Abstract
Balancing signals derived from the TGFbeta family is crucial for regulating cell proliferation and differentiation, and in establishing the embryonic axis during development. TGFbeta/BMP signaling leads to the activation and nuclear translocation of Smad proteins, which activate transcription of specific target genes by recruiting P/CAF and p300. The two members of the ZEB family of zinc finger factors (ZEB-1/deltaEF1 and ZEB-2/SIP1) regulate TGFbeta/BMP signaling in opposite ways: ZEB-1/deltaEF1 synergizes with Smad-mediated transcriptional activation, while ZEB-2/SIP1 represses it. Here we report that these antagonistic effects by the ZEB proteins arise from the differential recruitment of transcriptional coactivators (p300 and P/CAF) and corepressors (CtBP) to the Smads. Thus, while ZEB-1/deltaEF1 binds to p300 and promotes the formation of a p300-Smad transcriptional complex, ZEB-2/SIP1 acts as a repressor by recruiting CtBP. This model of regulation by ZEB proteins also functions in vivo, where they have opposing effects on the regulation of TGFbeta family-dependent genes during Xenopus development.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alcohol Oxidoreductases
-
Animals
-
Bone Morphogenetic Proteins / metabolism
-
Cell Line
-
DNA-Binding Proteins / metabolism*
-
Embryo, Nonmammalian / anatomy & histology
-
Embryo, Nonmammalian / physiology
-
Gene Expression Regulation*
-
Homeodomain Proteins / metabolism
-
Humans
-
In Situ Hybridization
-
Nuclear Proteins / metabolism
-
Phosphoproteins / metabolism
-
Protein Binding
-
Repressor Proteins / metabolism*
-
Signal Transduction / physiology*
-
Smad Proteins
-
Trans-Activators / metabolism*
-
Transcription Factors / metabolism*
-
Transcription, Genetic
-
Transforming Growth Factor beta / metabolism
-
Xenopus Proteins*
-
Xenopus laevis / growth & development
-
Xenopus laevis / physiology
-
Zinc Finger E-box Binding Homeobox 2
-
Zinc Finger E-box-Binding Homeobox 1
-
Zinc Fingers
Substances
-
Bone Morphogenetic Proteins
-
DNA-Binding Proteins
-
Homeodomain Proteins
-
Nuclear Proteins
-
Phosphoproteins
-
Repressor Proteins
-
Smad Proteins
-
Trans-Activators
-
Transcription Factors
-
Transforming Growth Factor beta
-
Xenopus Proteins
-
ZEB1 protein, human
-
ZEB2 protein, Xenopus
-
ZEB2 protein, human
-
Zinc Finger E-box Binding Homeobox 2
-
Zinc Finger E-box-Binding Homeobox 1
-
Alcohol Oxidoreductases
-
C-terminal binding protein