Affinage

S100B

Protein S100-B · UniProt P04271

Length
92 aa
Mass
10.7 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 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

S100B is a Ca2+-binding EF-hand protein that operates as a dual-compartment signaling molecule, acting intracellularly to engage target proteins and extracellularly as a secreted ligand for the RAGE receptor (PMID:17660747, PMID:20587415). Structurally it assembles beyond the homodimer into a tetrameric/octameric architecture, and the higher-order tetramer binds two RAGE molecules through the receptor V-domain with greater affinity than the dimer and drives stronger growth/survival signaling (PMID:17660747). Intracellularly, Ca2+-dependent binding partners include p53—where S100B sequesters wild-type p53 to suppress its phosphorylation, target-gene induction (p21, PIDD), and Fas-mediated apoptosis in melanoma, an interaction that can be pharmacologically disrupted to restore p53 pro-apoptotic control (PMID:20587415, PMID:32022398)—as well as the metabolic enzyme phosphoglucomutase (which S100B stimulates), annexin VI, and the vimentin intermediate-filament and microtubule networks, consistent with roles in cytoskeletal dynamics (PMID:8894274, PMID:11108963, PMID:10326676). Extracellular S100B signals through RAGE to activate NF-κB, ERK1/2, and parallel Cdc42-Rac1-JNK and Ras-Rac1 cascades, inducing COX-2, iNOS/NO production, and inflammatory mediators that drive microglial/macrophage M1 polarization and context-dependent neurotoxicity or neuroprotection (PMID:17660747, PMID:9375660, PMID:17023559, PMID:30229393, PMID:15584905). S100B also acts as a Ca2+-dependent chaperone that suppresses Aβ42 primary and secondary nucleation by binding monomers, oligomers, and fibrils, protecting cells from amyloid toxicity (PMID:29963623). As a secreted neurotrophic factor lacking a signal peptide, S100B is exported via calsyntenin 3β from thermogenic adipocytes to promote sympathetic innervation of adipose tissue (PMID:31043739). Its transcription is cell-type-specifically controlled by SOX10 in Schwann cells (where S100B supports myelination), the SOX9/SOX5/SOX6 trio in chondrocytes (where it restrains hypertrophic differentiation), alpha1-adrenergic/PKC signaling in cardiomyocytes (where it serves as a negative-feedback brake on hypertrophy), and a YAP/TAZ-PRDM16-C/EBPβ axis in adipocytes (PMID:12388300, PMID:9677434, PMID:37925548, PMID:25536222, PMID:17396138).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1994 Medium

    Established that S100B dosage in vivo drives glial and neuronal remodeling, framing it as an active modulator of brain tissue architecture rather than a passive marker.

    Evidence S100B transgenic mice with 2- and 7-fold elevation, with quantitative glial/neuronal markers and hippocampal histology

    PMID:8202493

    Open questions at the time
    • Does not distinguish intracellular versus secreted S100B effects
    • Mechanism linking S100B to astrocytosis/axonal sprouting not defined
  2. 1996 Medium

    Identified the first intracellular Ca2+-dependent enzyme target, showing S100B is a regulator of metabolic enzyme activity and that S100 paralogs can have opposite functional effects.

    Evidence Reciprocal affinity chromatography, gel overlay, and phosphoglucomutase enzyme activity assay

    PMID:8894274

    Open questions at the time
    • In vitro only; cellular relevance not tested
    • Binding interface on S100B not mapped
  3. 1997 High

    Demonstrated that extracellular S100B is neurotoxic through an astrocyte iNOS/NO intermediary, defining a non-cell-autonomous toxicity pathway.

    Evidence Astrocyte-neuron co-culture with NOS-inhibitor rescue and multiple cell-death readouts

    PMID:9375660

    Open questions at the time
    • Receptor mediating S100B uptake/signaling not identified in this study
    • Concentration threshold for toxic versus trophic effect not resolved
  4. 1999 Medium

    Linked S100B to the cytoskeleton and apoptotic machinery, showing intracellular association with vimentin/microtubule networks and Bcl-2-dependent control of S100B-induced death.

    Evidence Immunogold EM with colchicine perturbation in myoblasts; bcl-2 gain/loss-of-function with apoptosis assays in neuronal precursors

    PMID:10326676 PMID:10381557

    Open questions at the time
    • Direct biochemical binding to filaments not confirmed in localization study
    • How S100B engages the Bcl-2 axis mechanistically not defined
  5. 2002 Medium

    Resolved how S100B transcription is induced in the heart, establishing it as an alpha1A-adrenergic/PKC-driven negative-feedback brake on cardiomyocyte hypertrophy.

    Evidence Promoter deletion/luciferase analysis with adrenergic agonists/antagonists in cardiac myocytes; transgenic and forced-expression studies

    PMID:12388300 PMID:9677434

    Open questions at the time
    • Whether the anti-hypertrophic effect is intracellular or RAGE-mediated unresolved at this stage
    • TEF-1/RTEF-1 regulatory logic not connected to downstream effectors
  6. 2006 Medium

    Dissected the extracellular S100B-RAGE signaling branch, showing it activates two parallel cascades (Cdc42-Rac1-JNK and Ras-Rac1-NF-κB) to induce COX-2 in microglia.

    Evidence Microglial culture with RAGE-dependent and pathway-specific inhibitor studies, Western blot and reporter assays

    PMID:17023559

    Open questions at the time
    • Not independently replicated
    • Relative contribution of each cascade to inflammatory output not quantified
  7. 2007 High

    Provided the structural basis for ligand potency, showing S100B forms an octamer/tetramer that binds RAGE at higher affinity than the dimer and triggers stronger growth signaling.

    Evidence X-ray crystallography, analytical ultracentrifugation, and cell growth/survival assays

    PMID:17660747

    Open questions at the time
    • In vivo relevance of higher-order oligomers not established
    • Downstream signaling differences between oligomeric states not mapped
  8. 2010 High

    Defined a key intracellular oncogenic mechanism: S100B binds and suppresses p53 to block apoptosis in melanoma, and a RAGE/ERK1/p53 extracellular branch drives apoptosis in cardiomyocytes.

    Evidence siRNA, gain-of-function, and pifithrin-alpha rescue in melanoma cells; S100B knockout mouse with post-MI phenotyping and signaling readouts

    PMID:20204434 PMID:20587415

    Open questions at the time
    • Structural detail of the S100B-p53 interface not resolved here
    • Why the same protein is anti-apoptotic intracellularly yet pro-apoptotic via RAGE is unresolved
  9. 2014 High

    Established cell-type-specific transcriptional control by SOX factors, with SOX10 driving S100B in Schwann cells to support myelination and restrain proliferation.

    Evidence SOX10 overexpression/knockdown, promoter SOX-motif mapping, and DRG myelination co-culture; SOX trio ChIP/EMSA in chondrocytes

    PMID:17396138 PMID:25536222

    Open questions at the time
    • Downstream effectors of S100B in myelination/chondrocyte differentiation not defined
    • Whether S100B acts intra- or extracellularly in these contexts not resolved
  10. 2018 High

    Revealed a Ca2+-dependent chaperone function: S100B suppresses Aβ42 primary and secondary nucleation by binding monomers, oligomers, and fibrils, protecting cells from amyloid toxicity.

    Evidence NMR mapping of the interaction site, thioflavin-T aggregation kinetics, and cell viability assays

    PMID:29963623

    Open questions at the time
    • In vivo protective relevance in amyloid pathology not tested
    • Whether the chaperone role competes with RAGE-driven inflammation in situ unknown
  11. 2019 High

    Identified the mechanism of S100B secretion and its trophic action, showing calsyntenin 3β drives ER localization/secretion of signal-peptide-lacking S100B to promote sympathetic innervation of fat.

    Evidence Adipocyte loss/gain-of-function with genetic epistasis (KO phenocopy plus rescue) and in vitro neurite outgrowth assay

    PMID:31043739

    Open questions at the time
    • Receptor mediating S100B's neurotrophic effect on sympathetic neurons not identified
    • Unconventional secretion route mechanistics beyond calsyntenin 3β dependence not detailed
  12. 2023 High

    Resolved upstream transcriptional gating in adipocytes, showing YAP/TAZ repress S100B by competing with C/EBPβ for PRDM16, with adrenergic signaling releasing repression to permit beige-fat innervation.

    Evidence Adipocyte Yap/Taz knockout, AAV-S100B rescue, co-IP of YAP/TAZ-PRDM16-C/EBPβ, and transcriptional reporters

    PMID:37925548

    Open questions at the time
    • How adrenergic phosphorylation of YAP/TAZ is integrated with other S100B promoters not connected across tissues
    • Quantitative contribution to systemic thermogenesis not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single Ca2+-binding protein is partitioned between opposing intracellular (pro-survival, p53-suppressing, chaperone) and extracellular (RAGE-driven, often pro-inflammatory/cytotoxic) functions across cell types and concentrations remains unresolved.
  • No unified model linking oligomeric state, concentration, and secretion to functional outcome
  • RAGE-independent extracellular mechanisms (e.g., CCL2 in glioma) incompletely mapped
  • In vivo balance of neurotoxic versus neuroprotective S100B not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0048018 receptor ligand activity 2 GO:0044183 protein folding chaperone 1
Localization
GO:0005576 extracellular region 3 GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3
Partners
ANXA6CLSTN3PGM1PRDM16RAGESTEAP4TP53

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 X-ray crystal structure of human Ca2+-loaded S100B at 1.9 Å resolution revealed an octameric architecture of four homodimeric units arranged as two tetramers. Tetrameric S100B binds RAGE with higher affinity than dimeric S100B, and analytical ultracentrifugation showed the tetramer binds two RAGE molecules via the V-domain. Tetrameric S100B caused stronger activation of cell growth and survival than dimeric S100B. X-ray crystallography, size-exclusion chromatography, analytical ultracentrifugation, cell growth/survival assays The EMBO journal High 17660747
1997 High concentrations of S100beta treatment of astrocytes activates inducible nitric oxide synthase (iNOS) and causes NO release; in astrocyte-neuron co-cultures, this S100beta-induced NO from astrocytes caused neuronal cell death (both necrosis and apoptosis). Neuronal death was blocked by a specific NOS inhibitor, establishing that S100B acts through iNOS/NO in astrocytes to cause neurotoxicity. Astrocyte-neuron co-culture, NOS inhibitor pharmacology, cell death assays (propidium iodide, TUNEL, apoptosis morphology) Journal of neurochemistry High 9375660
2018 S100B suppresses Aβ42 aggregation in a calcium-dependent manner. NMR experiments showed that the interaction occurs at a promiscuous peptide-binding region within the interfacial cleft of the S100B homodimer; calcium binding to S100B favors interaction with monomeric Aβ42, possibly inducing an α-helical conformer that locks aggregation. S100B delays onset of Aβ42 aggregation by inhibiting primary nucleation and inhibits fibril surface-catalyzed secondary nucleation by binding oligomers and fibrils. S100B protected cells from Aβ42-mediated toxicity. NMR spectroscopy, thioflavin-T aggregation kinetics assays, cell viability/apoptosis assays Science advances High 29963623
2010 S100B forms a complex with p53 in malignant melanoma cells (C8146A). siRNA knockdown of S100B increased p53 protein, phosphorylated p53, and p53 target gene products (p21, PIDD) without changing p53 mRNA, and restored p53-dependent apoptosis via the Fas death receptor pathway (caspase 3/8 activation, PARP cleavage). Rescue with pifithrin-alpha (p53 inhibitor) reversed siRNA(S100B)-induced apoptosis, confirming the mechanism. Introduction of S100B into S100B-null cells reduced UV-induced apoptosis 7-fold. siRNA knockdown, Western blot, caspase activation assays, DNA laddering, flow cytometry, p53 inhibitor rescue The Journal of biological chemistry High 20587415
2006 Extracellular S100B up-regulates cyclooxygenase-2 (COX-2) expression in microglia via RAGE in a concentration-dependent manner. Two independent downstream pathways were identified: a Cdc42-Rac1-JNK pathway and a Ras-Rac1-NF-κB pathway, both activated independently by S100B-RAGE signaling. Microglial cell culture, RAGE-dependent pharmacological inhibition, pathway inhibitor studies, Western blot, reporter assays Journal of leukocyte biology Medium 17023559
1996 Phosphoglucomutase was identified as an intracellular S100B (and S100A1) target protein. S100B bound phosphoglucomutase-Sepharose in a calcium-dependent manner (confirmed by reciprocal affinity chromatography and gel overlay). S100B stimulated phosphoglucomutase activity in a calcium-dependent manner, in contrast to S100A1 which inhibited it. Other calcium-binding proteins (calmodulin, troponin C, parvalbumin, α-lactalbumin) had no effect. Gel overlay, affinity chromatography (reciprocal), enzyme activity assay Cell calcium Medium 8894274
2000 S100A1 and S100B bind annexin VI in a Ca2+-dependent manner, forming heterotetramers in which an S100 homodimer crossbridges two copies of annexin VI. The C-terminal half of annexin VI (annexin VI-b), but not the N-terminal half (annexin VI-a), blocks the inhibitory effect of S100A1 and S100B on intermediate filament assembly. The C-terminal extension of S100B is not part of the surface implicated in annexin VI recognition. S100 proteins permeabilize membrane bilayers similarly to annexins. Co-immunoprecipitation/binding assays, intermediate filament assembly assay, liposome permeabilization and calcium influx assay Biochimica et biophysica acta Medium 11108963
2002 Alpha1-adrenergic stimulation induces the S100B gene in cardiac myocytes specifically through the alpha1A-adrenergic receptor and the PKC signaling pathway. A basic promoter (spanning 162 bp upstream of the transcription initiation site) was identified as essential for transcription, along with positive and negative regulatory elements. TEF-1 transrepressed and RTEF-1 transactivated the maximal S100B promoter. This identifies S100B as a negative feedback regulator of alpha1-adrenergic/PKC-driven cardiac hypertrophy. Luciferase reporter assays with sequential 5'-deletion constructs, transfection of cardiac myocytes, adrenergic receptor agonists/antagonists American journal of physiology. Heart and circulatory physiology Medium 12388300
1998 Forced expression of S100B in neonatal rat cardiac myocyte cultures and high-level expression in transgenic mouse hearts inhibits cardiac hypertrophy and associated phenotype by modulating protein kinase C-dependent pathways. S100B is induced after myocardial infarction and acts as a negative feedback regulator limiting cardiomyocyte hypertrophy. Forced gene expression in primary myocyte cultures, transgenic mouse model, PKC pathway analysis Canadian journal of applied physiology Medium 9677434
2010 S100B induces apoptosis in cardiomyocytes via an extracellular mechanism by engaging RAGE and activating ERK1/2 and p53 signaling. Knocking out S100B augmented hypertrophy, decreased apoptosis, and preserved cardiac function following myocardial infarction. S100B knockout mouse model, exogenous S100B treatment, Western blot for ERK1/2 and p53 signaling Amino acids Medium 20204434
1994 Transgenic mice expressing 2-fold and 7-fold elevated S100B show concomitant astrocytosis and axonal sprouting in the hippocampus (elevated GFAP, neurofilament L, phosphorylated NF-H/M, beta-tubulin), demonstrating that elevated S100B in vivo promotes both astrocyte morphological changes and neurite proliferation, particularly in the dentate gyrus. S100B transgenic mouse model, Western blot, immunocytochemistry Proceedings of the National Academy of Sciences of the United States of America Medium 8202493
2019 Calsyntenin 3β (a novel ER protein in thermogenic adipocytes) promotes ER localization and secretion of S100B from brown adipocytes despite S100B lacking a signal peptide. S100B stimulates neurite outgrowth from sympathetic neurons in vitro. S100B deficiency phenocopies calsyntenin 3β deficiency (reduced sympathetic innervation of adipose tissue), and forced S100B expression in brown adipocytes rescues the innervation defect caused by calsyntenin 3β ablation. Genetic loss/gain-of-function in adipocytes, in vitro neurite outgrowth assay, rescue experiments with forced S100B expression Nature High 31043739
2023 YAP/TAZ in adipocytes transcriptionally repress S100B expression by competing with C/EBPβ for binding to the zinc finger-2 domain of PRDM16, thereby suppressing PRDM16-C/EBPβ-mediated S100b transcription. Adrenergic stimulation phosphorylates and inactivates YAP/TAZ, releasing this repression to allow S100B expression and sympathetic innervation of beige fat. Adipocyte-specific Yap/Taz knockout, AAV-S100B overexpression, co-immunoprecipitation of YAP/TAZ-PRDM16-C/EBPβ interactions, transcriptional reporter assays Nature communications High 37925548
2014 SOX10 transcription factor transactivates the S100B promoter in Schwann cells through three core response elements in the S100B promoter and intron 1 containing SOX motifs. SOX10 overexpression dramatically induces S100B expression; SOX10 knockdown suppresses S100B. Knockdown of either SOX10 or S100B enhances Schwann cell proliferation, and S100B knockdown impairs myelination in dorsal root ganglion co-cultures. SOX10 overexpression/shRNA knockdown, S100B shRNA knockdown, luciferase reporter with SOX motif mapping, DRG myelination assay PloS one High 25536222
2007 SOX9 and its coactivators SOX5/SOX6 (the SOX trio) transcriptionally induce S100A1 and S100B expression in chondrocytes, as shown by microarray, luciferase reporter assay, EMSA, and ChIP with identified enhancer elements. S100B overexpression suppresses hypertrophic chondrocyte differentiation and mineralization; silencing of both S100A1 and S100B stimulated terminal differentiation and reversed SOX-trio-mediated inhibition. Microarray, luciferase reporter assay, EMSA, chromatin immunoprecipitation, S100B overexpression and siRNA knockdown in chondrogenic cells EMBO reports High 17396138
1999 In replicating myoblasts, S100B localizes to Golgi membranes, vimentin intermediate filaments (IFs), and microtubule (MT) structures as shown by immunofluorescence and immunogold electron microscopy. After colchicine treatment (MT disruption), a fraction of S100B remains with collapsed vimentin IFs while another fraction follows endoplasmic membranes, indicating S100B interacts with both MT and IF networks. In fused myotubes S100B is mostly associated with vimentin IFs, suggesting a role in regulating MT and IF dynamics. Immunofluorescence, immunogold electron microscopy, colchicine treatment (functional perturbation) Cell calcium Medium 10326676
2001 S100B is expressed in microglia in a filamentous network and diffusely in the cytoplasm, and associates with intracellular membranes. During phagocytosis of opsonized Cryptococcus neoformans, S100B redistributes around phagosomes. IFN-γ treatment causes cell shape changes, S100B redistribution, and downregulation of S100B mRNA. Exogenous nanomolar-to-micromolar S100B increases IFN-γ-induced iNOS mRNA expression and NO secretion in microglia. Immunofluorescence, RT-PCR, Western blot, phagocytosis assay with live imaging, NO measurement Glia Medium 11180510
2013 S100B promotes glioma growth in vivo by chemoattracting myeloid-derived macrophages/tumor-associated macrophages (TAM). S100B expression induced RAGE in vivo, but RAGE ablation did not significantly inhibit TAM infiltration, indicating RAGE-independent mechanisms. S100B upregulated CCL2 chemokine in high-S100B tumors, and CCL2 correlated with S100B expression in human glioma datasets. Stable transfection of GL261 glioma cells (S100B overexpression and knockdown), intracranial tumor implantation, RAGE knockout mice, chemokine analysis, TCGA database correlation Clinical cancer research Medium 23719262
2013 S100B upregulates TNF-α and M1 macrophage markers in macrophages via RAGE; TNF-α reciprocally augments S100B secretion from adipocytes. Silencing S100B or RAGE neutralization significantly ameliorated TNF-α hypersecretion from macrophages stimulated with adipocyte conditioned media, establishing a paracrine loop between adipocytes (S100B secretion) and macrophages (RAGE-mediated activation). siRNA knockdown of S100B, RAGE-neutralizing antibody, conditioned media transfer, co-culture, ELISA Obesity (Silver Spring, Md.) Medium 23804363
2015 S100B upregulates IL-1β and CCL22 in macrophages (RAW264.7 and primary bone marrow-derived). In the Experimental Autoimmune Uveoretinitis model, S100B deletion in mice resulted in significantly reduced disease severity, reduced macrophage infiltration, and reduction of CCL22 and IL-1β in retinas, establishing a role for S100B in promoting macrophage-dependent retinal inflammation. PCR array, real-time PCR, flow cytometry, ELISA, S100B knockout mouse model, EAU histological grading PloS one Medium 26204512
2017 S100B impairs oligodendrocyte differentiation (OPC to mature MBP+ OL transition and morphological maturation) and myelination at micromolar concentrations. These effects were abolished by the RAGE antagonist FPS-ZM1, establishing that elevated S100B acts through the S100B-RAGE axis to impair oligodendrogenesis. In organotypic cerebellar slices, elevated S100B also impaired myelination, compromised neuronal/synaptic integrity, induced astrogliosis, NF-κB activation, and inflammation. Primary OL cultures, organotypic cerebellar slice cultures, RAGE antagonist (FPS-ZM1) rescue, immunofluorescence, Western blot Neuropharmacology Medium 29126910
2018 S100B promotes microglia M1 polarization with enhanced migration and inhibits M2 polarization. NF-κB is essential for S100B-mediated control of microglia M1/M2 polarization and migration. In vivo, S100B aggravated cerebral ischemia (MCAO model) and exacerbated microglia M1 polarization and migration. Real-time PCR, NF-κB pathway inhibition, migration assay, MCAO mouse model, S100B treatment in vivo Inflammation research Medium 30229393
2004 Strain injury to neuronal-glial co-cultures causes immediate release of S100B; adding exogenous S100B (10–100 nM) at 15 seconds, 6 hours, or 24 hours post-injury reduced delayed neuronal death at 48 hours, demonstrating a direct neuroprotective role of S100B after traumatic injury. In vitro stretch injury model (Silastic membrane), exogenous S100B treatment at multiple time points, propidium iodide neuronal death assay Journal of neurochemistry Medium 15584905
1999 S100beta-induced apoptosis in human neuronal precursor NT2/D1 cells is regulated by Bcl-2: S100beta treatment down-regulated Bcl-2 protein; bcl-2 gene transfer elevated Bcl-2 and repressed S100beta-mediated cell death; antisense bcl-2 knockdown in differentiated (retinoic acid-treated, Bcl-2-high) NT2 cells increased susceptibility to S100beta-induced apoptosis. bcl-2 gene transfer, antisense oligonucleotide knockdown, retinoic acid differentiation, cell death assays Brain research. Molecular brain research Medium 10381557
2020 Pentamidine (an S100B inhibitor) disrupts S100B-wtp53 interaction in colon cancer biopsies, reducing S100B's ability to activate RAGE/phospho-p38 MAPK/NF-κB signaling, and restores wtp53 pro-apoptotic control (reduces iNOS, VEGF, IL-6 upregulation and rescues Bax). Niosomal pentamidine delivery (PENVE) was required for tissue penetration. Human biopsy cultures, immunoblot, EMSA, ELISA, biochemical assays for S100B-wtp53 interaction and downstream signaling Journal of cellular and molecular medicine Medium 32022398
2015 S100B knockdown in melanocytes increased apoptosis through inhibition of PI3K/AKT, NF-κB, and ERK activation, suggesting intracellular S100B protects melanocytes from chemically induced cytotoxicity. No RAGE expression was detected in melanocytes and CD166/ALCAM showed no significant function in melanocyte survival, pointing to intracellular (rather than RAGE-mediated) S100B function in this cell type. S100B siRNA knockdown, Western blot for PI3K/AKT, NF-κB, ERK signaling, flow cytometry, LDH assay Experimental dermatology Medium 24451020
2015 In mesangial cells, HG-induced Steap4 protein expression was dependent on S100B; protein-protein interaction between Steap4 and S100B was confirmed by mass spectrometry of immunoprecipitated S100B. S100B-induced Steap4 gene transcription is mediated through a STAT3 site in the Steap4 promoter (via JNK, PI3K, and JAK/STAT3 pathways). Steap4 overexpression attenuates S100B-induced collagen IV, fibronectin, COX-2, and TGF-β expression. Co-immunoprecipitation/mass spectrometry, Steap4 promoter mutation analysis, kinase inhibitors (SP600125, LY294002, AG490), Steap4 overexpression, streptozotocin diabetic mouse model Journal of cellular and molecular medicine Medium 25817898

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 S100B's double life: intracellular regulator and extracellular signal. Biochimica et biophysica acta 585 19110011
2003 S100B in brain damage and neurodegeneration. Microscopy research and technique 480 12645009
2018 The S100B story: from biomarker to active factor in neural injury. Journal of neurochemistry 314 30144068
1997 S100beta induces neuronal cell death through nitric oxide release from astrocytes. Journal of neurochemistry 296 9375660
2000 Elimination of S100B and renal function after cardiac surgery. Journal of cardiothoracic and vascular anesthesia 210 11139112
2007 Structural and functional insights into RAGE activation by multimeric S100B. The EMBO journal 209 17660747
2007 S100B in neuropathologic states: the CRP of the brain? Journal of neuroscience research 202 17348038
2012 The S100B protein in biological fluids: more than a lifelong biomarker of brain distress. Journal of neurochemistry 194 22145907
2001 S100B expression in and effects on microglia. Glia 158 11180510
2007 Reliability of S100B in predicting severity of central nervous system injury. Neurocritical care 156 17522796
2019 Innervation of thermogenic adipose tissue via a calsyntenin 3β-S100b axis. Nature 154 31043739
1994 Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice. Proceedings of the National Academy of Sciences of the United States of America 154 8202493
2005 Spatial and temporal expression of S100B in cells of oligodendrocyte lineage. Glia 137 15782413
2006 S100B binding to RAGE in microglia stimulates COX-2 expression. Journal of leukocyte biology 122 17023559
2011 S100B protein in neurodegenerative disorders. Clinical chemistry and laboratory medicine 114 21303299
2002 S100B protein in biological fluids: a tool for perinatal medicine. Clinical chemistry 103 12446464
2010 The calcium-binding protein S100B down-regulates p53 and apoptosis in malignant melanoma. The Journal of biological chemistry 96 20587415
2023 The S100B Protein: A Multifaceted Pathogenic Factor More Than a Biomarker. International journal of molecular sciences 94 37298554
2013 Serum S100B represents a new biomarker for mood disorders. Current drug targets 94 23701298
2007 S100A1 and S100B, transcriptional targets of SOX trio, inhibit terminal differentiation of chondrocytes. EMBO reports 94 17396138
2018 Cellular and molecular mechanisms of sarcopenia: the S100B perspective. Journal of cachexia, sarcopenia and muscle 90 30499235
2013 S100B promotes glioma growth through chemoattraction of myeloid-derived macrophages. Clinical cancer research : an official journal of the American Association for Cancer Research 86 23719262
2013 S100B protein in tissue development, repair and regeneration. World journal of biological chemistry 80 23580916
2011 Usefulness of S100B protein in neurological disorders. JPMA. The Journal of the Pakistan Medical Association 79 21465945
2002 Circulating S100beta protein is increased in intrauterine growth-retarded fetuses. Pediatric research 78 11809917
2011 S100B and APP promote a gliocentric shift and impaired neurogenesis in Down syndrome neural progenitors. PloS one 77 21779383
2009 Characterization of RAGE, HMGB1, and S100beta in inflammation-induced preterm birth and fetal tissue injury. The American journal of pathology 74 19679874
2004 Relationship between S100beta and GFAP expression in astrocytes during infarction and glial scar formation after mild transient ischemia. Brain research 73 15328028
2023 S100B, Actor and Biomarker of Mild Traumatic Brain Injury. International journal of molecular sciences 71 37047574
1998 Cerebral emboli and serum S100beta during cardiac operations. The Annals of thoracic surgery 70 9647074
2004 S100B in schizophrenic psychosis. International review of neurobiology 69 15006498
1997 GFAP and S100beta expression in the cortex and hippocampus in response to mild cortical contusion. Journal of neurotrauma 60 9383091
2005 SNPs and haplotypes in the S100B gene reveal association with schizophrenia. Biochemical and biophysical research communications 59 15670788
2008 S100B is expressed in, and released from, OLN-93 oligodendrocytes: Influence of serum and glucose deprivation. Neuroscience 58 18472341
2018 The neuronal S100B protein is a calcium-tuned suppressor of amyloid-β aggregation. Science advances 57 29963623
1997 S100A1 and S100B expression and target proteins in type I diabetes. Endocrinology 54 9389498
2010 The Calcium-Dependent Interaction of S100B with Its Protein Targets. Cardiovascular psychiatry and neurology 51 20827422
2013 The role of S100B in the interaction between adipocytes and macrophages. Obesity (Silver Spring, Md.) 50 23804363
2004 Cerebral and extracerebral release of protein S100B in cardiac surgical patients. Anaesthesia 49 15023104
2004 S100B protein is released by in vitro trauma and reduces delayed neuronal injury. Journal of neurochemistry 48 15584905
1996 Identification of an S100A1/S100B target protein: phosphoglucomutase. Cell calcium 48 8894274
2017 S100B expression in breast cancer as a predictive marker for cancer metastasis. International journal of oncology 46 29345293
2013 S100B and schizophrenia. Psychiatry and clinical neurosciences 46 23438158
2007 S100B content and secretion decrease in astrocytes cultured in high-glucose medium. Neurochemistry international 46 17350141
2018 S100B promotes microglia M1 polarization and migration to aggravate cerebral ischemia. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 45 30229393
2015 S100B and ADMA in cerebral small vessel disease and cognitive dysfunction. Journal of the neurological sciences 45 25990800
2014 SOX10 transactivates S100B to suppress Schwann cell proliferation and to promote myelination. PloS one 45 25536222
2013 The evolution of S100B inhibitors for the treatment of malignant melanoma. Future medicinal chemistry 45 23256816
2018 S100B immunization triggers NFκB and complement activation in an autoimmune glaucoma model. Scientific reports 42 29959432
2011 S100B transgenic mice develop features of Parkinson's disease. Archives of medical research 42 21376255
2017 Impaired oligodendrogenesis and myelination by elevated S100B levels during neurodevelopment. Neuropharmacology 39 29126910
2005 The ischemic rat heart releases S100B. Life sciences 38 15921704
2022 Neuron Specific Enolase, S100-beta protein and progranulin as diagnostic biomarkers of status epilepticus. Journal of neurology 37 35190890
2016 Higher Plasma S100B Concentrations in Schizophrenia Patients, and Dependently Associated with Inflammatory Markers. Scientific reports 36 27279465
2021 Alarmins (IL-33, sST2, HMGB1, and S100B) as potential biomarkers for schizophrenia. Journal of psychiatric research 34 33957300
2003 S100B testing in pregnancy. Clinica chimica acta; international journal of clinical chemistry 34 12927678
2015 S100B Up-Regulates Macrophage Production of IL1β and CCL22 and Influences Severity of Retinal Inflammation. PloS one 31 26204512
2003 Human milk contains S100B protein. Biochimica et biophysica acta 31 12527118
2020 Pentamidine niosomes thwart S100B effects in human colon carcinoma biopsies favouring wtp53 rescue. Journal of cellular and molecular medicine 30 32022398
2010 Risk variants in the S100B gene predict elevated S100B serum concentrations in healthy individuals. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 30 19330775
1999 Replicating myoblasts and fused myotubes express the calcium-regulated proteins S100A1 and S100B. Cell calcium 30 10326676
2014 S100B blood levels and childhood trauma in adolescent inpatients. Journal of psychiatric research 29 25669696
2000 S100A1 and S100B interactions with annexins. Biochimica et biophysica acta 29 11108963
2012 S100B protein as a possible participant in the brain metastasis of NSCLC. Medical oncology (Northwood, London, England) 28 22286962
2006 Raised serum S100B protein levels in neuropsychiatric lupus. Annals of the rheumatic diseases 28 16699054
2021 Correlation between S100B and severity of depression in MDD: A meta-analysis. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 27 34854356
2013 Clinical use of the calcium-binding S100B protein. Methods in molecular biology (Clifton, N.J.) 27 23296623
2002 Regulation of the S100B gene by alpha 1-adrenergic stimulation in cardiac myocytes. American journal of physiology. Heart and circulatory physiology 27 12388300
2016 Serum S100B Protein is Specifically Related to White Matter Changes in Schizophrenia. Frontiers in cellular neuroscience 26 27013967
2016 S100B and S100B autoantibody as biomarkers for early detection of brain metastases in lung cancer. Translational lung cancer research 26 27652205
2020 Tau, S100B and NSE as Blood Biomarkers in Acute Cerebrovascular Events. In vivo (Athens, Greece) 24 32871787
2014 S100A1 and S100B expression patterns identify differentiation status of human articular chondrocytes. Journal of cellular physiology 24 24402969
2017 S100A1 and S100B: Calcium Sensors at the Cross-Roads of Multiple Chondrogenic Pathways. Journal of cellular physiology 23 27925190
2003 Expression of S100A2 and S100B proteins in epithelial tumors of the skin. Journal of cutaneous pathology 23 12834486
1999 Bcl-2 expression regulates cell sensitivity to S100beta-mediated apoptosis. Brain research. Molecular brain research 23 10381557
2018 Does S100B have a potential role in affective disorders? A literature review. Nordic journal of psychiatry 22 29764272
2013 S100B as a glial cell marker in diabetic peripheral neuropathy. Neuroscience letters 22 24211224
2013 S100B protein in serum is elevated after global cerebral ischemic injury. World journal of emergency medicine 22 25215112
2010 S100B: a multifunctional role in cardiovascular pathophysiology. Amino acids 22 20204434
2020 S100B protein: general characteristics and pathophysiological implications in the Central Nervous System. The International journal of neuroscience 21 32772615
2017 Evaluation of dietary and lifestyle changes as modifiers of S100β levels in Alzheimer's disease. Nutritional neuroscience 21 28696163
2015 Differential temporal expression of S100β in developing rat brain. Frontiers in cellular neuroscience 21 25852479
2006 Plasma S100beta and NSE levels and progression in multiple sclerosis. Journal of the neurological sciences 21 17187827
2003 S100B and cardiac surgery: possibilities and limitations. Restorative neurology and neuroscience 21 14530577
2021 S100B Protein as a Therapeutic Target in Multiple Sclerosis: The S100B Inhibitor Arundic Acid Protects from Chronic Experimental Autoimmune Encephalomyelitis. International journal of molecular sciences 20 34948360
2018 Elevated Plasma S100B, Psychotic Symptoms, and Cognition in Schizophrenia. The Psychiatric quarterly 20 28435992
2015 Polymorphisms in DCDC2 and S100B associate with developmental dyslexia. Journal of human genetics 20 25877001
2011 S100B proteins in febrile seizures. Seizure 20 22130006
1998 Induction of S100b in myocardium: an intrinsic inhibitor of cardiac hypertrophy. Canadian journal of applied physiology = Revue canadienne de physiologie appliquee 20 9677434
2017 S100β as a serum marker in endocrine resistant breast cancer. BMC medicine 19 28399921
2015 Normal cerebellar development in S100B-deficient mice. Cerebellum (London, England) 19 25342137
2014 S100B as a potential biomarker for the detection of cytotoxicity of melanocytes. Experimental dermatology 19 24451020
2003 Carotid endarterectomy and gliofibrillar S100b protein release. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 19 14716532
2011 Reference values for venous and capillary S100B in children. Clinica chimica acta; international journal of clinical chemistry 18 21864523
2004 Over-expression of S100B protein in children with cerebral palsy or delayed development. Brain & development 18 15030908
2023 Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis. Nature communications 17 37925548
2021 New insights into the role and origin of pituitary S100β-positive cells. Cell and tissue research 17 34550453
2020 S100B as a new fecal biomarker of inflammatory bowel diseases. European review for medical and pharmacological sciences 17 31957846
2015 The clinical and diagnostic utility of S100B in preterm newborns. Clinica chimica acta; international journal of clinical chemistry 17 25704302
2015 Steap4 attenuates high glucose and S100B-induced effects in mesangial cells. Journal of cellular and molecular medicine 17 25817898

Missed literature

Know a paper Affinage missed for S100B? Flag it for the maintainers and the community.

No submissions yet.