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Opposing functions of ZEB proteins in the regulation of the TGFβ/BMP signaling pathway
Author(s) -
Postigo Antonio A.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg225
Subject(s) - biology , smad , microbiology and biotechnology , smad2 protein , transcription factor , r smad , signal transduction , dna binding protein , bmpr2 , bone morphogenetic protein , zinc finger , transcription (linguistics) , bone morphogenetic protein 2 , transforming growth factor , gene , genetics , endoglin , stem cell , cd34 , linguistics , philosophy , in vitro
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.