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

Binding of TGFβ/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/δEF1 and ZEB‐2/SIP1, respectively, regulate gene expression and differenti...

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Bibliographic Details
Published in:The EMBO journal 2003-05, Vol.22 (10), p.2443-2452
Main Author: Postigo, Antonio A
Format: Article
Language:English
Subjects:
BMP signaling
EMBO07
EMBO09
SIP1
Smad proteins
TGFβ
transcriptional regulation
ZEB-1
ZEB-2
δEF1
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Summary:Binding of TGFβ/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/δEF1 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 TGFβ/BMP signaling with opposing effects on this pathway. Both ZEB proteins bind to Smads, but while ZEB‐1/δEF1 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 TGFβ to mediate transcription of TGFβ‐dependent genes and induce growth arrest depends on the presence of endogenous ZEB‐1/δEF1 protein.
ISSN:0261-4189
1460-2075
DOI:10.1093/emboj/cdg225