Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins

Antonio A. Postigo, Jennifer L. Depp, Jennifer J. Taylor, Kristen L. Kroll

Research output: Contribution to journalArticlepeer-review

264 Scopus citations

Abstract

Balancing signals derived from the TGFβ family is crucial for regulating cell proliferation and differentiation, and in establishing the embryonic axis during development. TGFβ/BMP signaling leads to the activation and nuclear translocation of Smad proteins, which activate transcription of specific target genes by recruiting P/CAF and p300. The two members of the ZEB family of zinc finger factors (ZEB-1/δEF1 and ZEB-2/SIP1) regulate TGFβ/BMP signaling in opposite ways: ZEB-1/δEF1 synergizes with Smadmediated transcriptional activation, while ZEB-2/SIP1 represses it. Here we report that these antagonistic effects by the ZEB proteins arise from the differential recruitment of transcriptional coactivators (p300 and P/CAF) and corepressors (CtBP) to the Smads. Thus, while ZEB-1/δEF1 binds to p300 and promotes the formation of a p300-Smad transcriptional complex, ZEB-2/SIP1 acts as a repressor by recruiting CtBP. This model of regulation by ZEB proteins also functions in vivo, where they have opposing effects on the regulation of TGFβ family-dependent genes during Xenopus development.

Original languageEnglish
Pages (from-to)2453-2462
Number of pages10
JournalEMBO Journal
Volume22
Issue number10
DOIs
StatePublished - May 15 2003

Keywords

  • BMP
  • CAF
  • CtBP
  • Smad proteins
  • TGFβ
  • ZEB proteins
  • p300-P

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