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| Mol. Cell Jan (2002); 9(1):133-43 | |
| Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-beta-mediated induction of the CDK inhibitor p15(Ink4B). | |
| Feng XH, Liang YY, Liang M, Zhai W, Lin X | |
| Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA. xialin@bcm.tmc.edu | |
| Abstract: 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. | |
| [PUBMED: 11804592] |   |
| Copyright © 2009, Tyers Lab, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, All Rights Reserved. |
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| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |