Affinage

SKIL

Ski-like protein · UniProt P12757

Length
684 aa
Mass
77.0 kDa
Annotated
2026-04-28
100 papers in source corpus 27 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SKIL (SnoN) is a transcriptional corepressor that negatively regulates TGF-β signaling by binding Smad2, Smad3, and Smad4 and recruiting histone deacetylase complexes containing N-CoR/SMRT, mSin3, and HDAC to maintain target genes in a repressed state (PMID:10531062, PMID:10811619). Upon TGF-β stimulation, SnoN is rapidly degraded via the ubiquitin–proteasome pathway through multiple E3 ligases—APC/Cdh1, Arkadia (RNF111), and Smurf2—that are recruited by activated Smads, allowing transient target gene activation; SnoN is subsequently re-expressed and binds its own promoter with SMAD4 to terminate signaling in a negative feedback loop (PMID:11691834, PMID:17591695, PMID:22674574). Beyond TGF-β, SnoN functions in neuronal axon growth by interacting with p300 to activate transcription of Ccd1, is regulated by Cdh1-APC in neurons, controls Hippo pathway output by stabilizing TAZ through inhibition of Lats2, promotes Stat5 stability during mammary alveologenesis, and undergoes SUMO modification at Lys-50 by PIAS1/PIASx to regulate myogenesis independently of TGF-β (PMID:16675394, PMID:19339625, PMID:27237790, PMID:22833129, PMID:17202138). SnoN subcellular localization—cytoplasmic in normal cells versus nuclear in cancer cells—determines whether it sequesters Smads in the cytoplasm or represses their transcriptional activity in the nucleus (PMID:16109768).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 Medium

    Establishing that SnoN directly binds DNA and represses transcription through a tripartite domain that interacts with basal transcription factor TAF(II)110 defined SnoN as an active transcriptional repressor rather than a passive binding partner.

    Evidence EMSA, Gal4 fusion reporter, deletion mutagenesis, GST pulldown with TAF(II)110

    PMID:9824161

    Open questions at the time
    • Physiological relevance of direct DNA binding versus Smad-mediated recruitment unclear
    • TAF(II)110 interaction not validated in vivo
  2. 1999 High

    Demonstrating that SnoN binds Smad2/Smad4, recruits N-CoR, and is rapidly degraded upon TGF-β stimulation—then re-expressed to shut off signaling—established the core model of SnoN as both a gatekeeper and feedback terminator of TGF-β transcription.

    Evidence Co-immunoprecipitation, transcriptional reporter assays, pulse-chase degradation experiments in multiple cell lines

    PMID:10531062 PMID:9927733

    Open questions at the time
    • Identity of the E3 ligase mediating degradation was unknown
    • Mechanism of SnoN nuclear export/import not resolved
  3. 2000 High

    Biochemical isolation of a macromolecular SnoN–N-CoR/SMRT–mSin3–HDAC repressor complex defined the enzymatic basis of SnoN-mediated silencing as histone deacetylation.

    Evidence Biochemical fractionation, co-immunoprecipitation, knockout mouse model

    PMID:10811619

    Open questions at the time
    • Specific HDAC isoform(s) required not identified
    • Genome-wide target gene repertoire not mapped
  4. 2001 High

    Reconstitution of Smad3-dependent recruitment of APC/UbcH5 to SnoN's destruction box identified the first E3 ligase responsible for TGF-β-induced SnoN degradation, resolving how ligand signaling removes the repressor.

    Evidence In vitro ubiquitination assay with reconstituted components, site-directed mutagenesis of D-box and lysine residues

    PMID:11691834

    Open questions at the time
    • Relative contribution of APC versus other E3 ligases in different cell types not resolved
    • Cell-cycle phase dependence of APC-mediated degradation not clarified
  5. 2002 Medium

    Mapping the Smad3 interaction surfaces (SE and QPSMT motifs in MH2 domain) and showing Smurf2 induces SnoN ubiquitination revealed a second E3 ligase and explained the specificity of SnoN for TGF-β/activin Smads over BMP Smads.

    Evidence Mutagenesis of Smad3, co-immunoprecipitation, structural mapping using known crystal structure

    PMID:12426322

    Open questions at the time
    • Crystal structure of the SnoN–Smad complex not solved
    • Smurf2-mediated degradation not reconstituted in vitro with purified components
  6. 2003 High

    Demonstrating that oncogenic transformation by SnoN requires simultaneous repression of both R-Smads and Smad4, and that SnoN deficiency in T cells causes augmented TGF-β sensitivity, established in vivo physiological consequences of SnoN-mediated TGF-β repression.

    Evidence Double Smad-binding-site mutagenesis with transformation assays; SnoN-null/hypomorph mouse T cells with anti-TGF-β rescue

    PMID:12764135 PMID:12861029

    Open questions at the time
    • Whether Smad4 and R-Smad binding are simultaneously occupied on chromatin unknown
    • T-cell-intrinsic versus microenvironment contributions not fully separated
  7. 2005 High

    Showing that SnoN is cytoplasmic in normal epithelial cells (where it sequesters Smads) but nuclear in cancer cells resolved a longstanding paradox about how SnoN can be both a tumor suppressor and an oncogene depending on context.

    Evidence Immunofluorescence and subcellular fractionation across primary and cancer cell lines, TGF-β degradation assays

    PMID:16109768

    Open questions at the time
    • Signals controlling nuclear import/export not identified
    • Whether cytoplasmic SnoN is degradation-resistant in vivo not confirmed
  8. 2006 High

    Identifying SnoN as a Cdh1-APC substrate in neurons whose degradation restricts axonal growth revealed a TGF-β-independent function for SnoN in neuronal morphogenesis.

    Evidence Co-immunoprecipitation, ubiquitination assay, shRNA knockdown in granule neurons, in vivo cerebellar analysis

    PMID:14585991 PMID:16675394

    Open questions at the time
    • Transcriptional targets of SnoN in neurons not yet identified at this point
    • Whether Cdh1-APC acts on SnoN in non-neuronal tissues unclear
  9. 2007 High

    Establishing Arkadia (RNF111) as the essential E3 ligase for TGF-β-induced SnoN degradation, requiring a ternary complex with phospho-Smad2/3, resolved the hierarchy among the three known SnoN-targeting E3 ligases and explained signal-dependent gating of degradation.

    Evidence siRNA, dominant-negative mutant, ubiquitination assay, reconstitution in Arkadia-null cancer cells

    PMID:17510063 PMID:17591695

    Open questions at the time
    • Relative tissue-specific contributions of APC, Arkadia, and Smurf2 not systematically compared
    • Structural basis of ternary complex formation unknown
  10. 2007 High

    Demonstrating that SUMO modification of SnoN at Lys-50 by PIAS1/PIASx regulates muscle-specific gene expression independently of TGF-β signaling uncovered a post-translational switch controlling a non-canonical SnoN function in myogenesis.

    Evidence In vivo sumoylation assay, K50R mutagenesis, muscle differentiation assay

    PMID:17202138

    Open questions at the time
    • Identity of SUMO-dependent SnoN interactors in myogenesis unknown
    • Whether SUMO modification alters chromatin targeting not tested
  11. 2009 High

    Identifying p300 as a SnoN coactivator and Ccd1 as a direct transcriptional target in neurons provided the molecular mechanism by which SnoN promotes axonal growth—switching from repressor to activator function via coactivator choice.

    Evidence Gene expression profiling, co-immunoprecipitation with p300, Ccd1 shRNA in rat cerebellum in vivo

    PMID:19339625

    Open questions at the time
    • How SnoN switches from N-CoR to p300 recruitment is mechanistically unresolved
    • Additional neuronal transcription targets not comprehensively mapped
  12. 2012 High

    ChIP and promoter analysis showing that SNON-SMAD4 directly occupies the SKIL promoter TRE to repress its own gene closed the negative feedback loop at the chromatin level and explained signal termination kinetics.

    Evidence ChIP, sequential ChIP, cloned human SKIL promoter-reporter assays

    PMID:22674574

    Open questions at the time
    • Kinetics of SNON re-occupancy after TGF-β pulse not measured genome-wide
    • Whether other TGF-β target promoters use identical autorepression unclear
  13. 2012 High

    Demonstrating that SnoN occupies primitive streak gene promoters with SMAD2 in hESCs, and that its loss causes premature endoderm specification, extended SnoN's gatekeeper role to human pluripotency and early lineage commitment.

    Evidence ChIP in hESCs, siRNA knockdown and overexpression with differentiation marker analysis

    PMID:23154981

    Open questions at the time
    • Whether SnoN acts similarly in mouse ESCs not tested
    • Mechanism of SnoN downregulation during normal endoderm specification unknown
  14. 2012 High

    Showing that SnoN-null mice have severe lactation defects rescued by active Stat5 revealed that SnoN enhances Stat5 protein stability, linking SnoN to JAK-STAT signaling in mammary gland development.

    Evidence Knockout mouse, Stat5 rescue, mammary gland histology

    PMID:22833129

    Open questions at the time
    • Mechanism by which SnoN stabilizes Stat5 (direct binding or indirect) not defined
    • Whether this function is TGF-β-dependent not resolved
  15. 2016 Medium

    Discovering that SnoN interacts with Hippo pathway components to inhibit Lats2-mediated TAZ phosphorylation and degradation revealed a TGF-β-independent oncogenic mechanism operating through cross-pathway regulation.

    Evidence Co-immunoprecipitation, kinase assay, shRNA knockdown, TAZ stability assays in breast cancer cells

    PMID:27237790

    Open questions at the time
    • Structural basis of SnoN–Lats2 interaction unknown
    • Whether SnoN also regulates YAP not tested
    • Single-lab finding awaiting independent confirmation
  16. 2021 High

    Genetic epistasis showing that double knockout of SKI and SnoN rescues Arkadia-deficient iTreg differentiation established that SnoN (and SKI) are the critical Arkadia substrates gating TGF-β-dependent regulatory T cell induction in vivo.

    Evidence Conditional knockout mice, in vitro/in vivo iTreg differentiation, flow cytometry

    PMID:34473197

    Open questions at the time
    • Whether SnoN and SKI have redundant or distinct roles in iTreg specification unclear
    • SnoN targets in Treg-specific gene programs not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of SnoN's cofactor switching (N-CoR versus p300), the signals controlling SnoN nuclear-cytoplasmic shuttling, and the relative tissue-specific contributions of the three E3 ligases (APC, Arkadia, Smurf2) to SnoN turnover.
  • No crystal or cryo-EM structure of SnoN in complex with any partner
  • Genome-wide direct target gene maps across tissues lacking
  • Mechanism of cofactor switching between repression and activation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-392499 Metabolism of proteins 6 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 2
Partners
EP300LATS2RNF111SKISMAD2SMAD3SMAD4SMURF2
Complex memberships
APC/Cdh1N-CoR/SMRT/mSin3/HDAC repressor complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 SnoN (SKIL) interacts directly with Smad2 and Smad4, repressing their transcriptional activity through recruitment of the transcriptional corepressor N-CoR, thereby maintaining TGF-β target genes in a repressed state in the absence of ligand. Co-immunoprecipitation, transcriptional reporter assays, protein interaction studies Science High 10531062
1999 Upon TGF-β stimulation, nuclear accumulation of Smad3 triggers rapid proteasome-dependent degradation of SnoN, allowing activation of TGF-β target genes; SnoN then participates in a negative feedback loop as TGF-β subsequently induces SnoN re-expression to terminate Smad-mediated transactivation. Western blot, reporter assays, pulse-chase degradation experiments Science High 10531062
2001 Smad3 recruits the anaphase-promoting complex (APC) with UbcH5 ubiquitin-conjugating enzymes to SnoN, leading to its ubiquitination in a destruction box (D box)-dependent manner and subsequent proteasomal degradation; both the Smad3-binding site in SnoN and key lysine ubiquitin-attachment residues are required for efficient degradation. In vitro ubiquitination assay, co-immunoprecipitation, site-directed mutagenesis, proteasome inhibitor experiments Genes & development High 11691834
2000 SnoN is a component of a macromolecular repressor complex containing N-CoR/SMRT, mSin3, and histone deacetylase, through which it mediates transcriptional repression and inhibits TGF-β signaling by recruiting this complex to Smad proteins. Biochemical fractionation, co-immunoprecipitation, genetic knockout mouse model The EMBO journal High 10811619
2003 The transforming activity of SnoN requires its ability to bind and repress both receptor-regulated Smads (Smad2/Smad3) and Smad4; Smad2/3 and Smad4 bind to distinct regions of SnoN, and mutation of both binding sites (but not each alone) abolishes TGF-β transcriptional repression, cell cycle arrest resistance, and oncogenic transformation of chicken embryo fibroblasts. Site-directed mutagenesis, co-immunoprecipitation, transcriptional reporter assay, transformation assay (focus formation/soft agar) The Journal of biological chemistry High 12764135
2005 In normal tissues and nontumorigenic epithelial cells, SnoN is predominantly cytoplasmic and antagonizes TGF-β signaling by sequestering Smad proteins in the cytoplasm; upon morphological differentiation or cell-cycle arrest, SnoN translocates to the nucleus. Cytoplasmic SnoN is resistant to TGF-β-induced degradation. In cancer cells, SnoN is exclusively nuclear. Immunofluorescence, subcellular fractionation, co-immunoprecipitation, TGF-β treatment/degradation assays in primary vs. cancer cell lines Proceedings of the National Academy of Sciences of the United States of America High 16109768
2007 Arkadia (an E3 ubiquitin ligase) is absolutely required for TGF-β-induced SnoN degradation; Arkadia interacts with SnoN and constitutively ubiquitinates it, but efficient degradation only occurs when SnoN forms a complex with both Arkadia and phosphorylated Smad2 or Smad3, activating Smad3/Smad4-dependent transcription. siRNA knockdown, dominant-negative mutant, ubiquitination assay, co-immunoprecipitation, luciferase reporter assay, reconstitution in cancer cell line lacking Arkadia Molecular and cellular biology High 17591695
2007 Arkadia induces ubiquitin-dependent degradation of both SnoN and c-Ski (in addition to Smad7) through its RING domain, interacting with these proteins both in their free forms and when bound to Smad proteins, thereby enhancing TGF-β signaling. Co-immunoprecipitation, ubiquitination assay, western blot degradation assays The Journal of biological chemistry High 17510063
2007 TAK1 (MAP3K7) interacts with and phosphorylates SnoN, and this phosphorylation regulates SnoN stability; TAK1 inactivation prevents TGF-β-induced SnoN degradation and impairs induction of TGF-β-responsive genes. Co-immunoprecipitation, in vitro kinase assay, TAK1 loss-of-function, western blot The Journal of biological chemistry Medium 17276978
2006 SnoN is a substrate of Cdh1-APC (anaphase-promoting complex with Cdh1) in neurons; Cdh1 forms a physical complex with SnoN and stimulates its ubiquitin-dependent proteasomal degradation, and SnoN knockdown reduces axonal growth, placing SnoN as a key Cdh1-APC target that promotes axonal morphogenesis in a transcription-dependent manner. Co-immunoprecipitation, ubiquitination assay, shRNA knockdown in neurons, in vivo cerebellar cortex analysis Neuron High 16675394
2008 Smad2 is constitutively phosphorylated and nuclear in cerebellar granule neurons where it forms a physical complex with endogenous SnoN; Smad2 acts upstream of SnoN in the Cdh1-APC pathway to control axonal growth, and Smad2 knockdown stimulates axonal growth and overrides myelin-induced axon growth inhibition. Co-immunoprecipitation of endogenous proteins, genetic epistasis (double knockdown), shRNA in neurons, in vitro axon growth assay The Journal of neuroscience High 18287512
2009 SnoN interacts with the transcriptional coactivator p300, and p300 is required for SnoN-induced axon growth in neurons; SnoN activates transcription of Ccd1 (a signaling scaffold enriched at axon terminals that activates JNK kinase), and Ccd1 knockdown suppresses SnoN-dependent axonal growth in vivo. Gene expression profiling, co-immunoprecipitation, shRNA knockdown in neurons, in vivo parallel fiber analysis in rat cerebellum The Journal of neuroscience High 19339625
1999 Ski and SnoN preferentially form heterodimers over homodimers when co-expressed; tethered Ski:SnoN heterodimers lacking TR/LZ domains are more active in transcriptional repression and cellular transformation than homodimers or monomers. Efficient SnoN homodimerization requires both the TR/LZ domain and an upstream region unique to SnoN, unlike Ski. In vitro co-translation, co-immunoprecipitation, electrophoretic mobility shift assay (DNA binding), transformation assay Nucleic acids research Medium 9927733
2002 Two short segments of Smad3 — the 'SE' sequence in the C-terminal MH2 domain and the adjacent 'QPSMT' sequence — are required for specific interaction with c-Ski and SnoN; these sequences are conserved in Smad2 but absent in Smad1, explaining preferential binding to Smad2/3 over Smad1. Smurf2 induces ubiquitin-dependent degradation of SnoN by positioning it close to the Smad2 linker region. Mutagenesis, co-immunoprecipitation, structural mapping using known Smad MH2 crystal structure The Journal of biological chemistry Medium 12426322
2006 Smurf2 (an E3 ubiquitin ligase) is induced in obstructed kidneys and forms a complex with SnoN, promoting its ubiquitination and proteasomal degradation in vivo; immunodepletion of Smurf2 reduces SnoN ubiquitination in kidney extracts. Immunodepletion, co-immunoprecipitation, ubiquitination assay in kidney extracts, immunohistochemistry Kidney international Medium 16625151
2007 SnoN sumoylation occurs primarily at lysine 50 (Lys-50) and is mediated by E3 SUMO ligases PIAS1 and PIASx, which physically interact with SnoN. SUMO modification does not alter SnoN stability or TGF-β repression, but loss of sumoylation at Lys-50 potently activates muscle-specific gene expression and enhances myotube formation, revealing a TGF-β-independent function of SnoN in myogenesis. In vivo sumoylation assay, site-directed mutagenesis (K50R), co-immunoprecipitation, muscle differentiation assay The Journal of biological chemistry High 17202138
2012 The SNON-SMAD4 complex directly binds the TGF-β response element (TRE) in the SKIL gene proximal promoter and recruits histone deacetylases to repress basal SKIL gene expression; upon TGF-β signaling, SNON is removed from the promoter allowing SMAD complexes to induce SKIL transcription, and the re-expressed SNON-SMAD4 complex then represses its own gene as a negative feedback loop. ChIP assay, sequential ChIP, promoter-reporter (luciferase), cloning of human SKIL promoter The Journal of biological chemistry High 22674574
2012 SNON (SKIL) is expressed in human embryonic stem cells (hESCs) and associates with SMAD2 at promoters of primitive streak and early definitive endoderm marker genes; SNON knockdown causes premature activation of these genes and loss of hESC morphology, while enforced SNON expression inhibits endoderm formation and diverts hESCs toward extraembryonic fate. ChIP assay, siRNA knockdown, overexpression, analysis of hESC differentiation markers Genes & development High 23154981
2016 SnoN interacts with multiple components of the Hippo pathway (including Lats2) to inhibit Lats2 binding to TAZ and subsequent TAZ phosphorylation, leading to TAZ stabilization and enhanced TAZ transcriptional and oncogenic activities; SnoN itself is downregulated by Lats2 activated by the basolateral polarity protein Scribble. Co-immunoprecipitation, kinase assay, shRNA knockdown, TAZ phosphorylation/stability assays, breast cancer cell models Developmental cell Medium 27237790
2021 Arkadia (RNF111) promotes iTreg cell differentiation in CD4+ T cells by inducing degradation of SKI and SnoN; genetic ablation of both SKI and SnoN rescues Arkadia-deficient iTreg differentiation in vitro and in vivo, demonstrating that SKI/SnoN are the critical Arkadia substrates mediating TGF-β-dependent iTreg induction. Conditional knockout mouse (Arkadia in CD4+ T cells), in vitro differentiation assay, double-knockout epistasis, flow cytometry The Journal of experimental medicine High 34473197
2013 SKIL (SnoN) is a driver gene at the 3q26 amplicon; elevated SKIL expression induces cell invasion in immortalized human mammary epithelial cells through upregulation of SLUG (SNAI2), and combined TLOC1 + SKIL expression induces subcutaneous tumor growth in vivo. Gain-of-function genetic screen, shRNA loss-of-function, invasion assay, xenograft mouse model, proteomic studies Cancer discovery Medium 23764425
2012 SnoN suppresses BMP-induced hypertrophic maturation of chondrocytes by inhibiting BMP signaling downstream of Smad1/5/8 activation, specifically by suppressing Id1 expression; SnoN expression is highest in articular cartilage of adult mice and co-localizes with phospho-Smad2/3 in prehypertrophic chondrocytes. siRNA knockdown, overexpression, BMP-responsive reporter assay, expression analysis in mouse growth plate and human OA cartilage The Journal of biological chemistry Medium 22767605
2012 SnoN coordinates TGF-β and prolactin signaling in mammary epithelial cells by enhancing Stat5 protein stability; SnoN-/- mice display severe defects in alveologenesis and lactogenesis that can be rescued by active Stat5, demonstrating SnoN promotes Stat5 signaling to control lactation. Knockout mouse model, rescue by active Stat5, mammary gland morphogenesis analysis Development High 22833129
2003 Sno-deficient T cells show augmented TGF-β sensitivity; Sno-dependent suppression of TGF-β signaling is required for normal T-cell proliferation following receptor ligation, as the proliferation defect in Sno hypomorph and null mice is reversed by anti-TGF-β antibodies or exogenous IL-2. IL-2 and IL-4 production is reduced in mutant T cells. Targeted gene deletion (hypomorph and null mice), T-cell proliferation assay, anti-TGF-β rescue, cytokine measurement Molecular and cellular biology High 12861029
2024 NSUN2 promotes m5C methylation of SKIL mRNA, which is recognized by YBX1 to stabilize SKIL transcripts; elevated SKIL increases TAZ activation to promote colorectal cancer progression. m5C-methylated RNA immunoprecipitation, RNA stability assay, bisulfite sequencing, NSUN2 knockout mouse, YBX1 interaction studies Clinical and translational medicine Medium 38468490
2020 SKIL promotes tumorigenesis and immune escape of NSCLC by interacting with TAZ (co-immunoprecipitation), upregulating TAZ to activate autophagy and suppress the STING pathway; silencing TAZ cancels the effects of SKIL overexpression. Co-immunoprecipitation, lentiviral overexpression/knockdown, colony formation assay, xenograft and syngeneic mouse models, flow cytometry for T cell infiltration Cell death & disease Medium 33268765
1998 SnoN binds a specific DNA sequence (GTCTAGAC) and represses transcription through a tripartite repression domain; subdomain II interacts with TAF(II)110 via a quenching mechanism of transcriptional repression. Two subdomains (II and III) are required for DNA binding and cellular transformation. Electrophoretic mobility shift assay, Gal4 fusion reporter assay, deletion mutagenesis, transformation assay, GST pulldown with TAF(II)110 Oncogene Medium 9824161
2018 FMRP directly interacts with lncRNA TUG1 and decreases its stability; TUG1 binds to SnoN and negatively modulates the SnoN-Ccd1 pathway to control axonal development in neurons. RNA immunoprecipitation, co-immunoprecipitation, axon growth assay in FMRP-deficient neurons Human molecular genetics Low 29211876

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro-oncology 905 32328653
2021 Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 627 34932393
1999 Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein. Science (New York, N.Y.) 433 10531062
2009 Ski and SnoN, potent negative regulators of TGF-beta signaling. Cell research 227 19114989
2010 The SNO-proteome: causation and classifications. Current opinion in chemical biology 203 21087893
2010 GPS-SNO: computational prediction of protein S-nitrosylation sites with a modified GPS algorithm. PloS one 199 20585580
2001 Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN. Genes & development 186 11691834
2001 Ski/Sno and TGF-beta signaling. Cytokine & growth factor reviews 178 11312113
1989 Isolation of human cDNA clones of ski and the ski-related gene, sno. Nucleic acids research 166 2762147
2007 Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. Molecular and cellular biology 148 17591695
2002 An EGFR/Ebi/Sno pathway promotes delta expression by inactivating Su(H)/SMRTER repression during inductive notch signaling. Cell 147 12230979
2007 Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-beta signaling. The Journal of biological chemistry 144 17510063
2006 Cell-intrinsic regulation of axonal morphogenesis by the Cdh1-APC target SnoN. Neuron 143 16675394
2022 EANO, SNO and Euracan consensus review on the current management and future development of intracranial germ cell tumors in adolescents and young adults. Neuro-oncology 110 34724065
2019 Recent developments and future directions in adult lower-grade gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus. Neuro-oncology 97 30753579
1998 The highly conserved, coregulated SNO and SNZ gene families in Saccharomyces cerevisiae respond to nutrient limitation. Journal of bacteriology 94 9791124
2006 Dual role of SnoN in mammalian tumorigenesis. Molecular and cellular biology 88 17074815
2003 The transforming activity of Ski and SnoN is dependent on their ability to repress the activity of Smad proteins. The Journal of biological chemistry 88 12764135
2000 The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice. The EMBO journal 87 10811619
1993 Sequence and biological activity of chicken snoN cDNA clones. Oncogene 83 8426750
2021 Unique challenges for glioblastoma immunotherapy-discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank. Neuro-oncology 82 33367885
2020 SNO-MLP (S-Nitrosylation of Muscle LIM Protein) Facilitates Myocardial Hypertrophy Through TLR3 (Toll-Like Receptor 3)-Mediated RIP3 (Receptor-Interacting Protein Kinase 3) and NLRP3 (NOD-Like Receptor Pyrin Domain Containing 3) Inflammasome Activation. Circulation 81 31902237
2008 TGFbeta-Smad2 signaling regulates the Cdh1-APC/SnoN pathway of axonal morphogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 80 18287512
2002 Up-regulated transcriptional repressors SnoN and Ski bind Smad proteins to antagonize transforming growth factor-beta signals during liver regeneration. The Journal of biological chemistry 76 12023281
2013 Systematic interrogation of 3q26 identifies TLOC1 and SKIL as cancer drivers. Cancer discovery 72 23764425
2003 Downregulation of Smad transcriptional corepressors SnoN and Ski in the fibrotic kidney: an amplification mechanism for TGF-beta1 signaling. Journal of the American Society of Nephrology : JASN 72 14638915
2001 SNO is a probable target for gene amplification at 3q26 in squamous-cell carcinomas of the esophagus. Biochemical and biophysical research communications 71 11511096
2005 Cytoplasmic SnoN in normal tissues and nonmalignant cells antagonizes TGF-beta signaling by sequestration of the Smad proteins. Proceedings of the National Academy of Sciences of the United States of America 66 16109768
2006 Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury. Kidney international 63 16625151
2020 Selective Ethanol Oxidation Reaction at the Rh-SnO2 Interface. Advanced materials (Deerfield Beach, Fla.) 62 33314444
2015 p53 Represses the Oncogenic Sno-MiR-28 Derived from a SnoRNA. PloS one 62 26061048
2005 SnoN is a cell type-specific mediator of transforming growth factor-beta responses. The Journal of biological chemistry 60 15677458
2021 SnO2-Doped ZnO/Reduced Graphene Oxide Nanocomposites: Synthesis, Characterization, and Improved Anticancer Activity via Oxidative Stress Pathway. International journal of nanomedicine 59 33447029
1997 Proto-oncogene Sno expression, alternative isoforms and immediate early serum response. Nucleic acids research 59 9207045
2024 NSUN2 promotes colorectal cancer progression by enhancing SKIL mRNA stabilization. Clinical and translational medicine 58 38468490
2006 Downregulation of SnoN expression in obstructive nephropathy is mediated by an enhanced ubiquitin-dependent degradation. Journal of the American Society of Nephrology : JASN 58 16959829
2022 EANO - EURACAN - SNO Guidelines on circumscribed astrocytic gliomas, glioneuronal, and neuronal tumors. Neuro-oncology 56 35908833
2002 The spliced leader-associated RNA is a trypanosome-specific sn(o) RNA that has the potential to guide pseudouridine formation on the SL RNA. RNA (New York, N.Y.) 55 11911368
1993 SnoI, a novel alternatively spliced isoform of the ski protooncogene homolog, sno. Nucleic acids research 53 8233802
2009 A SnoN-Ccd1 pathway promotes axonal morphogenesis in the mammalian brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 52 19339625
2017 'SNO'-Storms Compromise Protein Activity and Mitochondrial Metabolism in Neurodegenerative Disorders. Trends in endocrinology and metabolism: TEM 50 29097102
2020 Synthesis of a carbon dots modified g-C3N4/SnO2 Z-scheme photocatalyst with superior photocatalytic activity for PPCPs degradation under visible light irradiation. Journal of hazardous materials 49 32659572
2012 Transforming growth factor-β/SMAD Target gene SKIL is negatively regulated by the transcriptional cofactor complex SNON-SMAD4. The Journal of biological chemistry 46 22674574
2021 Facile construction of S-scheme SnO2/g-C3N4 photocatalyst for improved photoactivity. Chemosphere 44 34863724
2014 Species-specific alternative splicing leads to unique expression of sno-lncRNAs. BMC genomics 44 24734784
2012 SnoN suppresses maturation of chondrocytes by mediating signal cross-talk between transforming growth factor-β and bone morphogenetic protein pathways. The Journal of biological chemistry 44 22767605
2018 Graphene blended with SnO2 and Pd-Pt nanocages for sensitive non-enzymatic electrochemical detection of H2O2 released from living cells. Analytica chimica acta 43 29523247
2002 Two short segments of Smad3 are important for specific interaction of Smad3 with c-Ski and SnoN. The Journal of biological chemistry 43 12426322
2016 Oxymatrine Inhibits Renal Tubular EMT Induced by High Glucose via Upregulation of SnoN and Inhibition of TGF-β1/Smad Signaling Pathway. PloS one 42 27010330
2007 Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling. Molecular and cellular neurosciences 42 17292623
2005 Requirement for the SnoN oncoprotein in transforming growth factor beta-induced oncogenic transformation of fibroblast cells. Molecular and cellular biology 41 16314499
2020 SKIL facilitates tumorigenesis and immune escape of NSCLC via upregulating TAZ/autophagy axis. Cell death & disease 40 33268765
2011 Efficient TGF-β/SMAD signaling in human melanoma cells associated with high c-SKI/SnoN expression. Molecular cancer 40 21211030
2019 Phosphate-Passivated SnO2 Electron Transport Layer for High-Performance Perovskite Solar Cells. ACS applied materials & interfaces 38 31525907
2021 Arkadia-SKI/SnoN signaling differentially regulates TGF-β-induced iTreg and Th17 cell differentiation. The Journal of experimental medicine 36 34473197
2010 SnoN in mammalian development, function and diseases. Current opinion in pharmacology 35 20822955
2007 TAK1 MAPK kinase kinase mediates transforming growth factor-beta signaling by targeting SnoN oncoprotein for degradation. The Journal of biological chemistry 35 17276978
2017 Biology and clinical relevance of noncoding sno/scaRNAs. Trends in cardiovascular medicine 34 28869095
2014 Ellagic acid mitigates SNO-PDI induced aggregation of Parkinsonian biomarkers. ACS chemical neuroscience 34 25247703
1999 Heterodimers of the SnoN and Ski oncoproteins form preferentially over homodimers and are more potent transforming agents. Nucleic acids research 34 9927733
2020 miR‑574‑5p attenuates proliferation, migration and EMT in triple‑negative breast cancer cells by targeting BCL11A and SOX2 to inhibit the SKIL/TAZ/CTGF axis. International journal of oncology 33 32319565
2014 SnoN as a novel negative regulator of TGF-β/Smad signaling: a target for tailoring organ fibrosis. American journal of physiology. Heart and circulatory physiology 33 25380815
2017 Down-regulation of miR-23a inhibits high glucose-induced EMT and renal fibrogenesis by up-regulation of SnoN. Human cell 32 28707079
2017 Fumonisin B1 induces oxidative stress in oesophageal (SNO) cancer cells. Toxicon : official journal of the International Society on Toxinology 31 29233736
2016 SnoN Antagonizes the Hippo Kinase Complex to Promote TAZ Signaling during Breast Carcinogenesis. Developmental cell 30 27237790
2010 The role of SnoN in transforming growth factor beta1-induced expression of metalloprotease-disintegrin ADAM12. The Journal of biological chemistry 30 20457602
2021 Photoelectrochemical Assay Based on SnO2/BiOBr p-n Heterojunction for Ultrasensitive DNA Detection. Analytical chemistry 29 34524810
2017 SnO2 hollow nanotubes: a novel and efficient support matrix for enzyme immobilization. Scientific reports 29 29127386
2008 SnoN in TGF-beta signaling and cancer biology. Current molecular medicine 29 18537639
2014 The proteasome inhibitor, MG132, attenuates diabetic nephropathy by inhibiting SnoN degradation in vivo and in vitro. BioMed research international 28 25003128
2014 Potential therapeutic targets for oral cancer: ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF, CD70. PloS one 28 25029526
2005 Characterization of Sno expression in malignant melanoma. International journal of oncology 28 15809735
2022 BMP-7 ameliorates partial epithelial-mesenchymal transition by restoring SnoN protein level via Smad1/5 pathway in diabetic kidney disease. Cell death & disease 27 35314669
2020 A novel Au-SnO2-rGO ternary nanoheterojunction catalyst for UV-LED induced photocatalytic degradation of clothianidin: Identification of reactive intermediates, degradation pathway and in-depth mechanistic insight. Journal of hazardous materials 27 32402954
2019 miR-130a-3p inhibition protects against renal fibrosis in vitro via the TGF-β1/Smad pathway by targeting SnoN. Experimental and molecular pathology 27 31836508
2013 Cooperative involvement of NFAT and SnoN mediates transforming growth factor-β (TGF-β) induced EMT in metastatic breast cancer (MDA-MB 231) cells. Clinical & experimental metastasis 27 23832742
2009 TGF-beta repressors SnoN and Ski are implicated in human colorectal carcinogenesis. Cellular oncology : the official journal of the International Society for Cellular Oncology 27 19096149
2007 Molecular basis for the cell type specific induction of SnoN expression by hepatocyte growth factor. Journal of the American Society of Nephrology : JASN 27 17625116
1995 The ski/sno protooncogene family in hematopoietic development. Blood 27 7662963
2012 The SMAD2/3 corepressor SNON maintains pluripotency through selective repression of mesendodermal genes in human ES cells. Genes & development 26 23154981
2010 Transforming growth factor-beta regulator SnoN modulates mammary gland branching morphogenesis, postlactational involution, and mammary tumorigenesis. Cancer research 26 20460516
2019 SNHG14 promotes the tumorigenesis and metastasis of colorectal cancer through miR-32-5p/SKIL axis. In vitro cellular & developmental biology. Animal 25 31471872
2016 Fusaric acid induces oxidative stress and apoptosis in human cancerous oesophageal SNO cells. Toxicon : official journal of the International Society on Toxinology 25 27956242
2008 Ski/SnoN expression in the sequence metaplasia-dysplasia-adenocarcinoma of Barrett's esophagus. Human pathology 25 18261624
2017 Nitrosopersulfide (SSNO-) decomposes in the presence of sulfide, cyanide or glutathione to give HSNO/SNO-: consequences for the assumed role in cell signalling. Interface focus 24 28382204
2012 SnoN regulates mammary gland alveologenesis and onset of lactation by promoting prolactin/Stat5 signaling. Development (Cambridge, England) 24 22833129
2012 SnoN/SKIL modulates proliferation through control of hsa-miR-720 transcription in esophageal cancer cells. Biochemical and biophysical research communications 23 23154181
2015 Recurrent SKIL-activating rearrangements in ETS-negative prostate cancer. Oncotarget 22 25749039
2013 Phospholipid Scramblase 1, an interferon-regulated gene located at 3q23, is regulated by SnoN/SkiL in ovarian cancer cells. Molecular cancer 22 23621864
2008 Overexpression of SnoN/SkiL, amplified at the 3q26.2 locus, in ovarian cancers: a role in ovarian pathogenesis. Molecular oncology 22 19383336
2003 Defective T-cell activation is associated with augmented transforming growth factor Beta sensitivity in mice with mutations in the Sno gene. Molecular and cellular biology 22 12861029
1998 A domain necessary for the transforming activity of SnoN is required for specific DNA binding, transcriptional repression and interaction with TAF(II)110. Oncogene 22 9824161
2020 Smad2 and Smad3 play antagonistic roles in high glucose-induced renal tubular fibrosis via the regulation of SnoN. Experimental and molecular pathology 20 31917288
2018 Interplay between FMRP and lncRNA TUG1 regulates axonal development through mediating SnoN-Ccd1 pathway. Human molecular genetics 20 29211876
2017 Repression of Smad3 by Stat3 and c-Ski/SnoN induces gefitinib resistance in lung adenocarcinoma. Biochemical and biophysical research communications 20 28115165
2012 SnoN signaling in proliferating cells and postmitotic neurons. FEBS letters 20 22710173
2008 Clinical significance of the expression of c-Ski and SnoN, possible mediators in TGF-beta resistance, in primary cutaneous melanoma. Journal of dermatological science 20 18782659
2005 Light-induced inhibition of papain by a {Mn-NO}6 nitrosyl: identification of papain-SNO adduct by mass spectrometry. Journal of inorganic biochemistry 20 15927266
2007 Transforming growth factor-beta-independent regulation of myogenesis by SnoN sumoylation. The Journal of biological chemistry 19 17202138
2015 The downregulation of SnoN expression in human renal proximal tubule epithelial cells under high-glucose conditions is mediated by an increase in Smurf2 expression through TGF-β1 signaling. International journal of molecular medicine 18 26743567