ArticleThe EMBO journal2008
Implementing the LIM code: the structural basis for cell type-specific assembly of LIM-homeodomain complexes.
Article in The EMBO journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 75 citations in OpenAlex.
- Hearing impairment locus heterogeneity and identification of PLS1 as a new autosomal dominant gene in Hungarian Roma.European journal of human genetics : EJHG · 2019Trial
- De novo variants in LDB1 are linked to distinct neurodevelopmental phenotypes determined by variant location and differing pathomechanisms.American journal of human genetics · 2026Article
- Missense mutation of ISL1 (E283D) is associated with the development of type 2 diabetes.Diabetologia · 2024Article
- A global gene regulatory program and its region-specific regulator partition neurons into commissural and ipsilateral projection types.Science advances · 2024Article
- Critical Role of LMCD1 in Promoting Profibrotic Characteristics of Lung Myofibroblasts in Experimental and Scleroderma-Associated Lung Fibrosis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- A BMP4-p38 MAPK signaling axis controls ISL1 protein stability and activity during cardiogenesis.Stem cell reports · 2021Article
- Bioinformatic Analysis of Structure and Function of LIM Domains of Human Zyxin Family Proteins.International journal of molecular sciences · 2021Article
- Contrasting DNA-binding behaviour by ISL1 and LHX3 underpins differential gene targeting in neuronal cell specification.Journal of structural biology: X · 2021Article
- Molecular Aspects of the Development and Function of Auditory Neurons.International journal of molecular sciences · 2020Review
- The islet-expressed Lhx1 transcription factor interacts with Islet-1 and contributes to glucose homeostasis.American journal of physiology. Endocrinology and metabolism · 2019Article
- A variant in LMX1A causes autosomal recessive severe-to-profound hearing impairment.Human genetics · 2018Article
- Disparate binding kinetics by an intrinsically disordered domain enables temporal regulation of transcriptional complex formation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Interactions between LHX3- and ISL1-family LIM-homeodomain transcription factors are conserved in Caenorhabditis elegans.Scientific reports · 2017Article
- Two novel LHX3 mutations in patients with combined pituitary hormone deficiency including cervical rigidity and sensorineural hearing loss.BMC endocrine disorders · 2017Article
- Protein Inhibitor of Activated STAT Y (PIASy) Regulates Insulin Secretion by Interacting with LIM Homeodomain Transcription Factor Isl1.Scientific reports · 2016Article
- The stage-dependent roles of Ldb1 and functional redundancy with Ldb2 in mammalian retinogenesis.Development (Cambridge, England) · 2016Article
- Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice.Molecular neurobiology · 2016Article
- The role of Islet-1 in cell specification, differentiation, and maintenance of phenotypes in the vertebrate neural retina.Neural regeneration research · 2015Article
- Alternative splicing of the LIM-homeodomain transcription factor Isl1 in the mouse retina.Molecular and cellular neurosciences · 2015Article
- Islet-1 Is essential for pancreatic β-cell function.Diabetes · 2014Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
LIM-homeodomain (LIM-HD) transcription factors form a combinatorial 'LIM code' that contributes to the specification of cell types. In the ventral spinal cord, the binary LIM homeobox protein 3 (Lhx3)/LIM domain-binding protein 1 (Ldb1) complex specifies the formation of V2 interneurons. The additional expression of islet-1 (Isl1) in adjacent cells instead specifies the formation of motor neurons through assembly of a ternary complex in which Isl1 contacts both Lhx3 and Ldb1, displacing Lhx3 as the binding partner of Ldb1. However, little is known about how this molecular switch occurs. Here, we have identified the 30-residue Lhx3-binding domain on Isl1 (Isl1(LBD)). Although the LIM interaction domain of Ldb1 (Ldb1(LID)) and Isl1(LBD) share low levels of sequence homology, X-ray and NMR structures reveal that they bind Lhx3 in an identical manner, that is, Isl1(LBD) mimics Ldb1(LID). These data provide a structural basis for the formation of cell type-specific protein-protein interactions in which unstructured linear motifs with diverse sequences compete to bind protein partners. The resulting alternate protein complexes can target different genes to regulate key biological events.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.