Affinage

LMO4

LIM domain transcription factor LMO4 · UniProt P61968

Length
165 aa
Mass
18.0 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LMO4 is a LIM-only transcriptional adaptor that lacks intrinsic DNA-binding activity but nucleates multi-protein transcription complexes by presenting a tandem-LIM surface that competitively engages partners including Ldb1/CLIM, CtIP, and DEAF1 through a shared binding interface (PMID:15343268, PMID:23353824, PMID:25310299). As a context-dependent co-activator or co-repressor, LMO4 activates NGN2-driven cortical neurogenesis, potentiates PPARγ-mediated neuroprotection, scaffolds JAK1–STAT3 signaling in IL-6 and IL-21 pathways, represses BRCA1 transcriptional activity, and modulates BMP7 expression by displacing HDAC2 from a Clim2 repressor complex (PMID:21652654, PMID:19020036, PMID:39117617, PMID:11751867, PMID:17452977). In the nervous system, LMO4 controls calcium channel gene expression and calcium-induced calcium release critical for synaptic plasticity and learning, governs binary interneuron fate decisions in the spinal cord through LIM-complex switching, and is required for semicircular canal formation and cochlear sensory organ patterning (PMID:22442089, PMID:19323994, PMID:29769265, PMID:25057208). LMO4 is subject to post-translational regulation by peroxynitrite-mediated tyrosine nitration leading to proteasomal degradation and by K48-linked ubiquitination at Lys29/Lys67 catalyzed by the Salmonella effector SsPH2 (PMID:22493493, PMID:40693870).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1998 High

    Identification of LMO4 as a LIM-only protein that binds Ldb1/NLI and DEAF1 established it as a nuclear adaptor assembling multi-protein complexes, answering what molecular partners the newly cloned protein engages.

    Evidence Yeast two-hybrid screens, co-expression studies, domain-mapped interaction with DEAF1 proline-rich region and CLIM LIM-interaction domain

    PMID:9736723 PMID:9840944 PMID:9860983

    Open questions at the time
    • No direct DNA-binding activity tested at this stage
    • Functional consequences of DEAF1 or Ldb1 interaction on transcription not yet addressed
  2. 2001 High

    Discovery that LMO4 forms a quaternary complex with BRCA1, CtIP, and Ldb1 and represses BRCA1-mediated transcription revealed LMO4 can function as a transcriptional co-repressor with tumor-suppressor relevance.

    Evidence Reciprocal co-immunoprecipitation confirming in vivo complex, transcription reporter assays in yeast and mammalian cells

    PMID:11751867

    Open questions at the time
    • Whether LMO4 represses BRCA1 targets in primary tissues unknown
    • Stoichiometry between CtIP and Ldb1 on LMO4 not resolved
  3. 2003 High

    NMR structures of LMO4-LIM1:Ldb1-LID revealed the first atomic-resolution view of LIM-mediated protein-protein interaction, showing Ldb1-LID contributes a β-strand to LMO4's β-hairpin, defining the structural basis for partner recognition.

    Evidence Solution NMR (PDB: 1M3V, 1J2O) of LMO4-LIM1:Ldb1-LID complex

    PMID:12727888

    Open questions at the time
    • Only LIM1 domain resolved; full tandem-LIM:Ldb1 binding mode not yet determined
    • How other partners compete with Ldb1 for this surface unknown
  4. 2004 High

    Crystal structure of full LMO4:Ldb1-LID and knockout mouse studies together established that Ldb1-LID spans both LIM domains and that LMO4 is essential for neural tube closure, linking structural modularity to in vivo developmental function.

    Evidence High-resolution X-ray crystallography with mutagenic validation; homozygous null mice showing exencephaly, proliferation and apoptosis defects

    PMID:14966285 PMID:14966286 PMID:15343268

    Open questions at the time
    • Which transcription factor complexes are disrupted in neural tube closure failure not identified
    • Downstream gene targets in neuroepithelium not mapped
  5. 2005 High

    Transgenic overexpression causing mammary hyperplasia and RNAi knockdown reducing breast cancer cell proliferation/invasion demonstrated that LMO4 levels control mammary epithelial proliferation and motility, establishing oncogenic gain-of-function.

    Evidence MMTV-Lmo4 transgenic mice, siRNA knockdown, migration/invasion assays

    PMID:15897450

    Open questions at the time
    • Direct transcriptional targets mediating mammary phenotype not identified at this point
    • Whether LMO4-driven invasion is BRCA1-dependent or independent unclear
  6. 2006 High

    Multiple studies converged to show LMO4 serves as a signal-responsive scaffolding adaptor: it mediates calcium-dependent transcription via CREB/CLIM complexes in barrel cortex, scaffolds gp130/JAK1/STAT3 in IL-6 signaling, cooperates with GRHL3 in epidermal differentiation, and potentiates TGFβ-Smad signaling.

    Evidence Co-IP of LMO4-CREB-CLIM, conditional cortex KO with barrel defect; yeast two-hybrid/Co-IP for gp130-JAK1; genetic epistasis in double-KO mice for GRHL3; ChIP on PAI-1 promoter for Smad interaction

    PMID:15677447 PMID:16331278 PMID:16899735 PMID:16949565

    Open questions at the time
    • How LMO4 switches between these different signaling complexes (calcium vs. cytokine vs. TGFβ) in a single cell type not resolved
    • Whether gp130 scaffolding and transcription factor co-activation are independent functions unclear
  7. 2007 High

    ChIP-based demonstration that LMO4 and Clim2 occupy the BMP7 promoter and that excess LMO4 displaces HDAC2 from the repressor complex provided the first promoter-level mechanism for LMO4-dependent gene activation in mammary gland.

    Evidence Chromatin immunoprecipitation, conditional mammary KO showing lobuloalveolar defects, reporter assays

    PMID:17452977

    Open questions at the time
    • Whether HDAC2 displacement is a general mechanism at other LMO4-regulated promoters unknown
    • Identity of additional chromatin remodelers in the complex not explored
  8. 2008 High

    LMO4 was shown to be required for inner ear morphogenesis (semicircular canals) and to function as a PPARγ co-activator essential for neuroprotection, extending its roles to sensory organ development and nuclear receptor signaling.

    Evidence Lmo4-null mice lacking semicircular canals with downstream gene expression changes; Co-IP of LMO4-PPARγ, conditional neuronal KO abolishing ischemic neuroprotection

    PMID:19020036 PMID:19913004

    Open questions at the time
    • Whether PPARγ interaction uses the same LIM surface as Ldb1/CtIP not structurally resolved
    • How LMO4 regulates otic morphogen gradients mechanistically unclear
  9. 2009 High

    Genetic epistasis in compound mutant mice demonstrated LMO4 controls the binary V2a/V2b interneuron fate decision by nucleating a novel LIM complex containing SCL, Gata2, and NLI that activates V2b enhancers, establishing the LIM-complex switching paradigm for cell fate.

    Evidence LMO4;SCL compound mutant mice, enhancer reporter assays, complex assembly analysis

    PMID:19323994

    Open questions at the time
    • Whether analogous LIM-complex switching operates in other binary fate decisions (e.g., retina, cortex) not tested
    • Stoichiometry of the SCL-Gata2-NLI-LMO4 complex not determined
  10. 2011 High

    LMO4 was identified as a co-activator of NGN2 recruited to E-box enhancers in cortex and as a cofactor for Snail2-mediated EMT in neural crest, broadening its role to proneural transcription and epithelial-mesenchymal transition.

    Evidence Co-IP/ChIP in cortical neurons with Lmo4-null analysis and in utero electroporation; morpholino knockdown in chick neural crest with direct binding and invasion assays

    PMID:21652654 PMID:23407937

    Open questions at the time
    • Whether LMO4 co-activation of NGN2 requires Ldb1 or is Ldb1-independent not fully dissected
    • Structural basis for Snail2-LMO4 interaction undetermined
  11. 2012 High

    Identification of peroxynitrite-mediated tyrosine nitration as a post-translational modification that destabilizes LMO4 protein without affecting mRNA revealed a non-transcriptional regulatory mechanism, explaining cisplatin-induced cochlear apoptosis.

    Evidence MALDI-TOF mass spectrometry identification of nitrated LMO4, reciprocal IP/IB, LMO4 overexpression rescue of cisplatin cytotoxicity

    PMID:22493493

    Open questions at the time
    • Specific tyrosine residues targeted by nitration not mapped
    • Whether nitration-dependent degradation is proteasome- or autophagy-mediated not determined
  12. 2012 High

    LMO4 was shown to regulate calcium-induced calcium release via RyR2 expression in hippocampal neurons, with forebrain KO impairing LTP and spatial learning, linking LMO4-dependent transcription to synaptic plasticity.

    Evidence Forebrain-specific conditional KO, two-photon calcium imaging, patch-clamp electrophysiology, Morris water maze

    PMID:22442089

    Open questions at the time
    • Whether LMO4 directly occupies the RyR2 promoter not shown by ChIP
    • Upstream signals controlling LMO4 activity in hippocampal plasticity not identified
  13. 2013 High

    NMR structure of LMO4:CtIP revealed that CtIP and Ldb1 bind the same surface on LMO4 in a mutually exclusive manner, establishing a competitive-displacement model that explains how LMO4 overexpression could titrate CtIP away from tumor-suppressive functions.

    Evidence NMR solution structure, competitive binding analysis

    PMID:23353824

    Open questions at the time
    • In vivo stoichiometric measurement of CtIP vs. Ldb1 displacement not performed
    • Whether competitive displacement operates in primary breast tissue unknown
  14. 2014 High

    LMO4 was found to regulate calcium channel genes (Cacna1h, Cacna1e) controlling neuronal excitability in hypothalamic PVH neurons, with PVH-specific deletion causing hyperphagia-induced obesity rescuable by DREADD-mediated excitation, and to suppress ectopic sensory organ formation in the cochlea and reciprocally regulate Lmx1a in inner ear patterning.

    Evidence PVH-specific conditional KO with electrophysiology, qPCR, DREADD rescue; cochlear conditional KO showing ectopic organ of Corti; inner ear double-mutant epistasis

    PMID:24381275 PMID:25057208 PMID:25310299

    Open questions at the time
    • How LMO4 selects specific calcium channel gene promoters versus other targets unknown
    • Whether cochlear sensory competence suppression involves the same LIM-complex switching as spinal cord fate decisions not tested
  15. 2019 High

    Yeats4-dependent H3K27ac reading recruits Dot1l-RNA Pol II to the Lmo4 promoter in common lymphoid progenitors, establishing an epigenetic mechanism for LMO4 transcriptional activation required for innate lymphoid cell lineage commitment.

    Evidence Conditional KO of Yeats4 and Lmo4, ChIP for H3K27ac and Pol II at Lmo4 promoter, ILC differentiation assays

    PMID:31434684

    Open questions at the time
    • Whether Yeats4-Dot1l mechanism operates in non-ILC contexts unknown
    • Downstream LMO4-dependent transcription program in ILC progenitors not characterized
  16. 2024 High

    LMO4 was shown to promote CD8+ T cell stemness and anti-tumor immunity by binding JAK1 and potentiating STAT3 phosphorylation downstream of IL-21, with CRISPR deletion of Stat3 abolishing LMO4-mediated effects, extending the JAK-STAT scaffolding function to adaptive immunity.

    Evidence Co-IP of LMO4-JAK1, STAT3 reporter assays, Stat3 CRISPR KO epistasis, syngeneic and xenograft tumor models

    PMID:39117617

    Open questions at the time
    • Whether LMO4 binds JAK1 via LIM domains or another surface not structurally resolved
    • Mechanism by which LMO4-STAT3 induces Tcf7 and stemness program not fully dissected
  17. 2025 High

    Salmonella effector SsPH2 was shown to target LMO4 for K48-linked ubiquitination at Lys29 and Lys67 within the LIM domains, causing proteasomal degradation and gp130 destabilization that suppresses STAT3 activation, revealing pathogen exploitation of LMO4's scaffolding function.

    Evidence GST pull-down, Co-IP, in vitro and in vivo ubiquitination assays, Lys-to-Arg mutagenesis, immunofluorescence

    PMID:40693870

    Open questions at the time
    • Whether other bacterial effectors or host E3 ligases similarly target LMO4 unknown
    • Impact on LMO4-dependent transcription programs beyond STAT3 not examined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LMO4 selects among its mutually exclusive binding partners (Ldb1, CtIP, DEAF1) in specific cellular contexts, and the post-translational signals governing this switching, remain unresolved.
  • No quantitative in vivo measurement of partner competition dynamics
  • No genome-wide identification of direct LMO4-occupied enhancers across tissues
  • No structural model of LMO4 in complex with JAK1 or PPARγ

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0060090 molecular adaptor activity 5
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-162582 Signal Transduction 5 R-HSA-112316 Neuronal System 3 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 1
Partners
BRCA1CTIP/RBBP8DEAF1GRHL3JAK1LDB1NGN2PPARG
Complex memberships
LMO4-BRCA1-CtIP-Ldb1 complexLMO4-Ldb1/CLIM complexgp130-JAK1-LMO4-STAT3 complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 LMO4 interacts with the nuclear LIM interactor (NLI/Ldb1/CLIM) via its LIM domains, and nuclear retention of LMO4 is enhanced by NLI. LMO4 was identified through its interaction with Ldb1 and is widely expressed in mouse tissues including thymus. Yeast two-hybrid screen, co-expression studies Proceedings of the National Academy of Sciences of the United States of America High 9736723 9840944
1998 LMO4 interacts with the mouse homologue of DEAF-1 (Deformed epidermal autoregulatory factor-1) via a proline-rich C-terminal domain of DEAF-1, distinct from helix-loop-helix and GATA domains; LMO4 also interacts with CLIM coregulators via its LIM domain. Yeast two-hybrid screen, co-immunoprecipitation, library screen using CLIM LIM-interaction domain Proceedings of the National Academy of Sciences of the United States of America High 9860983
2001 LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 via the BRCT domains of BRCA1; a stable in vivo complex comprising LMO4, BRCA1, CtIP, and Ldb1 was demonstrated. LMO4 represses BRCA1-mediated transcriptional activation in both yeast and mammalian cells. Yeast two-hybrid screen, co-immunoprecipitation, functional transcription reporter assays in yeast and mammalian cells The Journal of biological chemistry High 11751867
2001 Forced overexpression of LMO4 inhibits differentiation of mammary epithelial cells in vitro, consistent with a role in maintaining cell proliferation. Forced expression in mammary epithelial cells, differentiation assays Proceedings of the National Academy of Sciences of the United States of America Medium 11734645
2003 LMO4 and LDB1 interact in the nuclear milieu of oral squamous carcinoma cells and co-localize at the invasive front, preferentially in nuclei of less-differentiated carcinoma cells, suggesting a nuclear LMO4-LDB1 transcription complex mediates carcinoma progression. Immunoprecipitation, immunohistochemistry, subcellular localization British journal of cancer Low 12771919
2003 LMO4 interacts with HEN1 (a bHLH protein) and modulates its transcriptional activity; LMO4 (but not LMO2) augments the ability of HEN1 to repress E47-mediated transcriptional activation, and LMO4 prevents HEN1-induced neurite extension in hippocampal precursor cells. Mammalian two-hybrid analysis, reporter gene assays, overexpression in hippocampal precursor cells Biochemical and biophysical research communications Medium 12878195
2003 The solution NMR structures of LMO2-LIM1:ldb1-LID and LMO4-LIM1:ldb1-LID complexes show that ldb1-LID binds to the N-terminal LIM domain of LMO4 in an extended conformation, contributing a third strand to a beta-hairpin; this defines the first molecular basis for LIM-mediated protein-protein interactions. Solution NMR structure determination (PDB: 1M3V and 1J2O) The EMBO journal High 12727888
2004 LMO4 is required for neural tube closure in mice; loss of LMO4 causes failure of anterior neural tube elevation/bending and fusion, exencephaly, abnormal cell proliferation, and elevated apoptosis in neuroepithelium. LMO4 is also required for proper patterning of thalamocortical connections. Homozygous null mutation (gene targeting), histology, BrdU proliferation assay, TUNEL apoptosis assay Molecular and cellular biology High 14966285 14966286 15691703
2004 X-ray crystal structure of LMO4 in complex with Ldb1-LID at high resolution reveals a highly modular structure in which Ldb1-LID binds in an extended manner across both LIM domains of LMO4 with extensive hydrophobic, electrostatic, and backbone-backbone hydrogen bond interactions. Mutagenic screening identified key interface residues. X-ray crystallography (high-resolution), yeast two-hybrid, competition ELISA, site-directed mutagenesis The EMBO journal High 15343268
2005 Overexpression of LMO4 in mouse mammary gland (MMTV-Lmo4 transgene) elicits hyperplasia and mammary intraepithelial neoplasia. siRNA knockdown of LMO4 reduces breast cancer cell proliferation and migration/invasion; conversely, LMO4 overexpression promotes cell motility and invasion in MCF10A cells. Transgenic mouse model, RNAi knockdown, cell migration/invasion assays, cell proliferation assays Proceedings of the National Academy of Sciences of the United States of America High 15897450
2006 LMO4 interacts with the MH1 and linker domains of receptor-mediated Smad proteins and associates with the endogenous TGFβ-responsive PAI-1 gene promoter in a TGFβ-dependent manner, potentiating TGFβ growth-inhibitory signaling in mammary epithelial cells. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), TGFβ-responsive reporter gene assays Oncogene Medium 16331278
2006 LMO4 mediates calcium-dependent transcription in cortical neurons downstream of voltage-sensitive calcium channels and NMDA receptors via CaM kinase IV and MAP kinase signaling. LMO4 forms a complex with CREB, CLIM1, and CLIM2, and conditional cortical deletion of lmo4 disrupts thalamocortical afferent segregation into barrel-specific domains. Co-immunoprecipitation, conditional Cre-Lox knockout mice, neuroanatomical analysis of barrel cortex The Journal of neuroscience : the official journal of the Society for Neuroscience High 16899735
2006 Get-1/Grhl3 interacts functionally with LMO4 in epidermal terminal differentiation; double knockout of Get-1 and LMO4 produces a much more severe differentiation defect than Get-1 single knockout alone, indicating genetic interaction and functional cooperation in stratum corneum formation. Genetic epistasis (double knockout mice), barrier function assays, histology Developmental biology High 16949565
2006 LMO4 associates with gp130 and JAK1 in the IL-6 receptor complex, and also interacts with SHP2 and SOCS3; LMO4 positively regulates STAT3 transcriptional activity and IL-6 signaling, acting as a scaffold to stabilize the gp130 complex. Yeast two-hybrid, in vitro binding assays, co-immunoprecipitation, STAT3 reporter gene assays, siRNA knockdown The Journal of biological chemistry Medium 15677447
2006 LKB1/STK11 forms a complex with LMO4, GATA-6, and Ldb1, enhances GATA-mediated transactivation in a kinase-dependent manner, and induces p21 expression through a p53-independent mechanism in collaboration with this complex. Co-immunoprecipitation, transcriptional reporter assays, kinase-dead mutant analysis Biochemical and biophysical research communications Medium 16580634
2007 LMO4 regulates BMP7 gene expression via an HDAC2-dependent mechanism: LMO4 and Clim2 are recruited to the BMP7 promoter and increased LMO4 levels disrupt the LMO4/Clim2/HDAC2 complex, leading to decreased HDAC2 recruitment and increased BMP7 promoter activity. Conditional deletion of LMO4 in mammary glands impairs lobuloalveolar development. Chromatin immunoprecipitation (ChIP), DNA microarray, conditional knockout mice, BrdU proliferation assay, gene transfer/reporter assays Oncogene High 17452977
2007 Extracellular ATP stabilizes LMO4 mRNA via the 3' UTR; ATP promotes binding of HuD (an RNA-binding protein) to ARE1 in the LMO4 3'UTR, stabilizing the transcript. ATP also destabilizes the CUGBP1 complex at ARE2. This mechanism promotes LMO4 upregulation and neuron survival from hypoxia. Luciferase reporter assays with LMO4 3'UTR, RNA-binding protein pulldown, siRNA knockdown, primary cortical neurons from LMO4 null mice Biochemical and biophysical research communications Medium 17418808
2008 GRHL3 and LMO4 interact biochemically and genetically; double null mice exhibit fully penetrant exencephaly, spina bifida, barrier defect, and eyes-open-at-birth phenotype. LMO4 cooperates with GRHL3 in epidermal migration via ERK1/2 phosphorylation and actin cable formation. Genetic epistasis (double knockout mice), biochemical interaction, electron microscopy, ERK phosphorylation assay, in vitro scratch assay Developmental biology High 18619436
2008 LMO4 is required for semicircular canal and vestibular crista formation; Lmo4-null mice lack three semicircular canals and anterior/posterior cristae due to failed canal outpouching and reduced cell proliferation in the dorsolateral otocyst. LMO4 regulates expression of otic markers Bmp4, Fgf10, Msx1, Isl1, Gata3, and Dlx5. Targeted gene disruption (knockout mice), in situ hybridization, BrdU proliferation assay, gene expression analysis Developmental biology High 19913004
2008 PPARγ signaling requires LMO4 as an essential cofactor for neuroprotection from ischemic injury. LMO4 interacts with PPARγ in a ligand-dependent manner (co-immunoprecipitation and mammalian two-hybrid), augments PPARγ-dependent gene activation by promoting RXRα binding to PPARγ and increasing PPARγ binding to target DNA, and regulates SOD2 promoter activity. LMO4 ablation in neurons abolishes PPARγ agonist-mediated neuroprotection in vitro and in vivo. Co-immunoprecipitation, mammalian two-hybrid, PPARγ reporter assays, conditional knockout mice (CaMKIIα-Cre/LMO4loxP), transient focal ischemia model The Journal of neuroscience : the official journal of the Society for Neuroscience High 19020036
2009 LMO4 controls the binary fate choice between excitatory V2a-interneurons and inhibitory V2b-interneurons in spinal cord by regulating V2a/V2b-specific LIM complexes inversely. LMO4 nucleates a novel LIM complex containing SCL, Gata2, and NLI that activates V2b-specific gene enhancers; in LMO4;SCL compound mutants, V2a interneurons markedly increase at the expense of V2b interneurons. Genetic epistasis (compound mutant mice), enhancer reporter assays, complex assembly analysis Neuron High 19323994
2009 LMO4 is a downstream target of ErbB2 and PI3K in ErbB2-dependent breast cancer cells; LMO4 silencing induces G2/M arrest associated with decreased cullin-3 (E3-ubiquitin ligase component), reduced Cyclin D1 and Cyclin E, and LMO4 expression oscillates throughout the cell cycle with peak at G2/M preceding cullin-3 oscillations. siRNA knockdown, cell cycle analysis by flow cytometry, gene expression profiling, ErbB2/PI3K pathway inhibition Oncogene Medium 19648968
2010 LMO4 silencing in breast cancer cells of multiple subtypes induces G2/M arrest accompanied by centrosome amplification and abnormal mitotic spindle formation; LMO4 overexpression also increases centrosome number, suggesting LMO4 regulates the centrosome cycle. siRNA knockdown, flow cytometry, immunofluorescence microscopy for centrosomes/spindles, overexpression studies The Journal of pathology Medium 20814902
2010 Conditional ablation of LMO4 in retinal progenitor cells results in fewer GABAergic amacrine and OFF-cone bipolar cells (Bhlhb5-positive) in the postnatal retina, with functional deficits in electroretinography b-waves, establishing LMO4 as required for differentiation of inhibitory interneurons in the retina. Conditional knockout mice (Pax6α-Cre/LMO4flox), immunostaining for cell-type markers, electroretinography PloS one High 20949055
2011 LMO4 functions as a co-activator of neurogenin 2 (NGN2) in the developing cortex; LMO4 and NLI/Ldb1 interact with NGN2 simultaneously to form a multi-protein transcription complex recruited to E-box-containing enhancers of NGN2 target genes, activating neurogenin-mediated transcription and facilitating neuronal radial migration. Co-immunoprecipitation, ChIP, reporter assays, Lmo4-null embryo analysis, in utero electroporation Development (Cambridge, England) High 21652654
2011 LMO4 is an essential cofactor in Snail2-mediated cadherin repression and epithelial-to-mesenchymal transition in neural crest cells and neuroblastoma; LMO4 directly binds Slug and Snail, modulates Slug-mediated neural crest induction, and is required for neural crest delamination and neuroblastoma invasion. Morpholino knockdown in chick embryo, direct binding assay, functional EMT assays, invasion assays The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 23407937
2011 LMO4 is expressed in glutamatergic neurons of the hypothalamus; ablation of LMO4 in these neurons impairs leptin-induced fat loss and blunts Stat3 activation in the VMH, while feeding suppression by leptin remains intact, identifying LMO4 as a modulator of selective leptin functions. Conditional knockout mice (glutamatergic-neuron-specific), intracerebroventricular leptin infusion, Stat3 immunostaining, metabolic measurements Cellular and molecular life sciences : CMLS Medium 21874351
2011 Alk is a transcriptional target of LMO4; LMO4 represses Alk transcription in the striatum and LMO4 and ERα are associated with the Alk promoter. ERα knockout increases Alk expression and cocaine sensitization, linking LMO4-ERα-Alk to behavioral responses to cocaine. Chromatin immunoprecipitation, ERα knockout mice, behavioral pharmacology (cocaine sensitization/CPP) The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 21976498
2012 LMO4 positively regulates ryanodine receptor type 2 (RyR2) expression, thereby controlling calcium-induced calcium release (CICR) in hippocampal CA3 neurons. Forebrain-specific LMO4 KO severely compromises CICR modulation of afterhyperpolarization, reduces glutamate release, decreases LTP magnitude, and impairs spatial learning. Forebrain-specific conditional KO mice, two-photon calcium imaging, electrophysiology (patch-clamp, LTP), Morris water maze The Journal of neuroscience : the official journal of the Society for Neuroscience High 22442089
2012 DEAF1 binds to LMO4 via a specific unstructured region that becomes structured upon binding, with the coiled-coil domain containing the DEAF1 nuclear export signal (NES); LMO4 modulates the DEAF1 NES activity, causing nuclear accumulation of the DEAF1 LMO4-interaction region. Yeast two-hybrid, structural domain mapping, NES cell-based localization assay PloS one Medium 22723967
2012 LMO4 is nitrated by peroxynitrite at cochlear proteins following cisplatin treatment; nitration of LMO4 correlates with cisplatin-induced hearing loss, decreases LMO4 protein levels (without corresponding mRNA decrease), and facilitates cochlear apoptosis. Overexpression of LMO4 mitigated cisplatin cytotoxicity. MALDI-TOF mass spectrometry, reciprocal immunoprecipitation/immunoblotting, co-localization immunostaining, LMO4 overexpression The Journal of biological chemistry High 22493493
2013 The solution structure of LMO4 in complex with CtIP/RBBP8 shows that CtIP and Ldb1 bind to the same face on LMO4 and cannot simultaneously bind, suggesting LMO4 overexpression may competitively displace CtIP from normal tumor suppressor activities. NMR solution structure determination, competitive binding analysis Journal of molecular biology High 23353824
2013 HBXIP activates LMO4 transcription through transcription factor Sp1 by binding to the Sp1 binding element in the LMO4 promoter (-237/-206 region); HBXIP-enhanced breast cancer cell proliferation is mediated through upregulation of LMO4 and its downstream effectors cyclin D1 and cyclin E. ChIP assay, EMSA, luciferase reporter with Sp1 site mutagenesis, co-immunoprecipitation, siRNA knockdown, flow cytometry Carcinogenesis Medium 23291272
2014 LMO4 functions as a negative regulator of sensory organ formation in the cochlea; Lmo4 inactivation produces ectopic organ of Corti in the lateral cochlea with mirror-image orientation, revealing LMO4 suppresses sensory competence in this region. Conditional Lmo4 knockout mice, hair cell and supporting cell marker immunostaining, histology The Journal of neuroscience : the official journal of the Society for Neuroscience High 25057208
2014 LMO4 ablation in PVH neurons reduces neuronal excitability and voltage-activated Ca2+ currents; LMO4 regulates expression of Ca2+ channel genes Cacna1h and Cacna1e. PVH-specific LMO4 deletion causes hyperphagia-induced obesity; increasing PVH neuron activity with DREADDs suppresses food intake in LMO4-deficient mice. Conditional knockout mice (PVH-specific), brain slice electrophysiology, real-time PCR, DREADD pharmacogenetics The Journal of neuroscience : the official journal of the Society for Neuroscience High 24381275
2014 Loss of LMO4 in hypothalamic glutamatergic neurons impairs central insulin signaling associated with markedly elevated hypothalamic PTP1B activity; administration of a selective PTP1B inhibitor to the hypothalamus restores central insulin signaling and improves peripheral insulin response. Conditional knockout mice, PTP1B activity assay, intrahypothalamic drug infusion, glucose homeostasis measurement Biochemical and biophysical research communications Medium 24937445
2014 The structure of the LMO4LIM2:DEAF1 complex determined by NMR shows that DEAF1's intrinsically disordered LMO4-binding domain becomes structured upon binding and contacts the same face on LMO4 as LDB1 and CtIP, establishing a common binding mode for LMO4 partners. NMR solution structure, yeast two-hybrid mutagenesis, LMO4LIM2-DEAF1 complex reconstitution PloS one High 25310299
2018 Lmx1a and Lmo4 reciprocally negatively regulate each other in the inner ear; Lmo4 negatively regulates Lmx1a to form the three sensory cristae and anterior semicircular canal, while Lmx1a negatively regulates Lmo4 to mediate epithelial resorption of the canal pouch forming semicircular canals. Conditional knockout mice (inner ear-specific), genetic epistasis (double mutants), in situ hybridization, immunostaining The Journal of neuroscience : the official journal of the Society for Neuroscience High 29769265
2019 Yeats4 recruits the Dot1l-RNA Pol II complex to the Lmo4 promoter through recognition of H3K27ac modification to initiate Lmo4 transcription in α4β7+ CLPs, driving ILC lineage commitment. Lmo4 deficiency also impairs ILC lineage differentiation. Conditional KO mice (Yeats4 and Lmo4), ChIP assay for H3K27ac and Pol II, ILC differentiation assays The Journal of experimental medicine High 31434684
2020 LMO4 in the basolateral amygdala (BLA) regulates alcohol consumption; ChIP revealed LMO4 bound to Oprk1 promoter elements in the BLA; LMO4 transcriptional targets differ dramatically between BLA and nucleus accumbens, explaining divergent phenotypes upon knockdown. ChIP, transcriptome profiling, shRNA knockdown (BLA-specific), behavioral drinking assays Molecular psychiatry Medium 32144357
2024 LMO4 overexpression in CD8+ T cells promotes stemness and tumor rejection by binding to JAK1 and potentiating STAT3 signaling in response to IL-21, inducing target genes (Tcf7, Socs3, Junb, Zfp36) crucial for memory responses; CRISPR deletion of Stat3 abolishes LMO4-mediated effects. Co-immunoprecipitation (LMO4-JAK1), STAT3 reporter assays, CRISPR/Cas9 deletion of Stat3, ectopic LMO4 overexpression, syngeneic/xenograft tumor models Signal transduction and targeted therapy High 39117617
2025 Salmonella effector SsPH2 targets LMO4 for ubiquitination and proteasome-dependent degradation: SsPH2 LRR domain binds LMO4 LIM domains; SsPH2 mediates K48-linked poly-ubiquitination of LMO4 at Lys29 and Lys67 in the LIM domains; SsPH2 alters subcellular localization of LMO4 and destabilizes gp130, inhibiting STAT3 activation. GST pull-down, co-immunoprecipitation, immunofluorescence, in vitro and in vivo ubiquitination assays, site-directed mutagenesis of ubiquitination sites FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 40693870
2012 LMO4 can interact with p53 by co-immunoprecipitation, and p53 transcriptionally represses LMO4 expression; LMO4 inhibits p53-mediated proliferative inhibition of breast cancer cells as shown by colony formation assay. Co-immunoprecipitation, RT-PCR, western blot, colony formation assay Life sciences Low 22906635

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 The Grainyhead-like epithelial transactivator Get-1/Grhl3 regulates epidermal terminal differentiation and interacts functionally with LMO4. Developmental biology 152 16949565
2001 The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity. The Journal of biological chemistry 129 11751867
2001 The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer. Proceedings of the National Academy of Sciences of the United States of America 123 11734645
2004 Defective neural tube closure and anteroposterior patterning in mice lacking the LIM protein LMO4 or its interacting partner Deaf-1. Molecular and cellular biology 104 14966286
2014 Combinatorial expression of Lef1, Lhx2, Lhx5, Lhx9, Lmo3, Lmo4, and Prox1 helps to identify comparable subdivisions in the developing hippocampal formation of mouse and chicken. Frontiers in neuroanatomy 89 25071464
1998 Identification and characterization of LMO4, an LMO gene with a novel pattern of expression during embryogenesis. Proceedings of the National Academy of Sciences of the United States of America 89 9736723
1998 Mouse deformed epidermal autoregulatory factor 1 recruits a LIM domain factor, LMO-4, and CLIM coregulators. Proceedings of the National Academy of Sciences of the United States of America 85 9860983
2004 Tandem LIM domains provide synergistic binding in the LMO4:Ldb1 complex. The EMBO journal 84 15343268
2005 Overexpression of LMO4 induces mammary hyperplasia, promotes cell invasion, and is a predictor of poor outcome in breast cancer. Proceedings of the National Academy of Sciences of the United States of America 79 15897450
2019 Circular RNA circBACH2 plays a role in papillary thyroid carcinoma by sponging miR-139-5p and regulating LMO4 expression. Cell death & disease 75 30796202
2004 Null mutation of the Lmo4 gene or a combined null mutation of the Lmo1/Lmo3 genes causes perinatal lethality, and Lmo4 controls neural tube development in mice. Molecular and cellular biology 75 14966285
2006 Calcium activation of the LMO4 transcription complex and its role in the patterning of thalamocortical connections. The Journal of neuroscience : the official journal of the Society for Neuroscience 71 16899735
2009 LMO4 controls the balance between excitatory and inhibitory spinal V2 interneurons. Neuron 69 19323994
1998 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. Oncogene 65 9840944
2003 Structural basis for the recognition of ldb1 by the N-terminal LIM domains of LMO2 and LMO4. The EMBO journal 61 12727888
2013 The oncoprotein HBXIP activates transcriptional coregulatory protein LMO4 via Sp1 to promote proliferation of breast cancer cells. Carcinogenesis 57 23291272
2007 The LIM-only factor LMO4 regulates expression of the BMP7 gene through an HDAC2-dependent mechanism, and controls cell proliferation and apoptosis of mammary epithelial cells. Oncogene 57 17452977
2009 Lmo4 and Clim1 progressively delineate cortical projection neuron subtypes during development. Cerebral cortex (New York, N.Y. : 1991) 54 19366868
2005 The LIM domain-only protein LMO4 is required for neural tube closure. Molecular and cellular neurosciences 51 15691703
2006 LMO4 can interact with Smad proteins and modulate transforming growth factor-beta signaling in epithelial cells. Oncogene 46 16331278
2015 Cisplatin-induced apoptosis in auditory, renal, and neuronal cells is associated with nitration and downregulation of LMO4. Cell death discovery 44 26925255
2003 The LIM-only protein, LMO4, and the LIM domain-binding protein, LDB1, expression in squamous cell carcinomas of the oral cavity. British journal of cancer 44 12771919
2008 Grhl3 and Lmo4 play coordinate roles in epidermal migration. Developmental biology 43 18619436
2012 LIM domain only 4 (LMO4) regulates calcium-induced calcium release and synaptic plasticity in the hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 42 22442089
2008 Rescue of neurons from ischemic injury by peroxisome proliferator-activated receptor-gamma requires a novel essential cofactor LMO4. The Journal of neuroscience : the official journal of the Society for Neuroscience 42 19020036
2005 Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer. Breast cancer research : BCR 41 16280053
2006 The tumor suppressor LKB1 induces p21 expression in collaboration with LMO4, GATA-6, and Ldb1. Biochemical and biophysical research communications 40 16580634
2003 The LIM-only protein LMO4 modulates the transcriptional activity of HEN1. Biochemical and biophysical research communications 39 12878195
2020 Long non‑coding RNA SNHG1 promotes breast cancer progression by regulation of LMO4. Oncology reports 37 32323846
2012 Cisplatin-induced ototoxicity is mediated by nitroxidative modification of cochlear proteins characterized by nitration of Lmo4. The Journal of biological chemistry 37 22493493
2013 LMO4 is an essential cofactor in the Snail2-mediated epithelial-to-mesenchymal transition of neuroblastoma and neural crest cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 23407937
2007 Extracellular ATP-dependent upregulation of the transcription cofactor LMO4 promotes neuron survival from hypoxia. Experimental cell research 36 17524392
2009 LMO4 is an essential mediator of ErbB2/HER2/Neu-induced breast cancer cell cycle progression. Oncogene 35 19648968
2009 Requirement for Lmo4 in the vestibular morphogenesis of mouse inner ear. Developmental biology 35 19913004
2005 The LIM domain protein Lmo4 is highly expressed in proliferating mouse epithelial tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 35 15805422
2004 Expression of an engrailed-LMO4 fusion protein in mammary epithelial cells inhibits mammary gland development in mice. Oncogene 34 14676840
2005 Modulation of the interleukin-6 receptor subunit glycoprotein 130 complex and its signaling by LMO4 interaction. The Journal of biological chemistry 32 15677447
2011 LMO4 functions as a co-activator of neurogenin 2 in the developing cortex. Development (Cambridge, England) 30 21652654
2002 Differential expression of a transcription regulatory factor, the LIM domain only 4 protein Lmo4, in muscle sensory neurons. Development (Cambridge, England) 29 12397097
2011 Alk is a transcriptional target of LMO4 and ERα that promotes cocaine sensitization and reward. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 21976498
2011 The LIM adaptor protein LMO4 is an essential regulator of neural crest development. Developmental biology 27 22119055
2016 LIM-Only Protein 4 (LMO4) and LIM Domain Binding Protein 1 (LDB1) Promote Growth and Metastasis of Human Head and Neck Cancer (LMO4 and LDB1 in Head and Neck Cancer). PloS one 26 27780223
2010 Lmo4 in the nucleus accumbens regulates cocaine sensitivity. Genes, brain, and behavior 26 20618444
2008 Transcription factor Lmo4 defines the shape of functional areas in developing cortices and regulates sensorimotor control. Developmental biology 25 19111533
2007 LMO4 mRNA stability is regulated by extracellular ATP in F11 cells. Biochemical and biophysical research communications 25 17418808
2005 Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes lobuloalveolar development. Oncogene 25 15856027
2011 Ablation of LMO4 in glutamatergic neurons impairs leptin control of fat metabolism. Cellular and molecular life sciences : CMLS 24 21874351
2004 Differential expression of LMO4 protein in Alzheimer's disease. Neuropathology and applied neurobiology 24 14720177
2020 Circ_0058124 Aggravates the Progression of Papillary Thyroid Carcinoma by Activating LMO4 Expression via Targeting miR-370-3p. Cancer management and research 23 33061633
2014 LMO4 is required to maintain hypothalamic insulin signaling. Biochemical and biophysical research communications 23 24937445
2010 Loss of LMO4 in the retina leads to reduction of GABAergic amacrine cells and functional deficits. PloS one 23 20949055
2003 Transcription regulator LMO4 interferes with neuritogenesis in human SH-SY5Y neuroblastoma cells. Brain research. Molecular brain research 23 12877980
2008 Expression of LMO4 and outcome in pancreatic ductal adenocarcinoma. British journal of cancer 22 18231110
1999 Expression of LMO-4 in the central nervous system of the embryonic and adult mouse. Cellular and molecular biology (Noisy-le-Grand, France) 22 10512198
2014 LMO4 functions as a negative regulator of sensory organ formation in the mammalian cochlea. The Journal of neuroscience : the official journal of the Society for Neuroscience 21 25057208
2012 Contribution of DEAF1 structural domains to the interaction with the breast cancer oncogene LMO4. PloS one 21 22723967
2023 Pro-inflammatory cytokine IL-6 regulates LMO4 expression in psoriatic keratinocytes via AKT/STAT3 pathway. Immunity, inflammation and disease 18 38156380
2019 LMO4 promotes the invasion and proliferation of gastric cancer by activating PI3K-Akt-mTOR signaling. American journal of translational research 18 31737204
2010 Aberrant expression of LMO4 induces centrosome amplification and mitotic spindle abnormalities in breast cancer cells. The Journal of pathology 18 20814902
2018 Reciprocal Negative Regulation Between Lmx1a and Lmo4 Is Required for Inner Ear Formation. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 29769265
2014 Downstream targets of Lmo4 are modulated by cisplatin in the inner ear of Wistar rats. PloS one 17 25501662
2013 BRCA1, LMO4, and CtIP mRNA expression in erlotinib-treated non-small-cell lung cancer patients with EGFR mutations. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 17 23407556
2020 Differential regulation of alcohol consumption and reward by the transcriptional cofactor LMO4. Molecular psychiatry 16 32144357
2019 Yeats4 drives ILC lineage commitment via activation of Lmo4 transcription. The Journal of experimental medicine 16 31434684
2014 LMO4 is essential for paraventricular hypothalamic neuronal activity and calcium channel expression to prevent hyperphagia. The Journal of neuroscience : the official journal of the Society for Neuroscience 16 24381275
2021 CircLDLR Promotes Papillary Thyroid Carcinoma Tumorigenicity by Regulating miR-637/LMO4 Axis. Disease markers 15 34925640
2020 Lmo4-resistin signaling contributes to adipose tissue-liver crosstalk upon weight cycling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 32030835
2017 LMO4 Is a Disease-Provocative Transcription Coregulator Activated by IL-23 in Psoriatic Keratinocytes. The Journal of investigative dermatology 15 29258893
2012 LMO4 inhibits p53-mediated proliferative inhibition of breast cancer cells through interacting p53. Life sciences 15 22906635
2007 A zebrafish LMO4 ortholog limits the size of the forebrain and eyes through negative regulation of six3b and rx3. Developmental biology 15 17692837
2021 Lmo4 Deficiency Enhances Susceptibility to Cisplatin-Induced Cochlear Apoptosis and Hearing Loss. Molecular neurobiology 14 33411315
2012 Lmo4 in the basolateral complex of the amygdala modulates fear learning. PloS one 14 22509321
2021 FOXM1 Promotes Head and Neck Squamous Cell Carcinoma via Activation of the Linc-ROR/LMO4/AKT/PI3K Axis. Frontiers in oncology 13 34447693
2018 LMO4 mediates trastuzumab resistance in HER2 positive breast cancer cells. American journal of cancer research 13 29736306
2003 Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas. International journal of cancer 13 12925972
2024 LIM-domain-only 4 (LMO4) enhances CD8+ T-cell stemness and tumor rejection by boosting IL-21-STAT3 signaling. Signal transduction and targeted therapy 12 39117617
2020 Cisplatin-induced hair cell loss in zebrafish neuromasts is accompanied by protein nitration and Lmo4 degradation. Toxicology and applied pharmacology 12 33245977
2018 miR-150 might inhibit cell proliferation and promote cell apoptosis by targeting LMO4 in Burkitt lymphoma. Journal of cellular physiology 12 30422313
2009 The highly related LIM factors, LMO1, LMO3 and LMO4, play different roles in the regulation of the pituitary glycoprotein hormone alpha-subunit (alpha GSU) gene. Bioscience reports 12 19228115
2003 Two promoters within the human LMO4 gene contribute to its overexpression in breast cancer cells. Genomics 12 12906853
2010 A novel role for transcription factor Lmo4 in thymus development through genetic interaction with Cited2. Developmental dynamics : an official publication of the American Association of Anatomists 11 20549734
2003 Crystallization of FLINC4, an intramolecular LMO4-ldb1 complex. Acta crystallographica. Section D, Biological crystallography 11 12876360
1999 Characterization of the Lmo4 gene encoding a LIM-only protein: genomic organization and comparative chromosomal mapping. Mammalian genome : official journal of the International Mammalian Genome Society 11 10556429
2022 Human umbilical cord mesenchymal stem cell-derived extracellular vesicles carrying miR-655-3p inhibit the development of esophageal cancer by regulating the expression of HIF-1α via a LMO4/HDAC2-dependent mechanism. Cell biology and toxicology 10 36222945
2014 The structure of an LIM-only protein 4 (LMO4) and Deformed epidermal autoregulatory factor-1 (DEAF1) complex reveals a common mode of binding to LMO4. PloS one 10 25310299
2013 LMO4 modulates proliferation and differentiation of 3T3-L1 preadipocytes. FEBS letters 10 23892074
2022 Nimodipine Treatment Protects Auditory Hair Cells from Cisplatin-Induced Cell Death Accompanied by Upregulation of LMO4. International journal of molecular sciences 9 35628594
2013 Structural basis of the interaction of the breast cancer oncogene LMO4 with the tumour suppressor CtIP/RBBP8. Journal of molecular biology 9 23353824
2023 Lmo4 synergizes with Fezf2 to promote direct in vivo reprogramming of upper layer cortical neurons and cortical glia towards deep-layer neuron identities. PLoS biology 8 37552690
2015 A Selective Role for Lmo4 in Cue-Reward Learning. The Journal of neuroscience : the official journal of the Society for Neuroscience 7 26134647
2015 Lmo4 and Other LIM domain only factors are necessary and sufficient for multiple retinal cell type development. Developmental neurobiology 5 26579872
2013 Backbone and side-chain assignments of a tethered complex between LMO4 and DEAF-1. Biomolecular NMR assignments 4 23417771
2011 ¹H, ¹⁵N and ¹³C assignments of an intramolecular LMO4-LIM1/CtIP complex. Biomolecular NMR assignments 4 21643835
2002 Dynamic expression and regulation by Fgf8 and Pou2 of the zebrafish LIM-only gene, lmo4. Mechanisms of development 4 14516683
2002 Dynamic expression and regulation by Fgf8 and Pou2 of the zebrafish LIM-only gene, lmo4. Gene expression patterns : GEP 3 12617802
2025 The Protective Effect of Nimodipine in Schwann Cells Is Related to the Upregulation of LMO4 and SERCA3 Accompanied by the Fine-Tuning of Intracellular Calcium Levels. International journal of molecular sciences 1 39859578
2025 The Type III Secretion Effector SsPH2 of Salmonella enterica Targets LMO4 for Ubiquitination and Degradation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 40693870
2025 miR-143-3p mediates mercury chloride-induced neurotoxicity by targeting LMO4 and the Akt/GSK3β/mTOR pathway in vitro. Toxicological research 1 41503443
2021 Research and Clinical Significance of the Differentially Expressed Genes TP63 and LMO4 in Human Immunodeficiency Virus-Related Penile Squamous Cell Carcinoma. American journal of men's health 1 33906487
2025 LMO4 promotes OSCC progression by inducing RAB17 degradation and ferroptosis resistance. Cell death & disease 0 41213908