Genes Dev 1999,
PMID: 10485843
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
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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