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

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.

Pubmed ID: 12743038

Authors

  • Postigo AA

Journal

The EMBO journal

Publication Data

May 15, 2003

Associated Grants

None

Mesh Terms

  • Animals
  • Bone Morphogenetic Proteins
  • Cell Line
  • DNA-Binding Proteins
  • Gene Expression Regulation
  • Genes, Reporter
  • Homeodomain Proteins
  • Humans
  • Protein Binding
  • Repressor Proteins
  • Signal Transduction
  • Smad Proteins
  • Smad2 Protein
  • Smad3 Protein
  • Trans-Activators
  • Transcription Factors
  • Transcription, Genetic
  • Transforming Growth Factor beta
  • Zinc Fingers