Interactions of the LIM-domain-binding factor Ldbl with LIM homeodomain proteins

Abstract

The LIM homeodomain (LIM-HD) proteins, which contain two tandem LIM domains followed by a homeodomain, are critical transcriptional regulators of embryonic development. The LIM domain is a conserved cysteine-rich zinc-binding motif found in LIM-HD and LMO (rhombotin or Ttg) proteins, cytoskeletal components, LIM kinases and other proteins. LIM domains are protein-protein interaction motifs, can inhibit binding of LIM-HD proteins to DNA and can negatively regulate LIM-HD protein function. How LIM domains exert these regulatory effects is not known. We have now isolated a new LIM-domain-binding factor, Ldb1, on the basis of its ability to interact with the LIM-HD protein Lhx1 (Lim1). 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 Ldb protein XLdb1, interacts with Xlim-1, the Xenopus orthologue of Lhx1. When injected into Xenopus embryos, XLdb1 (or Ldb1) can synergize with Xlim-1 in the formation of partial secondary axes and in activation of the genes encoding goosecoid (gsc), chordin, NCAM and XCG7, demonstrating a functional as well as a physical interaction between the two proteins.

Dynamic spatiotemporal expression of LIM genes and cofactors in the embryonic and postnatal cerebral cortex

“…Lhx3,4,6,7,8,Lmx1b, and Isl1, 2 were excluded because previously reported expression patterns reveal their expression to be in only ventral but not dorsal telencephalon, or restricted to nontelencephalic CNS regions, in addition to non-CNS structures (Thor et al, 1991;Li et al, 1994;Tsuchida et al, 1994;Zhadanov et al, 1995;Yamashita et al, 1997;Chen et al, 1998;Grigoriou et al, 1998;Kitanaka et al, 1998). We also included cofactors Clim1a and Clim2 in our study, because their role is closely linked to LIM-HD gene function (Agulnick et al, 1996;Bach et al, 1997;Yamashita et al, 1998).…”

Identification and characterization of Grainyhead‐like epithelial transactivator (GET‐1), a novel mammalian Grainyhead‐like factor

“…Like LIM-HD proteins, LMO factors exhibit nuclear localization, but because these proteins do not bind DNA directly, they must regulate gene transcription by associating with other DNA-binding proteins or coregulators. Several laboratories have isolated highly related and functionally redundant cofactors, referred to as Clim-1 and Clim-2/ Lbd1/NLI, which interact strongly with the LIM domains of LIM-HD proteins (Agulnick et al, 1996;Jurata et al, 1996;Bach et al, 1997;Visvader et al, 1997) and are required for the transactivation function of LIM-HD proteins on enhancers (Bach et al, 1997;Hobert and Westphal, 2000).…”

Identification of the LMO4 gene encoding an interaction partner of the LIM-binding protein LDB1/NLI1: a candidate for displacement by LMO proteins in T cell acute leukaemia

“…The LIM domain can bind to a diverse spectrum of protein motifs, including homodimerization (Sanchez-Garcia et al, 1995), heterodimerization with the basic-helix ± loop ± helix (bHLH) protein TAL1/SCL (Valge-Archer et al, 1994;Wadman et al, 1994), with the GATA-1 DNA-binding protein Wadman et al, 1997) or with the LIM-binding protein LDB1/NLI1 (Agulnick et al, 1996;Bach et al, 1997;Jurata et al, 1996;Wadman et al, 1997). These interactions imply a role for the LMO proteins in control of gene expression by modulation of formation of multimeric protein transcription complexes (Wadman et al, 1997).…”