Gene interactions and pathways from curated databases and text-mining
Genes Dev 1999, PMID: 10485843

The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling.

Luo, K; Stroschein, S L; Wang, W; Chen, D; Martens, E; Zhou, S; Zhou, Q

Smad proteins are critical signal transducers downstream of the receptors of the transforming growth factor-beta (TGFbeta) superfamily. On phosphorylation and activation by the active TGFbeta receptor complex, Smad2 and Smad3 form hetero-oligomers with Smad4 and translocate into the nucleus, where they interact with different cellular partners, bind to DNA, regulate transcription of various downstream response genes, and cross-talk with other signaling pathways. Here we show that a nuclear oncoprotein, Ski, can interact directly with Smad2, Smad3, and Smad4 on a TGFbeta-responsive promoter element and repress their abilities to activate transcription through recruitment of the nuclear transcriptional corepressor N-CoR and possibly its associated histone deacetylase complex. Overexpression of Ski in a TGFbeta-responsive cell line renders it resistant to TGFbeta-induced growth inhibition and defective in activation of JunB expression. This ability to overcome TGFbeta-induced growth arrest may be responsible for the transforming activity of Ski in human and avian cancer cells. Our studies suggest a new paradigm for inactivation of the Smad proteins by an oncoprotein through transcriptional repression.

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Text Mining Data

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Manually curated Databases

  • IRef Biogrid Interaction: SKI — SMAD2 (physical association, affinity chromatography technology)
  • MIPS CORUM SMAD4-SNO-SKI complex: SMAD4-SNO-SKI complex complex (SKI-SKIL-SMAD4)
  • MIPS CORUM SMAD2-SKI complex: SMAD2-SKI complex complex (SKI-SMAD2)
  • MIPS CORUM SMAD3-SKI complex: SMAD3-SKI complex complex (SKI-SMAD3)
  • MIPS CORUM SMAD4-SKI complex: SMAD4-SKI complex complex (SKI-SMAD4)
  • MIPS CORUM SMAD2-SKI-NCOR complex: SMAD2-SKI-NCOR complex complex (NCOR1-SKI-SMAD2)
  • MIPS CORUM SMAD3-SKI-NCOR complex: SMAD3-SKI-NCOR complex complex (NCOR1-SKI-SMAD3)
  • MIPS CORUM SMAD4-SKI-NCOR complex: SMAD4-SKI-NCOR complex complex (NCOR1-SKI-SMAD4)
  • IRef Corum Interaction: SMAD3 — SKI (association, anti tag coimmunoprecipitation)
  • IRef Corum Interaction: Complex of SKI-SKIL-SMAD4 (association, affinity chromatography technology)
  • IRef Corum Interaction: Complex of SKI-NCOR1-SMAD3 (association, anti tag coimmunoprecipitation)
  • IRef Corum Interaction: SKI — SMAD2 (association, anti tag coimmunoprecipitation)
  • IRef Corum Interaction: Complex of NCOR1-SKI-SMAD4 (association, anti tag coimmunoprecipitation)
  • IRef Corum Interaction: Complex of NCOR1-SKI-SMAD2 (association, anti tag coimmunoprecipitation)
  • IRef Corum Interaction: SKI — SMAD4 (association, affinity chromatography technology)
  • IRef Hprd Interaction: SKI — SMAD2 (in vitro)
  • IRef Hprd Interaction: SKI — SMAD2 (in vivo)
  • NCI Pathway Database Regulation of nuclear SMAD2/3 signaling: SKI/SIN3/HDAC complex/NCoR1 complex (SKI-NCOR1-SIN3A-SAP30-SAP18-SIN3B-RBBP7-HDAC1-RBBP4-HDAC2) → SMAD3/SMAD4 complex (SMAD3-SMAD4) (modification, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Regulation of nuclear SMAD2/3 signaling: SKI/SIN3/HDAC complex/NCoR1 complex (SKI-NCOR1-SIN3A-SAP30-SAP18-SIN3B-RBBP7-HDAC1-RBBP4-HDAC2) → Cbp/p300/MSG1 complex (EP300_CREBBP-CITED1) (modification, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Regulation of nuclear SMAD2/3 signaling: SKI/SIN3/HDAC complex/NCoR1 complex (SKI-NCOR1-SIN3A-SAP30-SAP18-SIN3B-RBBP7-HDAC1-RBBP4-HDAC2) → SMAD2/SMAD2/SMAD4 complex (SMAD2-SMAD4) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction
  • NCI Pathway Database Regulation of nuclear SMAD2/3 signaling: SKI/SIN3/HDAC complex/NCoR1 complex (SKI-NCOR1-SIN3A-SAP30-SAP18-SIN3B-RBBP7-HDAC1-RBBP4-HDAC2) → Cbp/p300/MSG1 complex (EP300_CREBBP-CITED1) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction
  • Reactome Reaction: SMAD4 → NCOR1 (direct_complex)
  • Reactome Reaction: SMAD4 → NCOR2 (direct_complex)
  • Reactome Reaction: SKI → NCOR2 (reaction)
  • Reactome Reaction: SKI → NCOR1 (direct_complex)
  • Reactome Reaction: SMAD3 → NCOR2 (direct_complex)
  • Reactome Reaction: SKIL → NCOR1 (direct_complex)
  • Reactome Reaction: SMAD4 → SMAD2 (direct_complex)
  • Reactome Reaction: SKIL → SMAD2 (reaction)
  • Reactome Reaction: SKIL → SMAD3 (reaction)
  • Reactome Reaction: SMAD3 → SMAD4 (direct_complex)
  • Reactome Reaction: SKIL → SMAD3 (direct_complex)
  • Reactome Reaction: SKI → SMAD3 (reaction)
  • Reactome Reaction: SKIL → SMAD4 (direct_complex)
  • Reactome Reaction: SKI → SMAD2 (reaction)
  • Reactome Reaction: NCOR1 → SMAD2 (reaction)
  • Reactome Reaction: SMAD3 → NCOR1 (direct_complex)
  • Reactome Reaction: SMAD2 → NCOR2 (reaction)
  • Reactome Reaction: SKIL → SMAD4 (reaction)
  • Reactome Reaction: SKIL → NCOR1 (reaction)
  • Reactome Reaction: SMAD3 → NCOR1 (reaction)
  • Reactome Reaction: SMAD3 → NCOR2 (reaction)
  • Reactome Reaction: SKI → SMAD3 (direct_complex)
  • Reactome Reaction: SKIL → SMAD2 (direct_complex)
  • Reactome Reaction: SKI → SMAD2 (direct_complex)
  • Reactome Reaction: SKI → NCOR2 (direct_complex)
  • Reactome Reaction: SKIL → NCOR2 (direct_complex)
  • Reactome Reaction: SKI → SMAD4 (reaction)
  • Reactome Reaction: SKI → SMAD4 (direct_complex)
  • Reactome Reaction: SMAD2 → NCOR2 (direct_complex)
  • Reactome Reaction: SKIL → NCOR2 (reaction)
  • Reactome Reaction: SKI → NCOR1 (reaction)
  • Reactome Reaction: SMAD4 → NCOR1 (reaction)
  • Reactome Reaction: SMAD4 → NCOR2 (reaction)
  • Reactome Reaction: NCOR1 → SMAD2 (direct_complex)
In total, 119 gene pairs are associated to this article in curated databases