INTERACTIONS OF THE LIM-DOMAIN-BINDING FACTOR LDB1 WITH LIM HOMEODOMAIN PROTEINS

THE LIM homeodomain (LIM-HD) proteins, which contain two tandem LIM do mains followed by a homeodomain, are critical transcriptional regulato rs of embryonic development(1-5). The LIM domain is a conserved cystei ne-rich zinc-binding motif found in LIM-HD and LMO (rhombotin or Ttg) proteins, cytoskeletal components, LIM kinases and other proteins(1). LIM domains are protein-protein interaction motifs(1), can binding of LIM-HD proteins to DNA(6,7) and can negatively regulate LIM-HD protein function(8). How LIM domains exert these regulatory effects is not kn own. We have now isolated a new LIM-domain-binding factor, LdB1, on th e basis of tis ability to interact with the LIM-HD protein Lhx1 (Lim1) (9). High-affinity binding by Ldb1 requires paired LIM domains and is restricted to the related subgroup of LIM domains found in LIM-HD and LMO proteins. The highly conserved Xenopus Lbd protein XLbd1, interact s with Xlim-1, the Xenopus orthologue of Lhx1. When injected into Xeno pus embryos, XLbd1 (or Lbd1) can synergize with Xlim-1 in the formatio n of partial secondary axes and in activation of the genes encoding go osecoid (gsc), chordin, NCAM and XCG7, demonstrating a functional as w ell as a physical interaction between the two proteins.