Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins
Open Access
- 15 May 2003
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 22 (10), 2453-2462
- https://doi.org/10.1093/emboj/cdg226
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 Smad‐mediated 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.Keywords
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