Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain proteins.
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.
Agulnick
A D
AD
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. agulnica@dir6.nichd.nih.gov
Taira
M
M
Breen
J J
JJ
Tanaka
T
T
Dawid
I B
IB
Westphal
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors; D014981:Xenopus; D029867:Xenopus Proteins
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; C102084:Ldb1 protein, mouse; C543964:Lhx1 protein, Xenopus; C499523:Lhx1 protein, mouse; D011994:Recombinant Proteins; D014157:Transcription Factors; C486314:XLdb1 protein, Xenopus; D029867:Xenopus Proteins