB1 is released by ferroptotic cells in an autophagy-dependent manner. Genetic ablation (ATG5-/- or ATG7-/- cells) or pharmacological inhibition of autophagy blocks ferroptosis-induced HMGB1 release. Autophagy-mediated HDAC inhibition promotes HMGB1 acetylation leading to its release during ferroptosis. AGER (RAGE), but not TLR4, is required for HMGB1-mediated inflammation in macrophages in response to ferroptotic cells. Genetic KO of ATG5/ATG7; pharmacological autophagy inhibitors; HMGB1 release measurement; HDAC inhibition assays; receptor-specific macrophage stimulation assays Biochemical and biophysical research communications Medium 30686534
2020 HMGB1 release after inflammasome activation in macrophages occurs only under conditions causing cell lysis (pyroptosis), not during inflammasome activation per se. When pyroptosis is prevented, HMGB1 is not released despite inflammasome activation and IL-1β secretion. Gasdermin D knockout mice secrete HMGB1 normally during endotoxemia (indirect/pyroptosis-independent mechanism in vivo), while IL-1β secretion is completely blocked. Genetic gasdermin D knockout macrophages; LPS stimulation; separation of pyroptosis from inflammasome activation; measurement of HMGB1 and IL-1β secretion in vitro and in vivo Nature communications High 32917873
2022 During cuproptosis, copper accumulation-induced ATP depletion activates AMPK, which phosphorylates HMGB1 to promote its extracellular release. Genetic or pharmacological inhibition of AMPK limits cuproptosis-associated HMGB1 release. Extracellular HMGB1 from cuproptotic cells signals through AGER (RAGE) to induce inflammatory cytokine production; HMGB1-deficient cuproptotic cells show greatly reduced AGER-dependent inflammatory signaling. RNAi knockdown of AMPK; pharmacological AMPK inhibition (dorsomorphin); HMGB1 phosphorylation analysis; AGER-dependent cytokine production assays; cuproptosis inducers Frontiers in cell and developmental biology Medium 36211458
2011 Intracellular HMGB1 negatively regulates efferocytosis (phagocytosis of apoptotic cells). HMGB1 knockdown in macrophages and fibroblasts increases phagocytosis of apoptotic cells, enhances Rac-1 activation and cytoskeletal rearrangement, and increases phosphorylation of ERK and FAK. HMGB1 physically interacts with Src kinase and inhibits Src-FAK interactions; in vitro, purified HMGB1 directly diminishes interactions between purified FAK and Src. HMGB1 siRNA knockdown; phagocytosis assays; Rac-1 activation assay; phosphorylation analysis; Src inhibition; in vitro pulldown of purified FAK and Src with/without HMGB1 Journal of immunology Medium 21957148
2021 Nociceptors directly release HMGB1 upon activation: transgenic nociceptors expressing channelrhodopsin-2 release HMGB1 in response to light stimulation. Neuron-specific HMGB1 silencing (Syn-Cre × HMGB1f/f mice) protects against cutaneous inflammation, allodynia after sciatic nerve injury, and joint inflammation in collagen antibody-induced arthritis, establishing a required role for nociceptor-derived HMGB1 in neurogenic inflammation. Optogenetic stimulation of channelrhodopsin-2-expressing nociceptors; conditional neuron-specific HMGB1 knockout (Syn-Cre/HMGB1fl/fl); sciatic nerve injury model; collagen antibody-induced arthritis model Proceedings of the National Academy of Sciences of the United States of America High 34385304
1994 The mouse hmg1 gene contains five exons (first untranslated), with a promoter coinciding with a CpG island and lacking a TATA sequence, consistent with ubiquitous expression. No evidence for a membrane localization signal was found in the coding sequence. Gene isolation, sequencing, exon mapping; reporter gene expression assays; Southern blot analysis The Journal of biological chemistry Medium 7961836
2016 C1q and HMGB1 cooperate via a complex involving RAGE and LAIR-1 to induce monocyte differentiation into anti-inflammatory M2-like macrophages, counterbalancing HMGB1's pro-inflammatory M1-inducing activity. This pathway depends on the relative levels of C1q and HMGB1. In vitro monocyte differentiation assays; receptor blocking experiments (RAGE and LAIR-1); co-stimulation with C1q and HMGB1 Blood Medium 27683415
2018 Extracellular HMGB1 can be internalized via RAGE-receptor-mediated endocytosis into the endolysosomal compartment while bound to other extracellular proinflammatory molecules. After endocytosis, HMGB1 destabilizes lysosomal membranes, facilitating access of HMGB1-bound partner molecules to endosomal and cytosolic pattern recognition receptors. RAGE-dependent endocytosis assays; lysosomal membrane destabilization assays; co-internalization experiments with HMGB1 and bound molecules Seminars in immunology Low 29530410
2010 HMGB1 acts as a cofactor in base excision repair, stimulating long-patch BER sub-pathway while inhibiting single-nucleotide BER, thereby directing repair toward long-patch BER, which can result in trinucleotide repeat instability. In vitro BER assays; cross-linking of HMGB1 to BER intermediates Biochimica et biophysica acta Medium 20123074

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 HMGB1 and RAGE in inflammation and cancer. Annual review of immunology 1223 20192808
2010 Endogenous HMGB1 regulates autophagy. The Journal of cell biology 815 20819940
2014 HMGB1 in health and disease. Molecular aspects of medicine 784 25010388
2022 The mechanism of HMGB1 secretion and release. Experimental & molecular medicine 669 35217834
2008 HMGB1: endogenous danger signaling. Molecular medicine (Cambridge, Mass.) 660 18431461
2012 Novel role of PKR in inflammasome activation and HMGB1 release. Nature 640 22801494
2012 HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nature reviews. Rheumatology 601 22293756
2019 The release and activity of HMGB1 in ferroptosis. Biochemical and biophysical research communications 539 30686534
2001 HMG1 and 2, and related 'architectural' DNA-binding proteins. Trends in biochemical sciences 535 11246022
2020 Targeting Inflammation Driven by HMGB1. Frontiers in immunology 525 32265930
2007 High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunological reviews 511 17979838
2005 The cytokine activity of HMGB1. Journal of leukocyte biology 454 15734795
2013 HMGB1 in cancer: good, bad, or both? Clinical cancer research : an official journal of the American Association for Cancer Research 417 23723299
1992 SRY, like HMG1, recognizes sharp angles in DNA. The EMBO journal 401 1425584
2004 Extracellular role of HMGB1 in inflammation and sepsis. Journal of internal medicine 369 14871456
2009 HMGB1 loves company. Journal of leukocyte biology 349 19414536
2009 Targeting HMGB1 in inflammation. Biochimica et biophysica acta 306 19948257
2006 High-mobility group box 1 (HMGB1) protein: friend and foe. Cytokine & growth factor reviews 299 16513409
2023 The multifunctional protein HMGB1: 50 years of discovery. Nature reviews. Immunology 293 37322174
2015 High Mobility Group Box Protein 1 (HMGB1): The Prototypical Endogenous Danger Molecule. Molecular medicine (Cambridge, Mass.) 289 26605648
2013 An overview on HMGB1 inhibitors as potential therapeutic agents in HMGB1-related pathologies. Pharmacology & therapeutics 288 24220159
2005 HMGB1: guiding immunity from within. Trends in immunology 287 15978523
1998 High mobility group protein-1 (HMG-1) is a unique activator of p53. Genes & development 281 9472015
2018 High-mobility group box 1 protein (HMGB1) operates as an alarmin outside as well as inside cells. Seminars in immunology 248 29530410
2020 HMGB1 in inflammation and cancer. Journal of hematology & oncology 245 32831115
2002 HMGB1 as a DNA-binding cytokine. Journal of leukocyte biology 240 12488489
2020 HMGB1 as a therapeutic target in disease. Journal of cellular physiology 238 33107103
2012 p53/HMGB1 complexes regulate autophagy and apoptosis. Cancer research 220 22345153
2016 HMGB1 as biomarker and drug target. Pharmacological research 215 27378565
2015 Oxidative stress-mediated HMGB1 biology. Frontiers in physiology 214 25904867
2001 HMG1 and 2: architectural DNA-binding proteins. Biochemical Society transactions 211 11497996
2010 HMGB1, a potent proinflammatory cytokine in sepsis. Cytokine 186 20347329
1995 The HMG-1 box protein family: classification and functional relationships. Nucleic acids research 183 7784217
2020 Indirect regulation of HMGB1 release by gasdermin D. Nature communications 178 32917873
2012 HMGB1 and leukocyte migration during trauma and sterile inflammation. Molecular immunology 178 23207101
2020 High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies. Journal of hematology & oncology 165 32660524
2007 HMGB1: a signal of necrosis. Autoimmunity 158 17516211
2008 High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheumatic disease. Arthritis research & therapy 152 18598385
1992 DNA binding properties of an HMG1-related protein from yeast mitochondria. The Journal of biological chemistry 151 1737791
2019 Enlightening the role of high mobility group box 1 (HMGB1) in inflammation: Updates on receptor signalling. European journal of pharmacology 148 31229535
2016 C1q and HMGB1 reciprocally regulate human macrophage polarization. Blood 145 27683415
2013 Regulation of HMGB1 release by inflammasomes. Protein & cell 141 23483477
2004 HMGB1 is a potent trigger of arthritis. Journal of internal medicine 139 14871458
1994 DNA looping by the HMG-box domains of HMG1 and modulation of DNA binding by the acidic C-terminal domain. Nucleic acids research 139 8152909
2013 Redox modulation of HMGB1-related signaling. Antioxidants & redox signaling 137 23373897
2006 HMGB1, a novel inflammatory cytokine. Clinica chimica acta; international journal of clinical chemistry 130 16979611
2004 Extracellular HMGB1 as a proinflammatory cytokine. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 125 15212706
2001 HMG-1 rediscovered as a cytokine. Shock (Augusta, Ga.) 124 11303722
2004 Recombinant HMGB1 with cytokine-stimulating activity. Journal of immunological methods 121 15251426
2016 HMGB1 Activates Proinflammatory Signaling via TLR5 Leading to Allodynia. Cell reports 119 27760316
2016 Regulation of Posttranslational Modifications of HMGB1 During Immune Responses. Antioxidants & redox signaling 114 26715031
2006 Role of HMGB1 in cardiovascular diseases. Current opinion in pharmacology 110 16487750
2002 HMGB1 as a cytokine and therapeutic target. Journal of endotoxin research 107 12697092
2001 Dual roles for HMGB1: DNA binding and cytokine. Journal of endotoxin research 105 11717586
2010 HMGB1: roles in base excision repair and related function. Biochimica et biophysica acta 103 20123074
2011 HMGB1 release by inflammasomes. Virulence 101 21422809
2010 The role of HMGB1 in the pathogenesis of rheumatic disease. Biochimica et biophysica acta 101 20123076
2014 PARP-1 mediates LPS-induced HMGB1 release by macrophages through regulation of HMGB1 acetylation. Journal of immunology (Baltimore, Md. : 1950) 99 25392528
2012 H1 and HMGB1: modulators of chromatin structure. Biochemical Society transactions 94 22435809
1979 Nonhistone proteins HMG1 and HMG2 unwind DNA double helix. Nucleic acids research 94 226939
2016 Ds-HMGB1 and fr-HMGB induce depressive behavior through neuroinflammation in contrast to nonoxid-HMGB1. Brain, behavior, and immunity 93 27647532
2003 HMGB1 in sepsis. Scandinavian journal of infectious diseases 90 14620138
1992 Three genes encode 3-hydroxy-3-methylglutaryl-coenzyme A reductase in Hevea brasiliensis: hmg1 and hmg3 are differentially expressed. Plant molecular biology 90 1377968
2014 Emerging role of HMGB1 in fibrotic diseases. Journal of cellular and molecular medicine 87 25284457
2008 HMGB1 is a bone-active cytokine. Journal of cellular physiology 84 17786958
2018 High Mobility Group Box-1 (HMGb1): Current Wisdom and Advancement as a Potential Drug Target. Journal of medicinal chemistry 82 29268019
2021 HMGB1 released from nociceptors mediates inflammation. Proceedings of the National Academy of Sciences of the United States of America 79 34385304
2018 HMGB1 and repair: focus on the heart. Pharmacology & therapeutics 79 30529040
2012 HMGB-1 as a target for inflammation controlling. Recent patents on endocrine, metabolic & immune drug discovery 79 22845335
2019 High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis: from pathogenesis to therapeutic approaches. Journal of neurochemistry 78 30644560
2012 HMGB1 and its physiological and pathological roles. Bratislavske lekarske listy 74 22428766
2021 YAP promotes autophagy and progression of gliomas via upregulating HMGB1. Journal of experimental & clinical cancer research : CR 73 33726796
1999 Interactions between an HMG-1 protein and members of the Rel family. Proceedings of the National Academy of Sciences of the United States of America 71 10485885
2014 HMGB1-dependent and -independent autophagy. Autophagy 70 25126737
2022 HMGB1 is a mediator of cuproptosis-related sterile inflammation. Frontiers in cell and developmental biology 69 36211458
2017 HMGB1 redox during sepsis. Redox biology 69 28806702
1994 The mouse gene coding for high mobility group 1 protein (HMG1). The Journal of biological chemistry 68 7961836
1994 Prokaryotic HU and eukaryotic HMG1: a kinked relationship. Molecular microbiology 65 7830547
2009 The translocation of HMGB1 during cell activation and cell death. Autoimmunity 64 19811282
2015 The Role of HMGB1 in Radioresistance of Bladder Cancer. Molecular cancer therapeutics 62 26719575
2022 High-mobility group box 1 (HMGB1) in COVID-19: extrapolation of dangerous liaisons. Inflammopharmacology 60 35471628
2006 HMGB1 expression and release by bone cells. Journal of cellular physiology 60 16419037
2023 HMGB1 in the interplay between autophagy and apoptosis in cancer. Cancer letters 59 38007142
1999 Structural and kinetic studies of a cisplatin-modified DNA icosamer binding to HMG1 domain B. The Journal of biological chemistry 59 10212205
2011 Intracellular HMGB1 negatively regulates efferocytosis. Journal of immunology (Baltimore, Md. : 1950) 56 21957148
2020 HMGB1 in Systemic Lupus Erythematosus. Frontiers in immunology 55 32536928
2018 Blockade of HMGB1 Attenuates Diabetic Nephropathy in Mice. Scientific reports 55 29844451
2019 High Mobility Group Box-1 (HMGB1): A Potential Target in Therapeutics. Current drug targets 49 31215389
2008 Is HMGB1 an osteocyte alarmin? Journal of cellular biochemistry 49 17948903
2011 HMGB1, an alarmin promoting HIV dissemination and latency in dendritic cells. Cell death and differentiation 48 22033335
2000 HMG1 protein stimulates DNA end joining by promoting association of DNA molecules via their ends. European journal of biochemistry 48 10866811
2015 Association between HMGB1 and COPD: A Systematic Review. Mediators of inflammation 46 26798204
2007 The HMGB1 acidic tail regulates HMGB1 DNA binding specificity by a unique mechanism. Biochemical and biophysical research communications 46 17585880
2021 HMGB1 Mediated Inflammation and Autophagy Contribute to Endometriosis. Frontiers in endocrinology 45 33815277
2017 Identification of pharmacological agents that induce HMGB1 release. Scientific reports 44 29097772
2013 Increased HMGB1 serum levels and altered HMGB1 expression in patients with psoriasis vulgaris. Archives of dermatological research 42 23440398
1998 Linker histones versus HMG1/2: a struggle for dominance? BioEssays : news and reviews in molecular, cellular and developmental biology 42 9723008
2020 HMGB1 in kidney diseases. Life sciences 38 32781069
1997 Recombinant HMG1 protein produced in Pichia pastoris: a nonviral gene delivery agent. BioTechniques 37 9105624
2022 HMGB1/TLR4 induces autophagy and promotes neuroinflammation after intracerebral hemorrhage. Brain research 35 35820449

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