SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5'-CACCT sequences in candidate target genes

Kristin Verschueren, Jacques E. Remacle, Clara Collart, Harry Kraft, Betty S. Baker, Przemko Tylzanowski, Luc Nelles, Gunther Wuytens, Ming Tsan Su, Rolf Bodmer, James C. Smith, Danny Huylebroeck*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

381 引文 斯高帕斯(Scopus)

摘要

Activation of transforming growth factor β receptors causes the phosphorylation and nuclear translocation of Smad proteins, which then participate in the regulation of expression of target genes. We describe a novel Smad-interacting protein, SIP1, which was identified using the yeast two-hybrid system. Although SIP1 interacts with the MH2 domain of receptor- regulated Smads in yeast and in vitro, its interaction with full-length Smads in mammalian cells requires receptor-mediated Smad activation. SIP1 is a new member of the δEF1/Zfh-1 family of two-handed zinc finger/homeodomain proteins. Like δEF1, SIP1 binds to 5'-CACCT sequences in different promoters, including the Xenopus brachyury promoter. Overexpression of either full-length SIP1 or its C-terminal zinc finger cluster, which bind to the Xbra2 promoter in vitro, prevented expression of the endogenous Xbra gene in early Xenopus embryos. Therefore, SIP1, like δEF1, is likely to be a transcriptional repressor, which may be involved in the regulation of at least one immediate response gene for activin-dependent signal transduction pathways. The identification of this Smad-interacting protein opens new routes to investigate the mechanisms by which transforming growth factor β members exert their effects on expression of target genes in responsive cells and in the vertebrate embryo.

原文英語
頁(從 - 到)20489-20498
頁數10
期刊Journal of Biological Chemistry
274
發行號29
DOIs
出版狀態已發佈 - 1999 七月 16

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學

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