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Opposing functions of ZEB proteins in the regulation of the TGFbeta/BMP signaling pathway.

The EMBO journal | May 15, 2003

Binding of TGFbeta/BMP factors to their receptors leads to translocation of Smad proteins to the nucleus where they activate transcription of target genes. The two-handed zinc finger proteins encoded by Zfhx1a and Zfhx1b, ZEB-1/deltaEF1 and ZEB-2/SIP1, respectively, regulate gene expression and differentiation programs in a number of tissues. Here I demonstrate that ZEB proteins are also crucial regulators of TGFbeta/BMP signaling with opposing effects on this pathway. Both ZEB proteins bind to Smads, but while ZEB-1/deltaEF1 synergizes with Smad proteins to activate transcription, promote osteoblastic differentiation and induce cell growth arrest, the highly related ZEB-2/SIP1 protein has the opposite effect. Finally, the ability of TGFbeta to mediate transcription of TGFbeta-dependent genes and induce growth arrest depends on the presence of endogenous ZEB-1/deltaEF1 protein.

Pubmed ID: 12743038 RIS Download

Mesh terms: Animals | Bone Morphogenetic Proteins | Cell Line | DNA-Binding Proteins | Gene Expression Regulation | Genes, Reporter | Homeodomain Proteins | Humans | Protein Binding | Repressor Proteins | Signal Transduction | Smad Proteins | Smad2 Protein | Smad3 Protein | Trans-Activators | Transcription Factors | Transcription, Genetic | Transforming Growth Factor beta | Zinc Finger E-box-Binding Homeobox 1 | Zinc Fingers

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