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EMBO J. 2003 May 15;22(10):2443-52.

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

Author information

  • Division of Molecular Oncology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA. apostigo@im.wustl.edu

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.

PMID:
12743038
[PubMed - indexed for MEDLINE]
PMCID:
PMC155983
Free PMC Article

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