van Grunsven LA, Michiels C, Van de Putte T, Nelles L, Wuytens G, Verschueren K, Huylebroeck D

Department of Developmental Biology (VIB7), Flanders Interuniversity Institute for Biotechnology (VIB) and Laboratory of Molecular Biology (Celgen), University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.

deltaEF1 and SIP1 (or Zfhx1a and Zfhx1b, respectively) are the only known members of the vertebrate Zfh1 family of homeodomain/zinc finger-containing proteins. Similar to other transcription factors, both Smad-interacting protein-1 (SIP1) and deltaEF1 are capable of repressing E-cadherin transcription through binding to the E2 boxes located in its promoter. In the case of deltaEF1, this repression has been proposed to occur via interaction with the corepressor C-terminal binding protein (CtBP). In this study, we show by coimmunoprecipitation that SIP1 and CtBP interact in vivo and that an isolated CtBP-binding SIP1 fragment depends on CtBP for transcriptional repression. However, and most importantly, full-length SIP1 and deltaEF1 proteins do not depend on their interaction with CtBP to repress transcription from the E-cadherin promoter. Furthermore, in E-cadherin-positive kidney epithelial cells, the conditional synthesis of mutant SIP1 that cannot bind to CtBP abrogates endogenous E-cadherin expression in a similar way as wild-type SIP1. Our results indicate that full-length SIP1 can repress E-cadherin in a CtBP-independent manner.

Mesh Terms:
Alcohol Oxidoreductases, Amino Acid Motifs, Animals, Binding Sites, Blotting, Western, Cadherins, Cell Line, Cells, Cultured, DNA-Binding Proteins, Dogs, Down-Regulation, Gene Expression Regulation, Genes, Reporter, Homeodomain Proteins, Humans, Luciferases, Mice, Microscopy, Fluorescence, Models, Genetic, Mutation, Peptides, Phosphoproteins, Plasmids, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Repressor Proteins, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Two-Hybrid System Techniques, Up-Regulation

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