Affinage

SOX5

Transcription factor SOX-5 · UniProt P35711

Length
763 aa
Mass
84.0 kDa
Annotated
2026-04-28
100 papers in source corpus 41 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOX5 is an SRY-related HMG-box transcription factor that functions as a context-dependent transcriptional cofactor across chondrogenesis, immune differentiation, neural development, and cancer. In cartilage, the long isoform (L-Sox5) homodimerizes or heterodimerizes with Sox6 via a coiled-coil domain, binding paired HMG sites on enhancers of cartilage matrix genes (Col2a1, Agc1, COMP, Matn1, miR-140) to potentiate Sox9-driven transcription at super-enhancers genome-wide; Sox5/Sox6 double-knockout mice exhibit severe chondrodysplasia, failed joint morphogenesis, and notochord defects (PMID:9755172, PMID:18559420, PMID:26150426, PMID:11680692, PMID:12571105). In Th17 cells, a lineage-specific isoform (Sox5t) physically interacts with c-Maf and activates a distal RORγt enhancer (RORCE2), enabling STAT3 recruitment and chromatin looping to the RORγt promoter to drive Th17 differentiation (PMID:25073789, PMID:33473108). SOX5 can also repress SoxE-dependent transcription by recruiting CtBP2 and HDAC1 corepressors, as demonstrated in the melanocyte lineage where it inhibits Sox10 target genes, and it functions as a direct transcriptional activator of Twist1, EZH2, MMP-9, and VEGF in cancer contexts to promote epithelial–mesenchymal transition, invasion, and angiogenesis (PMID:18703590, PMID:24607904, PMID:30854049, PMID:29706965).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 High

    Establishing the DNA-binding specificity and structural mode of Sox5: its HMG box binds the minor groove of AACAAT with nanomolar affinity and induces DNA bending, defining Sox5 as a canonical HMG-box transcription factor.

    Evidence In vitro footprinting, EMSA, CD, and 2D NMR on purified mouse Sox5 HMG box

    PMID:8078768

    Open questions at the time
    • Full-length protein binding properties unknown
    • No cellular target genes identified
    • In vivo relevance of AACAAT binding not tested
  2. 1998 High

    Revealing how L-Sox5 achieves cooperative enhancer occupancy: its coiled-coil domain mediates homo- and heterodimerization with Sox6, enabling efficient binding to paired HMG sites and cooperative activation of the Col2a1 chondrocyte enhancer with Sox9.

    Evidence Dimerization assays, DNA-binding assays, and reporter assays in 10T1/2 and MC615 cells; biophysical characterization of HMG box unfolding by DSC and NMR

    PMID:9710541 PMID:9755172

    Open questions at the time
    • Genome-wide binding landscape unknown
    • Structural basis of the Sox5–Sox6 coiled-coil interface unresolved
    • Whether dimerization is required in vivo not tested
  3. 2001 High

    Genetic proof that Sox5 and Sox6 are essential, largely redundant regulators of chondrogenesis: double-null mice show catastrophic failure of chondroblast differentiation and skeletal formation, while single knockouts are viable.

    Evidence Sox5−/−/Sox6−/− double-knockout mouse embryos with in vivo skeletal analysis; NMR solution structure of free Sox5 HMG box confirmed L-shaped fold

    PMID:11266597 PMID:11680692

    Open questions at the time
    • Downstream transcriptional targets not identified genome-wide
    • Relative contribution of each gene in specific skeletal elements unclear
    • Whether Sox5 has Sox6-independent roles not addressed
  4. 2002 High

    Establishing the transcriptional hierarchy: Sox9 is required upstream of Sox5/Sox6 expression, meaning Sox5/Sox6 act as Sox9-induced cofactors rather than independent initiators of chondrogenesis.

    Evidence Conditional Sox9 inactivation before mesenchymal condensation abolishes Sox5/Sox6 expression (Cre/loxP, in situ hybridization)

    PMID:12414734

    Open questions at the time
    • Whether Sox9 directly activates Sox5 transcription or acts indirectly unknown
    • Feedback from Sox5/Sox6 onto Sox9 not tested
  5. 2003 High

    Expanding Sox5/Sox6 function beyond cartilage: they are essential for notochord ECM sheath formation and nucleus pulposus development, with double knockouts lacking expression of Col2a1, aggrecan, and perlecan in notochord cells.

    Evidence Sox5−/−/Sox6−/− mice analyzed by in situ hybridization, immunohistochemistry, and apoptosis assays in notochord

    PMID:12571105

    Open questions at the time
    • Mechanism of notochord cell death (apoptosis vs. anoikis) unclear
    • Direct promoter occupancy in notochord not demonstrated
  6. 2008 High

    Defining the enhancer-level mechanism: L-Sox5/Sox6 bind specific elements in the Agc1 far-upstream enhancer to cooperatively increase Sox9 binding efficiency, and Sox5 recruits the corepressors CtBP2 and HDAC1 on Sox10 target genes in melanocytes, establishing Sox5 as a dual-function cofactor (coactivator or corepressor depending on context).

    Evidence ChIP, EMSA, transgenic reporter assays for Agc1 enhancer; genetic epistasis (Sox5 KO × Sox10 het), ChIP for CtBP2/HDAC1 recruitment, and reporter assays for melanocyte genes; Tip60 interaction with Sox5/Sox9 on Col2a1 enhancer by yeast two-hybrid and Co-IP

    PMID:18390577 PMID:18559420 PMID:18703590

    Open questions at the time
    • Structural basis for cofactor switching unknown
    • Whether CtBP2/HDAC1 recruitment occurs genome-wide or at select loci not determined
    • How Sox5 discriminates between coactivator and corepressor modes unresolved
  7. 2010 High

    Broadening Sox5 roles to sperm motility, neural development, and joint morphogenesis: S-Sox5 directly activates the SPAG6 promoter; Sox5 modulates WNT-β-catenin signaling in neural progenitors to control cell cycle exit; and Sox5/Sox6 are required for synovial joint interzone formation.

    Evidence ChIP/EMSA/site mutagenesis for SPAG6 promoter; in ovo overexpression/knockdown with WNT reporter in chick; Col2Cre and Gdf5Cre conditional double-KO mice for joint phenotype

    PMID:20206616 PMID:20448664 PMID:20668334

    Open questions at the time
    • Whether S-Sox5 has distinct target repertoire from L-Sox5 is unknown
    • Direct Sox5 targets in neural progenitors not identified
    • How Sox5/Sox6 regulate interzone specification molecularly unclear
  8. 2014 High

    Identifying Sox5 as a key immune transcription factor: a Th17-specific isoform (Sox5t) interacts with c-Maf via the HMG domain and cooperatively activates the RORγt promoter downstream of STAT3, establishing Sox5 as essential for Th17 differentiation and autoimmune pathology.

    Evidence Co-IP with domain mapping, ChIP on RORγt promoter, T cell-specific Sox5 KO mice in EAE model, epistasis with Stat3-deficient and RORγt-deficient cells

    PMID:25073789

    Open questions at the time
    • Genome-wide Sox5t targets in Th17 cells unknown
    • Whether Sox5t has unique structural features vs. L-Sox5 not determined
    • Role in human Th17-driven diseases not directly demonstrated
  9. 2014 High

    Sox5 acts as a cofactor for BMP R-Smads: it physically interacts with Smad1/4 and is required for their recruitment to BMP regulatory elements, activating BMP target genes for neural crest and epidermal patterning in Xenopus.

    Evidence Co-IP of Sox5 with BMP R-Smads, ChIP for Smad1/4 at BMP response elements, loss-of-function patterning phenotype in Xenopus embryos

    PMID:25453832

    Open questions at the time
    • Conservation of Sox5–Smad interaction in mammals not tested
    • Whether this applies to all BMP targets or a subset unclear
  10. 2015 High

    Genome-wide mapping reveals SOX9 and SOX5/SOX6 co-occupy thousands of sites including nearly all cartilage super-enhancers, with SOX6 preferring tandem SOX motifs and SOX9 inverted motifs, defining the chromatin logic of chondrocyte identity.

    Evidence ChIP-seq for SOX6 and SOX9 in RCS cells, motif enrichment analysis, super-enhancer identification

    PMID:26150426

    Open questions at the time
    • SOX5-specific ChIP-seq not performed (SOX6 used as proxy)
    • 3D chromatin architecture at these super-enhancers not mapped in chondrocytes
    • Functional hierarchy among co-occupied enhancers unclear
  11. 2017 Medium

    Multiple studies establish Sox5 as a direct transcriptional activator in cancer and metabolic contexts: Sox5 binds the Twist1 promoter to drive EMT in breast and prostate cancer, activates MMP-9 in rheumatoid synoviocytes, and maintains β-cell identity and insulin secretion.

    Evidence ChIP and reporter assays for Twist1 and MMP-9 promoters; Sox5 knockdown/overexpression in pancreatic islets with Ca2+ imaging and exocytosis measurements; xenograft and CIA mouse models

    PMID:24607904 PMID:28585545 PMID:29123266 PMID:29706965

    Open questions at the time
    • Direct Sox5 targets in β-cells not mapped genome-wide
    • Whether EMT-driving function is isoform-specific unknown
    • Mechanism of Sox5-mediated insulin exocytosis regulation unclear
  12. 2021 High

    The 3D chromatin mechanism of Sox5 in Th17 cells is elucidated: Sox5 binds a novel RORγt enhancer (RORCE2) to enable its looping to the RORγt promoter and STAT3 recruitment; CRISPR deletion of RORCE2 suppresses Th17 differentiation and ameliorates EAE.

    Evidence CRISPR knockout of RORCE2, 3C/chromatin looping assays, ChIP for SOX5 and STAT3, EAE model

    PMID:33473108

    Open questions at the time
    • Whether Sox5 establishes or maintains the loop is unknown
    • Other Sox5-dependent enhancer loops in Th17 cells not identified
    • RORCE2 conservation across species not established
  13. 2023 High

    SOX5 is identified as a driver of cellular rejuvenation: it binds and activates the HMGB2 enhancer (increasing H3K27ac and H3K4me1), and SOX5 gene therapy rejuvenates aged cartilage and alleviates osteoarthritis in mice.

    Evidence Genome-wide CRISPRa screen, epigenomic profiling (H3K27ac/H3K4me1 ChIP), SOX5 binding analysis, lentiviral gene therapy in aged mice

    PMID:37832549

    Open questions at the time
    • Whether SOX5-mediated rejuvenation extends beyond cartilage unknown
    • Mechanism by which HMGB2 mediates rejuvenation incompletely defined
    • Long-term safety and durability of SOX5 gene therapy not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for Sox5 isoform-specific partner selection (Sox6/c-Maf/Smad1/YAP1), the genome-wide Sox5 (as opposed to Sox6) cistrome in chondrocytes and Th17 cells, and how Sox5 switches between coactivator and corepressor modes across lineages.
  • No Sox5-specific ChIP-seq in primary chondrocytes
  • Structural model of Sox5 coiled-coil dimer interface lacking
  • Mechanism governing coactivator-to-corepressor switch unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 10 R-HSA-1266738 Developmental Biology 7 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2
Partners
CTBP2HDAC1KAT5MAFSMAD1SOX6SOX9YAP1
Complex memberships
L-Sox5/Sox6 homodimer/heterodimerSox5/Sox6/Sox9 chondrogenic trio

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Sox5 protein localizes to the nucleus of post-meiotic round spermatids in mouse testis and binds specifically to the sequence AACAAT with moderately high affinity (Kd ~10^-9 M), inducing a significant bend in the DNA characteristic of HMG box proteins. Indirect immunofluorescence, in vitro footprinting, gel retardation assays, circular dichroism spectroscopy, 2D NMR Nucleic acids research High 8078768
1998 L-Sox5 (long form of Sox5) contains a coiled-coil domain that mediates homodimerization and heterodimerization with Sox6; dimerization greatly increases efficiency of binding to DNA containing adjacent HMG sites. L-Sox5, Sox6, and Sox9 cooperatively activate Col2a1 expression through a 48 bp chondrocyte-specific enhancer containing HMG-like sites. Coiled-coil domain analysis, dimerization assays, DNA binding assays, reporter assays in 10T1/2 and MC615 cells, co-expression studies in mouse embryos The EMBO journal High 9755172
1998 The Sox5 HMG box from mouse undergoes two-stage reversible unfolding corresponding to two structural sub-domains (minor wing: helix 3 + N-terminal strand; major wing: helices I and II), with the minor wing considerably unfolded at physiological temperature (37°C). Differential scanning calorimetry, fluorescence spectroscopy, NMR Journal of molecular biology High 9710541
1999 The Sox5 HMG box binds its AACAAT target DNA with an association constant of ~4×10^7 M^-1 (ΔG = −40 to −48 kJ/mol), with binding thermodynamics characteristic of minor groove HMG box proteins including a large negative heat capacity change (~−2 kJ/K/mol) reflecting dehydration of the protein-DNA interface. Fluorescence titration, isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC) Journal of molecular biology High 10588902
2001 Sox5 (L-Sox5) and Sox6 are required for formation of cartilage in mouse embryos; double-null mutants (Sox5−/−/Sox6−/−) show severe skeletal malformations with failure of chondroblast differentiation, establishing Sox5 and Sox6 as redundant transcriptional regulators of chondrogenesis. Genetic knockout mouse models, in vivo skeletal analysis Osteoarthritis and cartilage High 11680692
2001 NMR solution structure of the mouse Sox5 HMG box in free solution reveals a characteristic twisted L-shape with two wings (major wing: helices 1 and 2; minor wing: helix 3 with N-terminal segment), with significant backbone mobility in the minor wing that increases toward termini. Multidimensional NMR with 15N-labeled protein, 15N relaxation measurements Protein science High 11266597
2002 Sox9 is required upstream of Sox5 and Sox6 in chondrogenesis; conditional inactivation of Sox9 before mesenchymal condensations abolishes Sox5 and Sox6 expression, placing Sox9 upstream of Sox5/Sox6 in the chondrogenic transcriptional hierarchy. Cre/loxP conditional knockout in mouse embryos, in situ hybridization for Sox5/Sox6 expression Genes & development High 12414734
2003 Sox5 and Sox6 are required in the notochord for formation of the extracellular matrix sheath, notochord cell survival, and development of the nucleus pulposus; Sox5−/−/Sox6−/− mice lack notochord ECM sheath and downregulate Col2a1, aggrecan, and perlecan in notochord cells. Genetic double-knockout mouse model, in situ hybridization, immunohistochemistry, apoptosis assays Development (Cambridge, England) High 12571105
2004 The combination of SOX5, SOX6, and SOX9 (the SOX trio) is sufficient to induce chondrocyte differentiation in non-chondrogenic cell types including dermal fibroblasts, suppressing hypertrophic and osteogenic differentiation simultaneously. Embryonic stem cell reporter assay, primary mesenchymal stem cell differentiation, marker gene expression, proteoglycan matrix accumulation Arthritis and rheumatism High 15529345
2007 Sox5 and Sox6, together with Sox9 and coactivators CBP/p300, activate transcription of the COMP (cartilage oligomeric matrix protein) gene; Sox9 binds directly to a 13-nucleotide element in the COMP promoter PRE, and Sox5/Sox6 cooperate with Sox9 and CBP/p300 for full activation. Reporter assays, gel shift assays, siRNA knockdown, EMSA Frontiers in bioscience Medium 17485346
2008 L-Sox5 and Sox6 drive aggrecan (Agc1) gene expression by binding to three elements in a far-upstream enhancer, which cooperatively increases the efficiency of Sox9 binding to its own recognition site within the same enhancer, thereby potentiating Sox9-driven transcription. Transgenic mouse reporter assays, ChIP, EMSA, mutational analysis of enhancer elements Molecular and cellular biology High 18559420
2008 The coactivator Tip60 physically associates with Sox9 and Sox5 (identified by yeast two-hybrid and confirmed by co-IP), and the Sox9-Tip60-DNA complex assembles on the Col2a1 enhancer; Tip60 enhances Sox9 transcriptional activity and acetylates Sox9 at K61, K253, and K398 residues. Yeast two-hybrid, Co-IP, gel shift assay, reporter assay, ChIP, subnuclear colocalization, siRNA knockdown in micromass cultures Nucleic acids research High 18390577
2008 Sox5 modulates Sox10 activity in the melanocyte lineage by binding to regulatory regions of melanocytic Sox10 target genes and recruiting corepressors CtBP2 and HDAC1, directly inhibiting Sox10-dependent promoter activation; Sox5 loss partially rescues the melanoblast reduction in Sox10 heterozygous mice. Genetic mouse models (Sox5 KO, Sox10 het crosses), ChIP showing Sox5 recruitment of CtBP2 and HDAC1, reporter assays Nucleic acids research High 18703590
2010 S-SOX5 (48-kDa short isoform) directly binds to and activates the SPAG6 (sperm-associated antigen 6) promoter via SOX5 binding sites, cooperating with FOXJ1 to stimulate SPAG6 expression; mutation of SOX5 binding sites abrogates promoter activation. Luciferase reporter assay with SOX5 binding site mutations, ChIP, EMSA, siRNA knockdown, SOX5 overexpression The Journal of biological chemistry High 20668334
2010 SOX5 overexpression in chick neural progenitors causes premature cell cycle exit, while SOX5 knockdown extends the proliferative period and causes cell death in a dorsal interneuron population; SOX5 reduces WNT-beta-catenin signaling by triggering expression of the negative regulator Axin2. In ovo overexpression and knockdown, cell cycle analysis, reporter assay for WNT pathway activity EMBO reports Medium 20448664
2010 Sox5 and Sox6 are required for proper synovial joint morphogenesis; complete Sox5/Sox6 double KO prevents joint interzone formation and cavitation, while chondrocyte-specific inactivation (Col2Cre) also blocks joint morphogenesis, establishing that Sox5/Sox6 chondrogenic function is essential for joint development. Complete and cell-type-specific conditional knockout using Cre/loxP (Sox5fl/fl6fl/fl with Col2Cre and Gdf5Cre drivers), histology, marker gene expression Developmental biology High 20206616
2010 L-Sox5/Sox6 and Nfib proteins bind to conserved proximal elements in the Matn1 (matrilin-1) promoter and modulate Sox9 transactivation in a protein dose-dependent manner to restrict expression to specific growth plate zones. Transgenic mouse reporter assays, EMSA, mutational analysis, protein binding assays Molecular and cellular biology Medium 21173167
2011 SOX5 and SOX6 physically interact with SHOX (short stature homeobox gene) via the SHOX homeodomain and SOX6 HMG domain (confirmed by yeast two-hybrid and co-immunoprecipitation in human cells), and this interaction is required for cooperative activation of the aggrecan (Agc1) upstream enhancer; LWD-causing SHOX missense mutations disrupt this interaction. Yeast two-hybrid screen, Co-IP in human cells, immunohistochemistry in human fetal growth plates, reporter assays, domain mapping Human molecular genetics High 21262861
2011 Sox5 knockout mice exhibit abnormal lung development with a delay in maturation before the saccular stage (as early as E16.5) associated with decreased fibronectin expression, an ECM component critical for branching morphogenesis. Sox5−/− mouse histology and gene expression analysis American journal of respiratory and critical care medicine Medium 21330457
2012 L-Sox5 and Sox6 enhance Sox9 homodimer-driven transcription of miR-140 by binding to an L-Sox5/Sox6/Sox9 response element in the pri-miR-140 proximal promoter, boosting Sox9's DNA-binding and/or transactivation ability as a homodimer. Reporter assays in vivo and in vitro, ChIP, DNA binding analysis with genetically modified mice The Journal of biological chemistry Medium 22547066
2014 Sox5 (novel Th17-specific isoform Sox5t) physically associates with c-Maf via the HMG domain of Sox5 and the DNA-binding domain of c-Maf; Sox5 and c-Maf cooperatively and directly activate the RORγt promoter in CD4+ T cells, acting as downstream targets of Stat3 and upstream inducers of RORγt to drive Th17 differentiation. Co-immunoprecipitation (domain mapping), ChIP on RORγt promoter, retroviral overexpression in Stat3-deficient and RORγt-deficient cells, T cell-specific Sox5 KO mice with EAE model The Journal of experimental medicine High 25073789
2014 Sox5 directly transactivates Twist1 expression in breast cancer cells by binding to the Twist1 promoter (shown by ChIP); Sox5 depletion downregulates Twist1, reduces EMT markers (N-cadherin, Vimentin, Fibronectin 1), and upregulates E-cadherin. ChIP assay, luciferase reporter, siRNA knockdown, Western blot Biochemical and biophysical research communications Medium 24607904
2014 Sox5 functions as a DNA-binding cofactor for BMP R-Smads (Smad1/4) in Xenopus ectoderm; Sox5 physically interacts with BMP R-Smads and is essential for recruitment of Smad1/4 to BMP regulatory elements, thereby activating BMP target genes required for neural crest and epidermal patterning. Xenopus embryo overexpression/knockdown, Co-IP of Sox5 with BMP R-Smads, ChIP showing Smad1/4 recruitment to BMP regulatory elements, target gene expression analysis Developmental cell High 25453832
2015 SOX9 and SOX5/SOX6 bind thousands of genomic sites genome-wide in chondrocytes, frequently co-occupying super-enhancers (SEs); SOX9 recognizes pairs of inverted SOX motifs while SOX6 favors pairs of tandem SOX motifs; together they co-activate nearly all cartilage-specific SEs to drive the chondrocyte differentiation program. Genome-wide ChIP-seq for SOX6 and SOX9 in RCS cells, motif analysis, SE analysis, in vivo validation of target gene expression Nucleic acids research High 26150426
2015 Sox5 and Sox6 transcription factors directly promote oligodendrocyte progenitor migration by activating PDGFRα expression, thereby maintaining responsiveness to PDGF-A as a migratory cue; they also cooperate with Sox9 and Sox10 to activate PDGFRα expression, in contrast to their antagonism of SoxE proteins on myelin genes. CNS-specific conditional Sox5/Sox6 double KO mice, migration assays, marker gene expression, functional rescue Glia Medium 26345464
2016 SOX5 directly binds and activates the RANKL promoter in IL-6-stimulated rheumatoid synovial fibroblasts; ChIP shows ~3-fold enrichment of RANKL-specific DNA in anti-SOX5 immunoprecipitate after IL-6 treatment; knockdown of SOX5 reduces IL-6-mediated RANKL upregulation and bone erosion in CIA mice. ChIP, overexpression/knockdown studies, in vivo CIA mouse model with local SOX5 silencing, immunohistochemistry Scientific reports Medium 27550416
2017 Sox5 promotes EMT and prostate cancer metastasis as a master regulator of TGF-β-induced EMT; Smad3 binds to the Sox5 promoter and regulates its expression, and Sox5 in turn binds to the Twist1 promoter to activate Twist1, which initiates EMT. ChIP, luciferase reporter assay, siRNA knockdown, xenograft mouse model, Western blot British journal of cancer Medium 29123266
2017 SOX5 promotes migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis by directly binding to and activating the MMP-9 promoter; ChIP confirms SOX5 binding to MMP-9 promoter and deletion of the SOX5 binding site abolishes promoter-driven transcription; SOX5 knockdown reduces MMP-9 expression and pannus invasion in CIA mice. ChIP, luciferase reporter with SOX5 binding site deletion, transwell assay, in vivo CIA mouse model Frontiers in immunology High 29706965
2017 Sox5 regulates beta-cell phenotype and insulin secretion; Sox5 knockdown reduces depolarization-evoked Ca2+-influx and β-cell exocytosis, while SOX5 overexpression reverses expression perturbations in a T2D mouse model and improves glucose-stimulated insulin secretion in human islets. Sox5 knockdown/overexpression in pancreatic islets, Ca2+ imaging, patch-clamp exocytosis measurements, gene expression profiling Nature communications High 28585545
2017 Sox5 can suppress PDGFB-induced glioma development in Ink4a-deficient cells by increasing p27(Kip1) levels and inducing cellular senescence; Sox5 overexpression reduces Akt activation and increases p27(Kip1), and inhibition of p27(Kip1) reverses Sox5-mediated effects on proliferation and senescence. Retroviral overexpression of Sox5 in primary brain cell cultures, glioma mouse model, Western blot for Akt and p27(Kip1), p27 inhibition rescue experiments Oncogene Medium 19219070
2017 SOX5, SOX6, and SOX21 prevent oncogene-driven transformation of brain stem cells; elevated SOX5/6/21 promotes cell cycle exit upon oncogenic stress and prevents glioma-like tumor formation; restoring SOX5/6/21 in glioblastoma cells enables CDK inhibitor expression, decreases p53 protein turnover, and triggers cellular senescence and apoptosis. Genetic ablation (Sox5/6/21 triple KO), in vivo mouse brain tumor model, overexpression in human glioblastoma cells, cell cycle analysis Cancer research Medium 28687615
2018 SOX5 promotes breast cancer proliferation and invasion by directly binding to and transactivating the EZH2 promoter; ChIP-seq and quantitative ChIP confirm SOX5 binding, and the biological effect of SOX5 is dependent on EZH2 expression. ChIP-seq, quantitative ChIP, luciferase reporter assay, gain/loss-of-function studies with MTT, colony formation, invasion assays Oncology letters Medium 30854049
2018 SOX5 interacts with YAP1 as a protein complex in NSCLC cells to drive malignant potential; SOX5 is preferentially expressed by cancer stem-like cells, and silencing YAP1 attenuates malignant processes consistent with SOX5 loss; SOX5 overexpression reverses YAP1 knockdown-mediated effects. Co-immunoprecipitation, gain/loss-of-function studies, xenograft model American journal of cancer research Medium 29888108
2019 SOX5 directly activates the GLUT4 promoter and is regulated by the VEGFR2/AKT1/GSK3β signaling pathway in ovarian cancer cells; SOX5 overexpression rescues GLUT4 expression and glycolysis suppressed by apatinib. Dual-luciferase reporter assay for GLUT4 promoter, RNA-seq, Western blot, xenograft model Cellular oncology Medium 31325096
2019 FOX-A1 directly binds to the SOX5 promoter and transactivates SOX5 expression in lung adenocarcinoma, as demonstrated by ChIP-seq and ChIP assays; SOX5 is a downstream target of FOX-A1 driving EMT and chemoresistance. ChIP-seq, ChIP assay, qRT-PCR, Western blot, knockdown studies EBioMedicine Medium 31147293
2019 SOX5 induces angiogenesis in lung adenocarcinoma by activating STAT3 phosphorylation and increasing VEGF expression; SOX5 overexpression promotes tube formation capacity of endothelial cells, and this is dependent on STAT3/VEGF signaling. Tube formation assay, lentiviral overexpression/knockdown, qRT-PCR, Western blot, tissue microarray OncoTargets and therapy Low 30254466
2020 Brachyury directly binds to two motifs in the SOX5 promoter (one canonical and one novel Bry-binding motif) and activates SOX5 transcription; SOX5 is a direct downstream target of Brachyury and mediates Brachyury-driven EMT and breast cancer bone metastasis. ChIP assay, luciferase reporter assay with binding motif identification, in vitro and in vivo metastasis assays Carcinogenesis Medium 31713604
2020 SOX5 transcriptionally activates VEGF expression to promote neuroprotection; SOX5 overexpression rescues LPS-induced apoptosis in PC-12 cells via VEGF-dependent PI3K/AKT pathway activation, as confirmed by ChIP-PCR and dual luciferase reporter assay. ChIP-PCR, dual luciferase reporter assay, Western blot, TUNEL assay, CCK-8 assay Gene Low 32949698
2021 SOX5 activates a novel RORγt enhancer (RORCE2) in Th17 cells by binding to its SOX5 binding site, which enables RORCE2 looping to the RORγt promoter and recruitment of STAT3 to the RORγt locus; RORCE2 deficiency suppresses RORγt expression and Th17 differentiation. CRISPR knockout of RORCE2, chromatin conformation capture (3C/looping assay), ChIP showing SOX5 and STAT3 binding, Th17 differentiation assays, EAE mouse model Nature communications High 33473108
2021 TNF-α upregulates SOX5 expression in human bone marrow mesenchymal stem cells, and SOX5 inhibits osteogenic differentiation through the KLF4 signaling pathway; SOX5 overexpression increases KLF4 expression, and KLF4 knockdown abrogates the inhibitory effect of SOX5 on osteogenesis. Overexpression/knockdown (RNA interference), ALP activity assay, RT-qPCR, Western blot, epistasis by KLF4 knockdown rescue Molecules and cells Medium 29890823
2023 SOX5 overexpression acts as a driver of cellular rejuvenation by binding to and elevating enhancer activity (H3K27ac and H3K4me1) of HMGB2, increasing HMGB2 expression; SOX5 gene therapy rejuvenates cartilage and alleviates osteoarthritis in aged mice. Genome-wide CRISPRa screening, epigenomic profiling (H3K27ac, H3K4me1 ChIP), SOX5 binding analysis, lentiviral gene therapy in aged mice Cell stem cell High 37832549

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes & development 1404 12414734
1998 A new long form of Sox5 (L-Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene. The EMBO journal 662 9755172
2001 L-Sox5, Sox6 and Sox9 control essential steps of the chondrocyte differentiation pathway. Osteoarthritis and cartilage 294 11680692
2004 The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals sufficient for induction of permanent cartilage. Arthritis and rheumatism 279 15529345
2008 L-Sox5 and Sox6 drive expression of the aggrecan gene in cartilage by securing binding of Sox9 to a far-upstream enhancer. Molecular and cellular biology 245 18559420
2015 The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis. Nucleic acids research 223 26150426
2009 Copy number variation in intron 1 of SOX5 causes the Pea-comb phenotype in chickens. PLoS genetics 179 19521496
2003 Sox5 and Sox6 are required for notochord extracellular matrix sheath formation, notochord cell survival and development of the nucleus pulposus of intervertebral discs. Development (Cambridge, England) 136 12571105
2009 The SoxD transcription factors--Sox5, Sox6, and Sox13--are key cell fate modulators. The international journal of biochemistry & cell biology 135 19647094
2014 MiR-132, miR-15a and miR-16 synergistically inhibit pituitary tumor cell proliferation, invasion and migration by targeting Sox5. Cancer letters 131 25305447
1994 DNA binding and bending properties of the post-meiotically expressed Sry-related protein Sox-5. Nucleic acids research 108 8078769
2014 Sox5 and c-Maf cooperatively induce Th17 cell differentiation via RORγt induction as downstream targets of Stat3. The Journal of experimental medicine 107 25073789
2012 Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features. Human mutation 92 22290657
2012 MiR-194 regulates chondrogenic differentiation of human adipose-derived stem cells by targeting Sox5. PloS one 80 22396742
2008 The transcription factor Sox5 modulates Sox10 function during melanocyte development. Nucleic acids research 78 18703590
1996 Cloning and characterization of SOX5, a new member of the human SOX gene family. Genomics 75 8812465
1999 The energetics of HMG box interactions with DNA: thermodynamics of the DNA binding of the HMG box from mouse sox-5. Journal of molecular biology 74 10588902
2019 Circular RNA DOCK1 promotes bladder carcinoma progression via modulating circDOCK1/hsa-miR-132-3p/Sox5 signalling pathway. Cell proliferation 71 30983072
2008 Transcriptional regulation of chondrogenesis by coactivator Tip60 via chromatin association with Sox9 and Sox5. Nucleic acids research 71 18390577
2008 Myostatin (GDF-8) deficiency increases fracture callus size, Sox-5 expression, and callus bone volume. Bone 70 18852073
2012 L-Sox5 and Sox6 proteins enhance chondrogenic miR-140 microRNA expression by strengthening dimeric Sox9 activity. The Journal of biological chemistry 69 22547066
2017 Sox5 contributes to prostate cancer metastasis and is a master regulator of TGF-β-induced epithelial mesenchymal transition through controlling Twist1 expression. British journal of cancer 65 29123266
2001 Accelerated up-regulation of L-Sox5, Sox6, and Sox9 by BMP-2 gene transfer during murine fracture healing. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 64 11585348
2011 Chondrogenesis of human mesenchymal stem cells mediated by the combination of SOX trio SOX5, 6, and 9 genes complexed with PEI-modified PLGA nanoparticles. Biomaterials 63 21333351
2011 Chondrogenesis of adipose stem cells in a porous PLGA scaffold impregnated with plasmid DNA containing SOX trio (SOX-5,-6 and -9) genes. Biomaterials 63 21421267
2011 SOX5 is a candidate gene for chronic obstructive pulmonary disease susceptibility and is necessary for lung development. American journal of respiratory and critical care medicine 58 21330457
2010 Synovial joint morphogenesis requires the chondrogenic action of Sox5 and Sox6 in growth plate and articular cartilage. Developmental biology 57 20206616
2010 SOX5 controls cell cycle progression in neural progenitors by interfering with the WNT-beta-catenin pathway. EMBO reports 56 20448664
2002 Coamplification of DAD-R, SOX5, and EKI1 in human testicular seminomas, with specific overexpression of DAD-R, correlates with reduced levels of apoptosis and earlier clinical manifestation. Cancer research 56 11912161
2015 Transcription factors Sox5 and Sox6 exert direct and indirect influences on oligodendroglial migration in spinal cord and forebrain. Glia 55 26345464
2017 Long noncoding RNA lnc-sox5 modulates CRC tumorigenesis by unbalancing tumor microenvironment. Cell cycle (Georgetown, Tex.) 54 28632999
2017 Inhibition of TDP43-Mediated SNHG12-miR-195-SOX5 Feedback Loop Impeded Malignant Biological Behaviors of Glioma Cells. Molecular therapy. Nucleic acids 54 29499929
2018 Sox5 is involved in germ-cell regulation and sex determination in medaka following co-option of nested transposable elements. BMC biology 53 29378592
2010 Transcriptional regulation of an axonemal central apparatus gene, sperm-associated antigen 6, by a SRY-related high mobility group transcription factor, S-SOX5. The Journal of biological chemistry 53 20668334
2023 Genome-wide CRISPR activation screening in senescent cells reveals SOX5 as a driver and therapeutic target of rejuvenation. Cell stem cell 51 37832549
2019 miR-497-5p inhibits tumor cell growth and invasion by targeting SOX5 in non-small-cell lung cancer. Journal of cellular biochemistry 51 30816573
2007 Transcriptional activation of cartilage oligomeric matrix protein by Sox9, Sox5, and Sox6 transcription factors and CBP/p300 coactivators. Frontiers in bioscience : a journal and virtual library 51 17485346
2014 Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1. Biochemical and biophysical research communications 50 24607904
2018 Downregulation of miR-139-5p promotes prostate cancer progression through regulation of SOX5. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 49 30551470
2007 Preferential expression and frequent IgG responses of a tumor antigen, SOX5, in glioma patients. International journal of cancer 47 17230535
2002 Identification and characterization of the human long form of Sox5 (L-SOX5) gene. Gene 47 12406576
2011 SHOX interacts with the chondrogenic transcription factors SOX5 and SOX6 to activate the aggrecan enhancer. Human molecular genetics 46 21262861
2019 Apatinib inhibits glycolysis by suppressing the VEGFR2/AKT1/SOX5/GLUT4 signaling pathway in ovarian cancer cells. Cellular oncology (Dordrecht, Netherlands) 45 31325096
2018 Distinct interactions of Sox5 and Sox10 in fate specification of pigment cells in medaka and zebrafish. PLoS genetics 45 29621239
2014 Sox5 functions as a fate switch in medaka pigment cell development. PLoS genetics 45 24699463
2020 NEAT1/miR-193a-3p/SOX5 axis regulates cartilage matrix degradation in human osteoarthritis. Cell biology international 44 31868949
2018 Effect of miR-146a-5p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX5. Experimental and therapeutic medicine 44 29731835
2015 SOX5 promotes epithelial-mesenchymal transition and cell invasion via regulation of Twist1 in hepatocellular carcinoma. Medical oncology (Northwood, London, England) 44 25572815
2011 Electroporation-mediated transfer of SOX trio genes (SOX-5, SOX-6, and SOX-9) to enhance the chondrogenesis of mesenchymal stem cells. Stem cells and development 44 21401405
2020 CircRNA CDR1as knockdown inhibits progression of non-small-cell lung cancer by regulating miR-219a-5p/SOX5 axis. Thoracic cancer 43 31917898
2020 Activation of the SOX-5, SOX-6, and SOX-9 Trio of Transcription Factors Using a Gene-Activated Scaffold Stimulates Mesenchymal Stromal Cell Chondrogenesis and Inhibits Endochondral Ossification. Advanced healthcare materials 41 32329217
2018 Transcription Factor SOX5 Promotes the Migration and Invasion of Fibroblast-Like Synoviocytes in Part by Regulating MMP-9 Expression in Collagen-Induced Arthritis. Frontiers in immunology 41 29706965
2019 FOX-A1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of SOX5. EBioMedicine 40 31147293
2016 MicroRNA-21a-5p Functions on the Regulation of Melanogenesis by Targeting Sox5 in Mouse Skin Melanocytes. International journal of molecular sciences 40 27347933
2019 Long non-coding RNA GAS5 sensitizes renal cell carcinoma to sorafenib via miR-21/SOX5 pathway. Cell cycle (Georgetown, Tex.) 39 29895198
1998 The energetics of HMG box interactions with DNA. Thermodynamic description of the box from mouse Sox-5. Journal of molecular biology 38 9710541
2014 Sox5 Is a DNA-binding cofactor for BMP R-Smads that directs target specificity during patterning of the early ectoderm. Developmental cell 36 25453832
2012 Haploinsufficiency of SOX5, a member of the SOX (SRY-related HMG-box) family of transcription factors is a cause of intellectual disability. European journal of medical genetics 36 23220431
2015 Expressions of Sox9, Sox5, and Sox13 transcription factors in mice testis during postnatal development. Molecular and cellular biochemistry 35 26045173
2017 SOX5/6/21 Prevent Oncogene-Driven Transformation of Brain Stem Cells. Cancer research 33 28687615
2019 SOX5 promotes breast cancer proliferation and invasion by transactivation of EZH2. Oncology letters 32 30854049
2019 Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency. Genetics in medicine : official journal of the American College of Medical Genetics 31 31578471
2018 miR-212-3p reduced proliferation, and promoted apoptosis of fibroblast-like synoviocytes via down-regulating SOX5 in rheumatoid arthritis. European review for medical and pharmacological sciences 31 29424904
2009 Sox5 can suppress platelet-derived growth factor B-induced glioma development in Ink4a-deficient mice through induction of acute cellular senescence. Oncogene 31 19219070
2019 RETRACTED: LncRNA DANCR silence inhibits SOX5-medicated progression and autophagy in osteosarcoma via regulating miR-216a-5p. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 31918278
2009 DNA fingerprinting tags novel altered chromosomal regions and identifies the involvement of SOX5 in the progression of prostate cancer. International journal of cancer 30 19173284
2018 SOX5 interacts with YAP1 to drive malignant potential of non-small cell lung cancer cells. American journal of cancer research 29 29888108
2017 Silencing of the Drosophila ortholog of SOX5 leads to abnormal neuronal development and behavioral impairment. Human molecular genetics 29 28186563
2016 SOX5 is involved in balanced MITF regulation in human melanoma cells. BMC medical genomics 29 26927636
2016 Modulation of IL-6 induced RANKL expression in arthritic synovium by a transcription factor SOX5. Scientific reports 29 27550416
2015 Exome sequencing expands the mechanism of SOX5-associated intellectual disability: A case presentation with review of sox-related disorders. American journal of medical genetics. Part A 29 26111154
2010 Evolutionarily conserved, growth plate zone-specific regulation of the matrilin-1 promoter: L-Sox5/Sox6 and Nfi factors bound near TATA finely tune activation by Sox9. Molecular and cellular biology 29 21173167
2019 SP1-mediated upregulation of lncRNA ILF3-AS1 functions a ceRNA for miR-212 to contribute to osteosarcoma progression via modulation of SOX5. Biochemical and biophysical research communications 28 30819403
2017 Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes. Nature communications 28 28585545
2020 Hypoxia Activates SOX5/Wnt/β-Catenin Signaling by Suppressing MiR-338-3p in Gastric Cancer. Technology in cancer research & treatment 27 32216582
2022 Cyclo-(Phe-Tyr) as a novel cyclic dipeptide compound alleviates ischemic/reperfusion brain injury via JUNB/JNK/NF-κB and SOX5/PI3K/AKT pathways. Pharmacological research 26 35483515
2015 Rearrangement of chromosome bands 12q14~15 causing HMGA2-SOX5 gene fusion and HMGA2 expression in extraskeletal osteochondroma. Oncology reports 26 26043835
2013 Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography. Human molecular genetics 26 23696452
2008 Generation of mice harboring a Sox5 conditional null allele. Genesis (New York, N.Y. : 2000) 25 18543318
2013 Deletion 12p12 involving SOX5 in two children with developmental delay and dysmorphic features. Pediatric neurology 23 23498568
2021 SOX-5 activates a novel RORγt enhancer to facilitate experimental autoimmune encephalomyelitis by promoting Th17 cell differentiation. Nature communications 22 33473108
2021 A novel lncRNA SOX2OT promotes the malignancy of human colorectal cancer by interacting with miR-194-5p/SOX5 axis. Cell death & disease 22 33993197
2017 Construction of PLGA Nanoparticles Coated with Polycistronic SOX5, SOX6, and SOX9 Genes for Chondrogenesis of Human Mesenchymal Stem Cells. ACS applied materials & interfaces 22 28005327
2020 Transactivation of SOX5 by Brachyury promotes breast cancer bone metastasis. Carcinogenesis 21 31713604
2019 SOX5 promotes cell invasion and metastasis via activation of Twist-mediated epithelial-mesenchymal transition in gastric cancer. OncoTargets and therapy 21 31040690
2023 17-DMAG ameliorates neuroinflammation and BBB disruption via SOX5 mediated PI3K/Akt pathway after intracerebral hemorrhage in rats. International immunopharmacology 20 37517381
2022 circ-LDLRAD3 Knockdown Reduces Cisplatin Chemoresistance and Inhibits the Development of Gastric Cancer with Cisplatin Resistance through miR-588 Enrichment-Mediated SOX5 Inhibition. Gut and liver 20 35975639
2020 Neuroprotective effects of SOX5 against ischemic stroke by regulating VEGF/PI3K/AKT pathway. Gene 20 32949698
1998 The mouse Sox5 gene encodes a protein containing the leucine zipper and the Q box. Biochimica et biophysica acta 20 9714725
2021 LncRNA UCC promotes epithelial-mesenchymal transition via the miR-143-3p/SOX5 axis in non-small-cell lung cancer. Laboratory investigation; a journal of technical methods and pathology 19 33824420
2018 TNF-α-Induced SOX5 Upregulation Is Involved in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Through KLF4 Signal Pathway. Molecules and cells 19 29890823
2018 SOX5 induces lung adenocarcinoma angiogenesis by inducing the expression of VEGF through STAT3 signaling. OncoTargets and therapy 19 30254466
2017 SOX5 promotes epithelial-mesenchymal transition in osteosarcoma via regulation of Snail. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 19 28365963
2015 A maternally inherited 16p13.11-p12.3 duplication concomitant with a de novo SOX5 deletion in a male patient with global developmental delay, disruptive and obsessive behaviors and minor dysmorphic features. American journal of medical genetics. Part A 19 25847113
2014 Association study between polymorphisms of PRMT6, PEX10, SOX5, and nonobstructive azoospermia in the Han Chinese population. Biology of reproduction 19 24648396
2014 High levels of SOX5 decrease proliferative capacity of human B cells, but permit plasmablast differentiation. PloS one 19 24945754
2001 Solution structure and backbone dynamics of the DNA-binding domain of mouse Sox-5. Protein science : a publication of the Protein Society 19 11266597
2022 N6-Methyladenosine-induced miR-143-3p promotes intervertebral disc degeneration by regulating SOX5. Bone 18 35878746
2021 CircSEC24A promotes IL-1β-induced apoptosis and inflammation in chondrocytes by regulating miR-142-5p/SOX5 axis. Biotechnology and applied biochemistry 18 33751650
2017 HuR Stabilizes lnc-Sox5 mRNA to Promote Tongue Carcinogenesis. Biochemistry. Biokhimiia 18 28371600