Smad-interacting polypeptides and their use

摘要

The current invention concerns SMAD interacting protein(s) obtainable by a two-hybrid screening assay whereby SMAD1 C-domain fused to GAL4 DNA-binding domain as bait and a cDNA library from mouse embryo as prey are used. Some characteristics of a specific SMAD interacting protein (SIP1) of the family of zinc finger/homeodomain proteins including delta-crystallin enhancer binding protein and/or Drosophila zfh-1 include an inability to interact with full size XSMAD1 in yeast, SIP1czf binds to E2 box sites, SIP1czf binds to the Brachyury protein binding site and interferes with Brachyury-mediated transcription activation in cells and also interacts with C-domain of SMAD 1, 2 and 5. The minimal length of the amino acid sequence necessary for binding with SMAD appears to be a 51 amino acid domain encompassing amino acids 166-216 of SEQ ID NO 2 having the amino acid sequence as depicted in the one letter code:QHLGVGMEAPLLGFPTMNSNLSEVQKVLQIVDNTVSRQKMDCKTEDISKLK (SEQ ID NO. 21).