Opposing functions of ZEB proteins in the regulation of the TGFbeta/BMP signaling pathway.
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.
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 Fingers
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 Fingers
EMBO J.
Date: May. 15, 2003
PubMed ID: 12743038
View in: Pubmed Google Scholar
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