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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2002-1-23
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pubmed:abstractText |
The c-Myc oncogene has been implicated in the genesis of diverse human tumors. Ectopic expression of the c-Myc gene in cultured epithelial cells causes resistance to the antiproliferative effects of TGF-beta. However, little is known about the precise mechanisms of c-Myc-mediated TGF-beta resistance. In this study, we reveal that c-Myc physically interacts with Smad2 and Smad3, two specific signal transducers involved in TGF-beta signaling. Through its direct interaction with Smads, c-Myc binds to the Sp1-Smad complex on the promoter of the p15(Ink4B) gene, thereby inhibiting the TGF-beta-induced transcriptional activity of Sp1 and Smad/Sp1-dependent transcription of the p15(Ink4B) gene. These results suggest that oncogenic c-Myc promotes cell growth and cancer development partly by inhibiting the growth inhibitory functions of Smads.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDKN2B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
133-43
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11804592-Cell Cycle Proteins,
pubmed-meshheading:11804592-Cell Line,
pubmed-meshheading:11804592-Cyclin-Dependent Kinase Inhibitor p15,
pubmed-meshheading:11804592-Cyclin-Dependent Kinase Inhibitor p16,
pubmed-meshheading:11804592-Cyclin-Dependent Kinases,
pubmed-meshheading:11804592-DNA-Binding Proteins,
pubmed-meshheading:11804592-Humans,
pubmed-meshheading:11804592-Promoter Regions, Genetic,
pubmed-meshheading:11804592-Protein Binding,
pubmed-meshheading:11804592-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:11804592-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:11804592-Signal Transduction,
pubmed-meshheading:11804592-Smad2 Protein,
pubmed-meshheading:11804592-Smad3 Protein,
pubmed-meshheading:11804592-Sp1 Transcription Factor,
pubmed-meshheading:11804592-Trans-Activators,
pubmed-meshheading:11804592-Transforming Growth Factor beta,
pubmed-meshheading:11804592-Tumor Suppressor Proteins
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pubmed:year |
2002
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pubmed:articleTitle |
Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-beta-mediated induction of the CDK inhibitor p15(Ink4B).
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pubmed:affiliation |
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA. xialin@bcm.tmc.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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