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

Research output: Contribution to journalArticle

362 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)20489-20498
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number29
DOIs
Publication statusPublished - 1999 Jul 16

Fingerprint

Smad Proteins
Zinc Fingers
Zinc
Genes
Transforming Growth Factors
Xenopus
Embryonic Structures
Yeast
Homeodomain Proteins
Activins
Two-Hybrid System Techniques
Growth Factor Receptors
Chemical activation
Gene Expression Regulation
Signal transduction
Phosphorylation
Vertebrates
Signal Transduction
Yeasts
Hybrid systems

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Verschueren, K., Remacle, J. E., Collart, C., Kraft, H., Baker, B. S., Tylzanowski, P., ... Huylebroeck, D. (1999). SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5'-CACCT sequences in candidate target genes. Journal of Biological Chemistry, 274(29), 20489-20498. https://doi.org/10.1074/jbc.274.29.20489

SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5'-CACCT sequences in candidate target genes. / Verschueren, Kristin; Remacle, Jacques E.; Collart, Clara; Kraft, Harry; Baker, Betty S.; Tylzanowski, Przemko; Nelles, Luc; Wuytens, Gunther; Su, Ming-Tsan; Bodmer, Rolf; Smith, James C.; Huylebroeck, Danny.

In: Journal of Biological Chemistry, Vol. 274, No. 29, 16.07.1999, p. 20489-20498.

Research output: Contribution to journalArticle

Verschueren, K, Remacle, JE, Collart, C, Kraft, H, Baker, BS, Tylzanowski, P, Nelles, L, Wuytens, G, Su, M-T, Bodmer, R, Smith, JC & Huylebroeck, D 1999, 'SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5'-CACCT sequences in candidate target genes', Journal of Biological Chemistry, vol. 274, no. 29, pp. 20489-20498. https://doi.org/10.1074/jbc.274.29.20489
Verschueren, Kristin ; Remacle, Jacques E. ; Collart, Clara ; Kraft, Harry ; Baker, Betty S. ; Tylzanowski, Przemko ; Nelles, Luc ; Wuytens, Gunther ; Su, Ming-Tsan ; Bodmer, Rolf ; Smith, James C. ; Huylebroeck, Danny. / SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5'-CACCT sequences in candidate target genes. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 29. pp. 20489-20498.
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