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 so-called SIP1 are the follwing: a) it fails to interact with full size XSmad1 in yeast; b) it is a member of the family of zinc finger/homeodomain proteins including delta -crystallin enhancer binding protein and/or Drosophila zfh-1; c) SIP1czf binds to E2 box sites; d) SIP1czf binds to the Brachyury protein binding site; e) it interferes with Brachyury-mediated transcription activation in cells and f) it 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 aa domain encompassing aa 166-216 of SEQ ID NO 2 having the amino acid sequence as depicted in the one letter code: QHLGVGMEAPLLGFPTMNSNLSEVQKVLQIVDNTVSRQKMDCKTEDISKLK.