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PMID: 12743038 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 22 ·No. 10 ·2003-05-15 ·Pages 2443-52

Postigo AA

Abstract

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/genetics,metabolism Cell Line DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation Genes, Reporter Homeodomain Proteins/genetics,metabolism Humans Protein Binding Repressor Proteins/genetics,metabolism Signal Transduction/physiology Smad Proteins Smad2 Protein Smad3 Protein Trans-Activators/genetics,metabolism Transcription Factors/genetics,metabolism Transcription, Genetic Transforming Growth Factor beta/genetics,metabolism Zinc Finger E-box Binding Homeobox 2 Zinc Finger E-box-Binding Homeobox 1 Zinc Fingers
Chemicals
Bone Morphogenetic Proteins DNA-Binding Proteins Homeodomain Proteins Repressor Proteins SMAD2 protein, human SMAD3 protein, human Smad Proteins Smad2 Protein Smad3 Protein Trans-Activators Transcription Factors Transforming Growth Factor beta ZEB1 protein, human ZEB1 protein, rat ZEB2 protein, human Zinc Finger E-box Binding Homeobox 2 Zinc Finger E-box-Binding Homeobox 1
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Postigo Antonio A
Division of Molecular Oncology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA. apostigo@im.wustl.edu
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg225
Email
apostigo@im.wustl.edu
Published
2003-05-15
Pages
2443-52
Language
English
Region
England
NLM ID
8208664
PMCID
PMC155983
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg225 PMC Full Text View journal details
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