Affinage

SOX2

Transcription factor SOX-2 · UniProt P48431

Length
317 aa
Mass
34.3 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOX2 is an HMG-domain pioneer transcription factor that binds and locally distorts nucleosomal DNA to control chromatin accessibility, lineage specification, and stem-cell maintenance across diverse tissues (PMID:32350470, PMID:37691488). Cryo-EM shows SOX2 engages nucleosomal DNA at superhelical location 2, detaches terminal DNA from the histone octamer, and repositions the histone H4 N-terminal tail to increase accessibility (PMID:32350470), and acute SOX2 depletion collapses thousands of accessible chromatin sites within an hour, with the subset it maintains being highly predictive of gene expression (PMID:37691488). In pluripotency it cooperates with partner factors: OCT4-SOX2 differentially distort nucleosomal DNA depending on motif placement (PMID:32327602), SOX2 and KLF4 form a functional reprogramming core that co-binds the genome and remodels pluripotency enhancers (PMID:31722212), and during early embryogenesis SOX2 first occupies pre-accessible enhancers opened by other factors before redistributing to open or poise new enhancers (PMID:38096290). SOX2 functions principally as a transcriptional activator, since substituting a VP16 activation domain enhances reprogramming while a repressor fusion abolishes it (PMID:28813671), and its intrinsically disordered C-terminal region rearranges upon DNA/nucleosome binding to expose two activation domains (PMID:38365983). Beyond DNA, SOX2 binds double-stranded RNA via an HMG-box-associated RNA-binding motif, forming ternary RNA/SOX2/DNA complexes whose disruption impairs reprogramming (PMID:32286318, PMID:32016422). SOX2 partner usage is context-dependent in cancer: it switches from OCT4 to p63 in squamous carcinomas to co-occupy loci and drive oncogenes such as ETV4 (PMID:24590290), partners with KLF5 to acquire new binding sites and activate endogenous retroviruses (PMID:33972779), and represses the Hippo activators NF2 and WWC1 to potentiate YAP (PMID:25832504, PMID:31560173). It also reprograms metabolism, transactivating the SLC2A1/GLUT1 enhancer with p63 to fuel glucose influx and antioxidant capacity in squamous tumors (PMID:31412252) and driving prostate-specific metabolic target genes (PMID:35067686). SOX2 protein stability is set by opposing ubiquitin enzymes—UBE2S-mediated K11 ubiquitination at K123 and the CUL4A-DET1-COP1 ligase promote degradation, while deubiquitylases OTUD7B and PSMD7 stabilize it (PMID:26292759, PMID:30405104, PMID:38494478)—and its nuclear localization and activity are controlled by CDK1 and AKT signaling (PMID:30297536, PMID:26498353). Developmentally, SOX2 is required dosage-dependently for inner-ear neurogenesis (PMID:28642583), salivary acinar cell survival (PMID:28623666), and lens/nasal placode induction with Oct-1 (PMID:17140559), while acting as a context-dependent tumor suppressor that restrains Wnt-driven gastric adenoma (PMID:27498859).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2006 High

    Established that SOX2 acts combinatorially with a POU partner to drive a defined developmental enhancer, framing its activity as context-dependent and partner-driven rather than autonomous.

    Evidence Genetic epistasis in double-mutant mice plus in vitro transactivation and transgenic enhancer assays at the Pax6 lens enhancer with Oct-1

    PMID:17140559

    Open questions at the time
    • Did not resolve nucleosome-level binding mechanism
    • Limited to lens/nasal placode context
  2. 2014 High

    Showed SOX2 switches its transcription-factor partner in a tissue-specific manner, explaining how the same factor produces different transcriptional outputs in pluripotency versus cancer.

    Evidence ChIP-seq, co-IP and siRNA knockdown in squamous cell carcinoma defining SOX2-p63 co-occupancy and ETV4 dependence

    PMID:24590290

    Open questions at the time
    • Did not define structural basis of partner selection
    • Generality across other SCC subtypes not fully mapped
  3. 2017 High

    Defined SOX2 as a transcriptional activator that establishes de novo enhancers during reprogramming, distinguishing activation from repression as the functionally relevant output.

    Evidence VP16/HP1 activation/repression domain swaps with reprogramming efficiency assays and ChIP-seq

    PMID:28813671

    Open questions at the time
    • Mechanism of de novo enhancer selection not resolved
    • Did not address chromatin-opening kinetics
  4. 2020 High

    Resolved at near-atomic detail how SOX2 acts as a pioneer factor, showing it distorts nucleosomal DNA and detaches terminal DNA to increase accessibility, alone and with OCT4.

    Evidence Cryo-EM structures of SOX2 and OCT4-SOX2 bound to nucleosomes

    PMID:32327602 PMID:32350470

    Open questions at the time
    • Static structures do not capture chromatin-opening dynamics in cells
    • Role of partner stoichiometry in vivo unaddressed
  5. 2020 High

    Revealed an unexpected RNA-binding function, defining a C-terminal RNA-binding motif that forms ternary RNA/SOX2/DNA complexes and contributes to reprogramming.

    Evidence In vitro binding, CLIP and fRIP-seq in ES cells, plus RBM deletion and reprogramming assays

    PMID:32016422 PMID:32286318

    Open questions at the time
    • Functional consequence of most SOX2-RNA interactions unknown
    • Whether RNA binding tunes DNA binding in vivo unresolved
  6. 2020 Medium

    Connected SOX2 to R-loop biology, showing it inhibits Ddx5 resolvase activity to facilitate reprogramming, linking its nucleic-acid binding to chromatin/genome maintenance.

    Evidence Co-IP, R-loop profiling and reprogramming assays with RNaseH1 perturbation

    PMID:32704541

    Open questions at the time
    • Single-lab co-IP for Sox2-Ddx5 interaction
    • Direct effect on R-loop structures at SOX2 targets not mapped
  7. 2023 High

    Distinguished functional from incidental SOX2 binding by showing acute depletion rapidly collapses a subset of accessible sites that predict gene expression, defining the productive pioneer activity.

    Evidence Acute protein depletion with ATAC-seq, nascent transcription and CRISPR validation

    PMID:37691488

    Open questions at the time
    • What distinguishes productive from dispensable sites mechanistically
    • Generalizability beyond ES cells
  8. 2023 High

    Mapped SOX2 enhancer logic in vivo and at its own locus, showing it occupies pre-accessible enhancers before redistributing, and that distal autonomous and context-dependent DHSs control its own expression.

    Evidence In vivo embryo ChIP-seq/ATAC-seq across stages and endogenous locus engineering (Big-IN) of the Sox2 enhancer cluster

    PMID:36931273 PMID:38096290

    Open questions at the time
    • Factors directing SOX2 redistribution not fully identified
    • Enhancer rules may differ in non-embryonic tissues
  9. 2024 High

    Provided the biophysical basis for SOX2 activation, showing DNA/nucleosome binding rearranges the disordered C-terminal region to expose activation domains.

    Evidence Single-molecule FRET, NMR and molecular simulations

    PMID:38365983

    Open questions at the time
    • Whether IDR rearrangement recruits specific coactivators unproven
    • In-cell relevance of conformational ensemble not tested
  10. 2024 High

    Consolidated SOX2 as a substrate of opposing ubiquitin/deubiquitin enzymes, establishing post-translational stability control as a major regulatory layer governing its levels in development and cancer.

    Evidence Ubiquitination/deubiquitination assays, site-directed mutagenesis (K123), and rescue experiments across ES, NPC and cancer systems (UBE2S, CUL4A-DET1-COP1, OTUD7B, PSMD7)

    PMID:26292759 PMID:30405104 PMID:38494478

    Open questions at the time
    • Upstream signals selecting ligase vs deubiquitylase context unknown
    • Crosstalk with CDK1/AKT phosphorylation not integrated
  11. 2024 High

    Defined tissue-specific transcriptional programs and partner-dependent oncogenic functions, from metabolic reprogramming to Hippo/Wnt modulation and squamous ERV activation.

    Evidence ChIP-seq, CRISPR KO, metabolic assays and organoid/tumor models across squamous, prostate, gastric and esophageal contexts (p63, KLF5, NF2/WWC1, SLC2A1)

    PMID:25832504 PMID:27498859 PMID:31412252 PMID:33972779 PMID:35067686

    Open questions at the time
    • How identical HMG domain achieves divergent tissue target selection unresolved
    • Direct vs indirect status of some metabolic targets not all ChIP-validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how SOX2 integrates its DNA, RNA, partner-factor, conformational, and post-translational regulatory inputs into a single predictive model of context-specific target selection.
  • No unifying framework linking partner identity to genomic redistribution
  • Crosstalk between RNA binding, IDR dynamics and chromatin opening unmapped
  • Signaling-to-stability-to-localization axis not reconstituted

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0140110 transcription regulator activity 3 GO:0003723 RNA binding 2 GO:0042393 histone binding 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
COP1DDX5KLF4KLF5OTUD7BPOU2F1POU5F1TP63

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 Cryo-EM structures of SOX2 HMG domain bound to nucleosomes show that SOX2 binds and locally distorts nucleosomal DNA at superhelical location 2, facilitates detachment of terminal nucleosomal DNA from the histone octamer to increase DNA accessibility, and repositions the N-terminal tail of histone H4 (including K16), suggesting incompatibility with higher-order nucleosome stacking. Cryo-electron microscopy structure determination Nature High 32350470
2020 Cryo-EM structures of OCT4-SOX2 bound to nucleosomes at two preferred positions show that OCT4-SOX2 differentially distort nucleosomal DNA depending on motif location; at one position, OCT4-SOX2 removes DNA from histone H2A and H3, while at an inverted motif only local DNA distortions are induced. OCT4 uses one of its two DNA-binding domains to engage DNA in both structures. Cryo-electron microscopy structure determination with base-pair resolution in vitro TF engagement mapping Science High 32327602
2020 SOX2 directly binds RNA through its HMG DNA-binding domain in vitro with high affinity, primarily interacting with double-stranded RNA in a non-sequence-specific fashion. In mouse embryonic stem cells, UV-crosslinked immunoprecipitation (CLIP) confirmed direct SOX2-RNA binding in vivo, identifying over a thousand SOX2-RNA interactions by fRIP-seq. In vitro binding assays, UV-crosslinked immunoprecipitation (CLIP), fRIP-seq Nature communications High 32286318
2020 SOX2 binds RNA via a 60-amino-acid RNA-binding motif (RBM) positioned C-terminally of the HMG box, forming ternary RNA/SOX2/DNA complexes. Deletion of the RBM does not affect target gene selection but reduces binding to pluripotency-related transcripts, alters exon usage, and impairs reprogramming of somatic cells to pluripotency. In vitro binding assays, domain deletion mutagenesis, reprogramming efficiency assays, RNA binding assays in mouse and human cells Nucleic acids research High 32016422
2015 SOX2 antagonizes the Hippo pathway to maintain cancer stem cells in osteosarcomas by directly repressing two Hippo activators, NF2 (Merlin) and WWC1 (Kibra), leading to exaggerated YAP function. This SOX2-Hippo axis is conserved in glioblastomas. ChIP, luciferase reporter assays, siRNA knockdown, tumor growth assays Nature communications High 25832504
2014 In squamous cell carcinomas (SCCs), SOX2 preferentially interacts with the transcription factor p63 (rather than OCT4 as in ES cells), and SOX2-p63 co-occupy a large number of genomic loci. SOX2 and p63 jointly regulate gene expression including the oncogene ETV4, which is essential for SOX2-amplified SCC cell survival. ChIP-seq, co-immunoprecipitation, gene expression analysis, siRNA knockdown The Journal of clinical investigation High 24590290
2018 CDK1 physically interacts with SOX2 and promotes its nuclear localization, phosphorylation, and transcriptional activity. Blockade or knockdown of CDK1 reduces phosphorylation, nuclear localization, and transcriptional activity of SOX2, and CDK1-driven tumor-initiating capacity is substantially reduced by SOX2 knockout. Proteomic co-immunoprecipitation, pharmacologic CDK1 inhibition, CRISPR knockout, spheroid and xenograft assays Cancer research High 30297536
2018 The ubiquitin-conjugating enzyme UBE2S mediates K11-linked polyubiquitin chain formation at SOX2-K123, marking SOX2 for proteasomal degradation. UBE2S fine-tunes SOX2 protein levels and reinforces ES cell self-renewal while repressing SOX2-mediated neural ectodermal differentiation. Ubiquitination assays, site-directed mutagenesis (K123 residue), proteasome inhibition, ES cell differentiation assays Cell death and differentiation High 26292759
2018 The E3 ubiquitin ligase complex CUL4A-DET1-COP1 ubiquitylates SOX2 (with COP1 as the substrate receptor interacting directly with SOX2) to promote its degradation, while the deubiquitylase OTUD7B removes polyubiquitin chains from SOX2 to stabilize it. These opposing enzymes govern SOX2 protein stability during neural progenitor cell differentiation. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, western blot during NPC differentiation Nature communications High 30405104
2015 AKT physically interacts with SOX2 protein and modulates its subcellular distribution. AKT kinase inhibition results in enhanced cytoplasmic retention of SOX2 (presumably via impaired nuclear import) and successive cytoplasmic proteasomal degradation. Ectopic SOX2 expression restores clonogenicity and tumorigenicity of AKT-inhibited cells. Co-immunoprecipitation, subcellular fractionation, pharmacologic AKT inhibition, rescue overexpression experiments, xenograft assays Oncotarget Medium 26498353
2006 SOX2 forms a complex with Oct-1 (encoded by Pou2f1) at specific DNA-binding sites to cooperatively transactivate the Pax6 lens ectoderm enhancer. Genetic combination of Sox2 and Pou2f1 mutant alleles causes impaired lens placode induction and complete failure of nasal placode induction in mice. Genetic epistasis (double mutant mice), in vitro transactivation assays, transgenic mouse enhancer assays Developmental biology High 17140559
2020 Sox2 interacts with the reprogramming barrier factor Ddx5 and inhibits the resolvase activity of Ddx5 on R-loops, thereby facilitating somatic cell reprogramming. Sox2, but not other Yamanaka factors, overcomes the inhibitory effects of RNaseH1 activity loss on reprogramming. Co-immunoprecipitation, R-loop profiling, reprogramming efficiency assays with RNaseH1 depletion/inactivation Science advances Medium 32704541
2017 SOX2 acts as a transcriptional activator during reprogramming: substituting SOX2-VP16 for wild-type SOX2 increased reprogramming efficiency and rate, whereas SOX2-HP1 (a repressor fusion) eliminated reprogramming. At early reprogramming stages, DNA-bound SOX2 was embedded in putative enhancers, about half of which were created de novo. Domain swap (VP16/HP1 fusions), reprogramming efficiency assays, ChIP-seq Cell reports High 28813671
2019 SOX2 directly represses NF2 and WWC1 in esophageal squamous cell carcinoma, activating YAP1. Multiple SOX2 binding peaks at the WWC1 locus and inverse correlation between SOX2 and WWC1 expression were found, and SOX2 gain-of-function promoted nuclear YAP1 expression while SOX2 silencing inhibited YAP1 activation. ChIP-seq, gene expression analysis, SOX2 overexpression/knockdown, YAP1 localization assays Cancer medicine Medium 31560173
2016 Sox2 loss in gastric epithelial cells enhances tumor formation in Apc-deficient gastric cells by inducing Tcf/Lef-dependent transcription and upregulating intestinal metaplasia-associated genes, identifying Sox2 as a context-dependent tumor suppressor in the stomach that restrains Wnt-driven adenoma formation. ChIP-seq, conditional Sox2 knockout mice, Apc/Wnt-driven tumor model, luciferase reporter assays Cell reports High 27498859
2011 SOX2 knockdown in melanoma cells with high constitutive SOX2 expression resulted in 4.5-fold decreased invasiveness in vitro, associated with 87.8% reduction in MMP-3 mRNA. Conversely, SOX2 overexpression increased invasiveness 3.8-fold. MMP-3 knockdown inhibited invasion similarly but to a lesser degree than SOX2 knockdown. siRNA knockdown, overexpression, in vitro invasion assay, RT-PCR array of 84 invasion-related genes Laboratory investigation Medium 22184093
2019 Squamous lineage transcription factors p63 and SOX2 transactivate the intronic enhancer cluster of SLC2A1 (GLUT1), driving exceptional glucose influx in squamous cell carcinomas. Elevated glucose influx fuels NADPH/GSH generation and heightens anti-oxidative capacity in SCC tumors. ChIP-seq, luciferase reporter assays for enhancer transactivation, metabolic assays (NADPH/GSH measurement), pharmacologic glucose restriction Cell reports Medium 31412252
2020 TRIM24 activates Sox2 expression at the transcriptional level in glioblastoma cells, as demonstrated by chromatin immunoprecipitation, reporter gene assay, and rescue experiments showing that TRIM24 participation in GBM infiltrative dissemination depends on Sox2. Chromatin immunoprecipitation, reporter gene assay, TRIM24 knockdown, Sox2 rescue experiments, xenotransplantation Neuro-oncology Medium 32492707
2021 Oncogenic Sox2 in esophageal squamous cell carcinoma acquires new binding sites when partnered with Klf5, enhances activity of oncogenes such as Stat3, and activates endogenous retroviruses, inducing expression of double-stranded RNA and dependence on the RNA editing enzyme ADAR1. Sox2 ChIP-seq in murine esophageal organoids, epigenetic landscape mapping, ATAC-seq, transgenic carcinoma models Nature genetics High 33972779
2019 Sox2 and Klf4 are a functional core for pluripotency induction: polycistronic expression of Sox2 and Klf4 alone (without exogenous Oct4) was sufficient to reprogram fibroblasts and neural progenitor cells to iPSCs. Sox2 and Klf4 cooperatively bind across the genome, leading to epigenetic remodeling of pluripotency genes, with stoichiometry of the two factors being essential. iPSC reprogramming assays, ChIP-seq, epigenetic analysis, genome-wide co-binding Cell reports High 31722212
2023 In mouse E3.5 inner cell mass, SOX2 occupies preaccessible enhancers (opened by early TFs TFAP2C and NR5A2) rather than opening global enhancers, then widely redistributes to open new enhancers or poise them for future activation as cells adopt naive and formative pluripotency states. SOX2 ChIP-seq in mouse embryos from E3.5 to E7.5, ATAC-seq, genetic ablation Science High 38096290
2023 In mouse ES cells, two DNase I hypersensitive sites (DHSs) in the distal Sox2 enhancer cluster are each individually sufficient for long-range activation of Sox2 expression, requiring only a handful of key TF recognition sequences. Three nearby DHSs are context-dependent, showing no activity alone but augmenting the activity of the autonomous DHSs. Large-scale endogenous locus engineering (Big-IN), scarless DHS deletions/rearrangements/inversions, surgical TF motif alterations, multiple mESC clone analysis Molecular cell High 36931273
2023 Acute depletion of SOX2 results in rapid loss of thousands of accessible chromatin sites within one hour, demonstrating SOX2's role as a pioneer factor maintaining chromatin accessibility. Open chromatin sites maintained by SOX2 are highly predictive of gene expression, while other SOX2 binding sites are largely dispensable for gene regulation. Acute protein depletion, ATAC-seq, nascent transcription analysis, CRISPR-Cas9 regulatory element validation at Klf2 locus The EMBO journal High 37691488
2024 DNA and nucleosome binding by SOX2 induces major rearrangements in the conformational ensemble of SOX2's intrinsically disordered C-terminal region (IDR), redistributing interdomain interactions and variably exposing two activation domains critical for transcription. The IDR dynamics are guided by weak and dynamic charge interactions with the folded HMG DNA-binding domain. Single-molecule FRET, NMR spectroscopy, molecular simulations Nature communications High 38365983
2019 Small endogenous fluctuations of SOX2 and OCT4 protein levels in G1 (but not S phase) bias ES cell fate commitment. High OCT4 levels increased chromatin accessibility at differentiation-associated enhancers as measured by ATAC-seq on cells gated for different endogenous factor levels. Knock-in reporter fusion ES cell lines, FACS-gated ATAC-seq, directed differentiation assays Molecular systems biology Medium 31556488
2010 Sox2 activated proliferation of respiratory epithelial cells in vivo, associated with increased cyclin D1, and activated transcription of FoxM1 in vitro. Sox2 also induced ectopic differentiation of alveolar epithelial cells to those with morphologic and molecular characteristics of conducting airway epithelium. Conditional transgenic mouse overexpression, cell cycle gene expression analysis, in vitro transcription assays American journal of respiratory cell and molecular biology Medium 20855650
2017 SOX2 is required for inner ear neurogenesis: conditional SOX2 deletion at otocyst stages caused near-absence of NEUROG1-expressing neuroblasts, increased cell death in the neurosensory epithelium, and significantly reduced cochleovestibular ganglion volume. Heterozygotes showed milder neurogenesis reduction, indicating SOX2 dosage-dependence. Conditional knockout mice (Cre-lox), immunofluorescence, fate-mapping experiments Scientific reports High 28642583
2020 Sox2 directly controls fibronectin fibrillogenesis in Schwann cells, providing a highly oriented fibronectin matrix that supports their organization and directional migration. Sox2 also regulates extracellular matrix and migration genes and formation of focal adhesions, and Sox2-dependent fibronectin matrix is required for neuron migration along oriented Schwann cells. Sox2 overexpression/knockdown in RSC96 line, fibronectin matrix imaging, migration assays, co-culture with neurons, in vivo sciatic nerve regeneration Scientific reports Medium 32029747
2014 Conditional deletion of Sox2 from nascent cholinergic amacrine cells in the retina perturbed the normal ratio of cells in the ganglion cell layer versus inner nuclear layer and induced a bistratifying morphology with dendrites distributed to both ON and OFF strata. Conditional knockout mice (Cre-lox), quantitative cell counting, morphological analysis The Journal of neuroscience Medium 25057212
2017 SOX2 ablation in dermal papilla (DP) cells of hair follicles causes a phenotypic switch from eumelanin to pheomelanin production. Mechanistically, Sox2 directly regulates Agouti (temporal upregulation) and Corin (downregulation) in DP, and BMP signaling regulation by Sox2 downregulates MC1R, Dct, and Tyr in melanocytes. Conditional Sox2 knockout in DP using Lepr-Cre, pigmentation analysis, gene expression, BMP signaling assays Cell reports Medium 35858560
2019 In esophageal squamous cell carcinoma, elevated Sox2 signaling causes endothelial-mesenchymal transitions (EndMTs) by interacting with JMJD5, inducing EndMTs in cerebral endothelial cells. EC-specific suppression of Sox2 normalized endothelial differentiation and lumen formation, improving cerebral AVMs. Conditional Sox2 overexpression/suppression, co-immunoprecipitation, epigenetic profiling, ChIP-seq for JMJD5 as Sox2 target The Journal of clinical investigation Medium 31232700
2022 CRISPR-mediated SOX2 deletion in castration-resistant prostate cancer cells reveals that SOX2 promotes metabolic reprogramming including increased glycolysis, glycolytic capacity, basal/maximal oxidative respiration, and spare respiratory capacity. SOX2 ChIP-seq identified prostate-specific target genes (CERK, ECHS1, HS6SDT1, LPCAT4, PFKP, SLC16A3, SLC46A1, TST) distinct from canonical embryonic SOX2 targets. CRISPR KO, Seahorse metabolic assays, SOX2 ChIP-seq, metabolomics Oncogene High 35067686
2016 In lung cancer cells, SOX2 bound the EPCAM promoter to induce EpCAM-p21Cip1-cyclin A2 signaling promoting cell proliferation, while SOX9 bound the SLUG promoter for invasion. Ectopic SOX2 expression inhibited SOX9 with increased H3K9me2 on the SOX9 promoter, establishing an epigenetic switch between SOX2 and SOX9 controlling cancer cell plasticity. ChIP, promoter binding assays, HDAC inhibition, ectopic expression, histone methylation analysis Cancer research Medium 27758880
2021 DYRK1A promotes differentiation of glioblastoma stem cells by deactivating CDK5, which results in decreased SOX2 expression. The DYRK1A-CDK5-SOX2 pathway represents a regulatory axis controlling GSC stemness; DYRK1A inhibition insulates self-renewing GSCs from differentiation by maintaining CDK5 activity and SOX2 levels. DYRK1A inhibition/activation, CDK5 knockdown, SOX2 expression analysis, GSC differentiation assays International journal of molecular sciences Medium 33924599
2024 PSMD7 (a deubiquitinating enzyme) deubiquitinates and stabilizes SOX2 protein in pancreatic cancer cells, increasing SOX2 protein levels and subsequently activating Notch1 signaling. Restoration of SOX2 expression abrogated the antitumor effect of PSMD7 knockdown. Co-immunoprecipitation, ubiquitination assays, PSMD7 knockdown, SOX2 rescue experiments, in vivo tumor assays Cell & bioscience Medium 38494478
2011 miR-126 inhibits SOX2 expression by targeting two binding sites in the 3'-UTR of SOX2 mRNA. Luciferase assays and gain/loss-of-function experiments confirmed this post-transcriptional repression. SOX2 overexpression was found to downregulate PLAC1, identifying PLAC1 as a downstream target of SOX2. Luciferase reporter assays (3'-UTR), miRNA gain/loss-of-function, siRNA knockdown, microarray after SOX2 overexpression PloS one Medium 21304604
2016 Sox2 interferes with Wnt signaling in tooth development by binding to β-catenin; Sox2 knockdown results in failure of cell migration from molar 1 to molar 2, and degradation of Wnt signaling caused by Sox2 knockdown results in lack of cell migration. Temporal Sox2 knockdown, DiI cell tracking assay, Wnt signaling analysis Cell and tissue research Medium 26846112
2019 SOX2 expression in bladder cancer induces IGF2 expression (gene expression profiling), and SOX2-mediated spheroid formation under low-serum stress is inhibited by pharmacologic inhibition of AKT (MK2206) or IGF1R (linsitinib), placing IGF2-IGF1R-AKT downstream of SOX2. SOX2 overexpression/silencing, gene expression profiling, pharmacologic AKT and IGF1R inhibition, spheroid formation assays Scientific reports Low 32427884
2017 SOX2 targets acinar-specific genes and is essential for the survival of acinar but not ductal cells during salivary gland development. Genetic ablation of SOX2 results in failure to establish acini. Parasympathetic nerves regulate acinar cell generation via regulation of SOX2. Conditional SOX2 knockout, ChIP-seq for SOX2 target genes in salivary gland, genetic lineage tracing eLife High 28623666

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 SOX2 in development and cancer biology. Seminars in cancer biology 287 31412296
2009 Sox2 roles in neural stem cells. The international journal of biochemistry & cell biology 278 19733254
2014 SOX2 and cancer: current research and its implications in the clinic. Clinical and translational medicine 220 25114775
2013 The multiple roles for Sox2 in stem cell maintenance and tumorigenesis. Cellular signalling 217 23416461
2020 Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function. Nature 206 32350470
2015 Sox2 antagonizes the Hippo pathway to maintain stemness in cancer cells. Nature communications 206 25832504
2020 Mechanisms of OCT4-SOX2 motif readout on nucleosomes. Science (New York, N.Y.) 187 32327602
2005 SOX2 anophthalmia syndrome. American journal of medical genetics. Part A 184 15812812
2017 The dark side of SOX2: cancer - a comprehensive overview. Oncotarget 178 28388544
2020 Functional characterization of SOX2 as an anticancer target. Signal transduction and targeted therapy 176 32728033
2019 SOX2 protein biochemistry in stemness, reprogramming, and cancer: the PI3K/AKT/SOX2 axis and beyond. Oncogene 151 31477842
2014 SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas. The Journal of clinical investigation 148 24590290
2011 MicroRNA-126 inhibits SOX2 expression and contributes to gastric carcinogenesis. PloS one 148 21304604
2011 SOX2 expression and amplification in gliomas and glioma cell lines. Cancer genomics & proteomics 143 21518820
2007 Expression of LHX3 and SOX2 during mouse inner ear development. Gene expression patterns : GEP 133 17604700
2016 Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication. Journal of experimental & clinical cancer research : CR 123 27225481
2018 CDK1 Interacts with Sox2 and Promotes Tumor Initiation in Human Melanoma. Cancer research 105 30297536
2010 Expression of pax6 and sox2 in adult olfactory epithelium. The Journal of comparative neurology 104 20852734
2010 Sox2 activates cell proliferation and differentiation in the respiratory epithelium. American journal of respiratory cell and molecular biology 102 20855650
2006 Sox2 and Pou2f1 interact to control lens and olfactory placode development. Developmental biology 94 17140559
2011 SOX2 contributes to melanoma cell invasion. Laboratory investigation; a journal of technical methods and pathology 92 22184093
2014 Sox2 expression involvement in the oncogenicity and radiochemoresistance of oral cancer stem cells. Oral oncology 90 25456004
2020 The Sox2 transcription factor binds RNA. Nature communications 87 32286318
2017 SOX2 regulates acinar cell development in the salivary gland. eLife 81 28623666
2021 Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence. Nature genetics 80 33972779
2015 Overview of the roles of Sox2 in stem cell and development. Biological chemistry 78 25781683
2018 miR-145-5p Suppresses Breast Cancer Progression by Inhibiting SOX2. The Journal of surgical research 72 30694767
2008 Sox2 expression in brain tumors: a reflection of the neuroglial differentiation pathway. The American journal of surgical pathology 70 18162777
2019 p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas. Cell reports 69 31412252
2018 Targeting SOX2 in anticancer therapy. Expert opinion on therapeutic targets 67 30366514
2022 SOX2 mediates metabolic reprogramming of prostate cancer cells. Oncogene 65 35067686
2018 Sox2 haploinsufficiency primes regeneration and Wnt responsiveness in the mouse cochlea. The Journal of clinical investigation 62 29553487
2019 Endogenous fluctuations of OCT4 and SOX2 bias pluripotent cell fate decisions. Molecular systems biology 61 31556488
2016 Sox2 Suppresses Gastric Tumorigenesis in Mice. Cell reports 61 27498859
2018 Dynamic ubiquitylation of Sox2 regulates proteostasis and governs neural progenitor cell differentiation. Nature communications 60 30405104
2009 Differential expression of SOX2 and SOX17 in testicular germ cell tumors. American journal of clinical pathology 57 19369635
2016 Epigenetic Switch between SOX2 and SOX9 Regulates Cancer Cell Plasticity. Cancer research 56 27758880
2020 R-loops coordinate with SOX2 in regulating reprogramming to pluripotency. Science advances 53 32704541
2023 Synthetic regulatory genomics uncovers enhancer context dependence at the Sox2 locus. Molecular cell 52 36931273
2011 SOX2 and nestin expression in human melanoma: an immunohistochemical and experimental study. Experimental dermatology 51 21410764
2015 Ube2s regulates Sox2 stability and mouse ES cell maintenance. Cell death and differentiation 48 26292759
2019 Sox2: A Regulatory Factor in Tumorigenesis and Metastasis. Current protein & peptide science 46 30907312
2014 Sox2 regulates cholinergic amacrine cell positioning and dendritic stratification in the retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 25057212
2020 Concurrent binding to DNA and RNA facilitates the pluripotency reprogramming activity of Sox2. Nucleic acids research 42 32016422
2020 TRIM24 promotes stemness and invasiveness of glioblastoma cells via activating Sox2 expression. Neuro-oncology 41 32492707
2017 SOX2 is required for inner ear neurogenesis. Scientific reports 41 28642583
2016 Paradoxical role of SOX2 in gastric cancer. American journal of cancer research 40 27186426
2019 Sox2 promotes expression of the ST6Gal-I glycosyltransferase in ovarian cancer cells. Journal of ovarian research 39 31610800
2022 Deconstructing Sox2 Function in Brain Development and Disease. Cells 38 35626641
2019 Unique and redundant roles of SOX2 and SOX17 in regulating the germ cell tumor fate. International journal of cancer 38 31583686
2015 Molecular and functional interactions between AKT and SOX2 in breast carcinoma. Oncotarget 38 26498353
2016 Sox2: regulation of expression and contribution to brain tumors. CNS oncology 36 27230973
2023 Multifaceted SOX2-chromatin interaction underpins pluripotency progression in early embryos. Science (New York, N.Y.) 35 38096290
2020 Sox2 controls Schwann cell self-organization through fibronectin fibrillogenesis. Scientific reports 35 32029747
2019 Elevated endothelial Sox2 causes lumen disruption and cerebral arteriovenous malformations. The Journal of clinical investigation 35 31232700
2019 SOX2 Expression Is an Independent Predictor of Oral Cancer Progression. Journal of clinical medicine 35 31640140
2012 Sox2 regulation of hair cell development: incoherence makes sense. Hearing research 35 23154195
2017 OCT4 and SOX2 Work as Transcriptional Activators in Reprogramming Human Fibroblasts. Cell reports 33 28813671
2008 Hypermethylation of SOX2 gene in hydatidiform mole and choriocarcinoma. Reproductive sciences (Thousand Oaks, Calif.) 33 18836133
2019 Sox2 and Klf4 as the Functional Core in Pluripotency Induction without Exogenous Oct4. Cell reports 32 31722212
2014 Slug promotes hepatocellular cancer cell progression by increasing sox2 and nanog expression. Oncology reports 32 25339068
2013 Clinicopathologic implications of EpCAM and Sox2 expression in breast cancer. Clinical breast cancer 32 24201161
2007 Expression of Sox2 in mature and immature teratomas of central nervous system. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 32 17464316
2023 SOX2-associated signaling pathways regulate biological phenotypes of cancers. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 31 36738502
2008 Expression of Sox2 in mouse taste buds and its relation to innervation. Cell and tissue research 31 18379823
2016 SOX2 inhibits metastasis in gastric cancer. Journal of cancer research and clinical oncology 29 26960758
2024 Deubiquitinase PSMD7 facilitates pancreatic cancer progression through activating Nocth1 pathway via modifying SOX2 degradation. Cell & bioscience 28 38494478
2017 Sox2 is dispensable for primary melanoma and metastasis formation. Oncogene 28 28368416
2012 Oct4 and Sox2 are overexpressed in human neuroblastoma and inhibited by chemotherapy. Oncology reports 28 22576801
2020 SOX2 and squamous cancers. Seminars in cancer biology 27 32905832
2014 Clinicopathologic significance of Sox2, CD44 and CD44v6 expression in intrahepatic cholangiocarcinoma. Pathology oncology research : POR 27 24482053
2021 SOX21 modulates SOX2-initiated differentiation of epithelial cells in the extrapulmonary airways. eLife 26 34286693
2018 SOX2 expression diminishes with ageing in several tissues in mice and humans. Mechanisms of ageing and development 26 29574045
2024 DNA binding redistributes activation domain ensemble and accessibility in pioneer factor Sox2. Nature communications 24 38365983
2023 Reciprocal regulation of LINC00941 and SOX2 promotes progression of esophageal squamous cell carcinoma. Cell death & disease 24 36717549
2023 Pioneer activity distinguishes activating from non-activating SOX2 binding sites. The EMBO journal 24 37691488
2021 MicroRNAs regulating SOX2 in cancer progression and therapy response. Expert reviews in molecular medicine 24 34583803
2020 Critical role of SOX2-IGF2 signaling in aggressiveness of bladder cancer. Scientific reports 24 32427884
2023 LncRNA GSCAR promotes glioma stem cell maintenance via stabilizing SOX2 expression. International journal of biological sciences 23 37063420
2022 SOX2 transcription factor binding and function. Development (Cambridge, England) 23 35861233
2017 Sox2 regulates astrocytic and vascular development in the retina. Glia 23 29178409
2020 circ_0005273 promotes thyroid carcinoma progression by SOX2 expression. Endocrine-related cancer 22 31693489
2019 Sox2 dosage: A critical determinant in the functions of Sox2 in both normal and tumor cells. Journal of cellular physiology 22 31344986
2018 Crosstalk between SOX2 and cytokine signaling in endometrial carcinoma. Scientific reports 22 30510261
2019 SIX1 represses senescence and promotes SOX2-mediated cellular plasticity during tumorigenesis. Scientific reports 21 30723235
2022 SOX2 and PRAME in the "reprogramming" of seminoma cells. Pathology, research and practice 20 35930824
2021 DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells. International journal of molecular sciences 20 33924599
2019 SOX2 participates in spermatogenesis of Zhikong scallop Chlamys farreri. Scientific reports 20 30635613
2014 Expression of Sox2 in cervical squamous cell carcinoma. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 20 24659665
2013 SOX2 expression in hypopharyngeal, laryngeal, and sinonasal squamous cell carcinoma. Human pathology 20 24656096
2022 Sox2 in the dermal papilla regulates hair follicle pigmentation. Cell reports 19 35858560
2019 SOX2 antagonizes WWC1 to drive YAP1 activation in esophageal squamous cell carcinoma. Cancer medicine 18 31560173
2016 Sox2 contributes to tooth development via Wnt signaling. Cell and tissue research 18 26846112
2014 Neuronal expression of SOX2 is enriched in specific hypothalamic cell groups. Journal of chemical neuroanatomy 18 25263324
2023 Capsaicin Reduces Cancer Stemness and Inhibits Metastasis by Downregulating SOX2 and EZH2 in Osteosarcoma. The American journal of Chinese medicine 17 37120706
2019 Glioma SOX2 expression decreased after adjuvant therapy. BMC cancer 17 31718604
2016 Sox2: To crest or not to crest? Seminars in cell & developmental biology 17 27592260
2018 Regulation of glioma cell invasion by 3q26 gene products PIK3CA, SOX2 and OPA1. Brain pathology (Zurich, Switzerland) 16 30403311
2023 High Sox2 expression predicts taste lineage competency of lingual progenitors in vitro. Development (Cambridge, England) 15 36794954
2022 OCT4, SOX2 and NANOG co-regulate glycolysis and participate in somatic induced reprogramming. Cytotechnology 15 35733702

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