| 1998 |
LMO4 was identified as a binding partner of LDB1/NLI1 via yeast two-hybrid screening; nuclear retention of LMO proteins is enhanced by the nuclear LIM interactor (NLI/LDB1). |
Yeast two-hybrid screen, in situ hybridization |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
9736723
|
| 1998 |
LMO4 interacts strongly with CLIM/LDB coregulators via its LIM domain, and interacts with mouse DEAF-1 (DEFORMED EPIDERMAL AUTOREGULATORY FACTOR 1) through a proline-rich C-terminal domain of DEAF-1, defining a novel LIM-interacting domain distinct from HLH and GATA domains. |
Expression library screen using CLIM LIM-interaction domain as bait; yeast two-hybrid; domain mapping |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
9860983
|
| 1998 |
LMO4 interacts with LDB1/NLI1, and enforced LMO1/LMO2 expression may displace LMO4 from its complex with LDB1 in T cell development. |
Yeast two-hybrid identification of LMO4 via LDB1 interaction |
Oncogene |
Low |
9840944
|
| 2001 |
LMO4 interacts with the cofactor CtIP and with the BRCA1 tumor suppressor (via BRCA1's C-terminal BRCT domains); a stable trimeric complex of LMO4, BRCA1, and CtIP was demonstrated in vivo, and LDB1 also participates. LMO4 represses BRCA1-mediated transcriptional activation in both yeast and mammalian cells. |
Yeast two-hybrid screen, co-immunoprecipitation (in vivo complex), functional transcription reporter assays in yeast and mammalian cells |
The Journal of biological chemistry |
High |
11751867
|
| 2001 |
Forced expression of LMO4 inhibited differentiation of mammary epithelial cells in vitro, consistent with a role in maintaining proliferation. |
Forced expression/overexpression in mammary epithelial cells, differentiation assays |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
11734645
|
| 2003 |
NMR solution 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 in LIM1 domains, providing the first molecular definition of LIM-mediated protein-protein interactions. |
NMR solution structure determination (PDB: 1M3V and 1J2O) |
The EMBO journal |
High |
12727888
|
| 2003 |
LMO4 immunoprecipitates with LDB1 in the nuclear fraction of oral carcinoma cells, confirming formation of an LMO4-LDB1 transcription complex in vivo. |
Co-immunoprecipitation from nuclear fractions of carcinoma cells |
British journal of cancer |
Low |
12771919
|
| 2003 |
LMO4 modulates the transcriptional activity of the bHLH protein HEN1: LMO4 interacts with HEN1 (by mammalian two-hybrid), and LMO4 but not LMO2 augments HEN1-mediated repression of E47 transcription. Overexpression of LMO4 in hippocampal precursor cells prevents HEN1-induced neurite extension. |
Mammalian two-hybrid assay, reporter gene assays, overexpression in hippocampal precursor cells |
Biochemical and biophysical research communications |
Medium |
12878195
|
| 2003 |
Overexpression of LMO4 (sense orientation) reduces neurite number and length in SH-SY5Y neuroblastoma cells, while antisense LMO4 promotes neuritogenesis; LMO4-dependent neuritic effects correlate with altered phosphorylation of cytoskeletal proteins. |
Stable transfection of sense/antisense LMO4 cDNA, morphometric analysis, phosphorylation analysis |
Brain research. Molecular brain research |
Medium |
12877980
|
| 2003 |
A truncating somatic mutation in LMO4 (frameshift at exon 2) generates a LIM1-only mutant that retains LDB1 binding but loses CtIP and BRCA1 association, demonstrating the second LIM domain is required for CtIP/BRCA1 interaction. |
Mutation analysis, binding assays comparing wild-type vs. mutant LMO4 |
International journal of cancer |
Medium |
12925972
|
| 2004 |
X-ray crystal structure of LMO4 in complex with LDB1-LID (the FLINC4 complex) at high resolution reveals a highly modular structure with Ldb1-LID binding in an extended manner across both LIM domains of LMO4, with extensive hydrophobic and electrostatic interactions. Mutagenic screening of Ldb1-LID (yeast two-hybrid and competition ELISA) identified key interface residues. |
X-ray crystallography (high-resolution crystal structure), mutagenic screen assessed by yeast two-hybrid and competition ELISA |
The EMBO journal |
High |
15343268
|
| 2004 |
Lmo4-null mice die perinatally and show severe neural tube defect (exencephaly/anencephaly); conditional null demonstrates LMO4 is required for proper closure of the anterior neural tube, with loss causing abnormal cell proliferation and elevated apoptosis in the neuroepithelium. LMO4 is expressed in neuroepithelial cells and Schwann cell progenitors. |
Gene targeting (null mutation), histology, BrdU proliferation assay, TUNEL apoptosis assay |
Molecular and cellular biology / Molecular and cellular neurosciences |
High |
14966285 15691703
|
| 2004 |
The transcription factor Deaf-1/NUDR is a binding partner of LMO4 in vivo; Deaf-1 knockout mice share overlapping phenotypes with Lmo4 knockouts (exencephaly, vertebral homeotic transformations), indicating they act in a functional complex. |
Gene targeting of both Lmo4 and Deaf-1 in mice, phenotypic comparison (genetic epistasis) |
Molecular and cellular biology |
High |
14966286
|
| 2005 |
LMO4 overexpression in the mouse mammary gland (MMTV-Lmo4 transgene) elicits hyperplasia and mammary intraepithelial neoplasia; siRNA knockdown of LMO4 reduces proliferation of breast cancer cells and increases differentiation of mammary epithelial cells; LMO4 overexpression in MCF10A cells promotes cell motility and invasion of extracellular matrix. |
Transgenic mouse model (MMTV-Lmo4), siRNA knockdown, Matrigel invasion assay, cell motility assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
15897450
|
| 2005 |
Conditional deletion of Lmo4 in mammary epithelium during pregnancy impairs lobuloalveolar development with a 2-fold reduction in BrdU-positive proliferating cells, demonstrating LMO4 is a positive regulator of alveolar epithelial proliferation. |
Conditional knockout (Cre-lox), BrdU incorporation, mammary gland histology |
Oncogene |
High |
15856027
|
| 2006 |
LMO4 mediates calcium-dependent transcription in cortical neurons: calcium influx via VSCCs and NMDA receptors activates LMO4-mediated transactivation via CaM kinase IV and MAP kinase. LMO4 forms a complex with CREB, CLIM1, and CLIM2 (by co-immunoprecipitation). Conditional cortical deletion of Lmo4 disrupts barrel field segregation of thalamocortical afferents in somatosensory cortex. |
Luciferase reporter assay (calcium stimulation), pharmacological inhibitors, co-immunoprecipitation, conditional Cre-lox knockout, barrel field histology |
The Journal of neuroscience |
High |
16899735
|
| 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; LMO4 modulates TGFβ signaling in epithelial cells and potentiates growth-inhibitory effects of TGFβ. |
Co-immunoprecipitation (LMO4-Smad interaction), chromatin immunoprecipitation (LMO4 at PAI-1 promoter), TGFβ-responsive reporter gene assays |
Oncogene |
Medium |
16331278
|
| 2006 |
Get-1/Grhl3 and LMO4 interact functionally (genetically) in epidermal terminal differentiation: double knockout of Get-1 and LMO4 causes more severe stratum corneum defects than Get-1 single knockout alone. |
Compound knockout mouse model (Get-1−/−; LMO4−/−), epidermal barrier assays, histology |
Developmental biology |
Medium |
16949565
|
| 2007 |
LMO4 regulates expression of BMP7 by a mechanism involving displacement of HDAC2 from the BMP7 promoter: LMO4 and its cofactor Clim2 are recruited to the BMP7 promoter (ChIP), HDAC2 recruitment is inhibited by LMO4 upregulation, and HDAC2 knockdown upregulates the promoter. Inhibition of BMP7 partially blocks LMO4-mediated effects on apoptosis. |
DNA microarray, promoter-reporter assay, chromatin immunoprecipitation (LMO4, Clim2, HDAC2 at BMP7 promoter), siRNA knockdown |
Oncogene |
High |
17452977
|
| 2007 |
LMO4 is a downstream effector of ATP signaling that promotes neuron survival from hypoxia; extracellular ATP stabilizes LMO4 mRNA via the ARE1 element in the 3'UTR by increasing HuD protein binding, while CUGBP1 binds sequences flanking ARE2 and is destabilized by ATP. ERK and CREB activation by ATP increases LMO4 promoter activity and LMO4 protein stability. |
siRNA knockdown, luciferase 3'UTR reporter, RNA-binding protein assays (HuD/CUGBP1), primary LMO4-null neurons |
Experimental cell research / Biochemical and biophysical research communications |
Medium |
17418808 17524392
|
| 2008 |
GRHL3 and LMO4 interact biochemically and genetically; compound Grhl3/Lmo4 null mice show fully penetrant exencephaly, spina bifida, and eyes-open-at-birth phenotype not seen in individual nulls. ERK1/2 phosphorylation is lost in the epidermis of double-null embryos, actin cable formation is absent at eyelid margins, and keratinocytes from double-null mice fail to heal in scratch assays. |
Compound knockout mouse model, biochemical interaction assay, electron microscopy, phospho-ERK immunostaining, in vitro scratch assay |
Developmental biology |
High |
18619436
|
| 2008 |
LMO4 is required for vestibular morphogenesis: Lmo4-null mice lack all three semicircular canals and anterior/posterior cristae; canal outpouches fail to form and cell proliferation is reduced in the dorsolateral otocyst. LMO4 controls expression of Bmp4, Fgf10, Msx1, Isl1, Gata3, and Dlx5 in the dorsolateral otocyst. |
Gene targeting (null mutation), BrdU proliferation assay, in situ hybridization for otic markers |
Developmental biology |
High |
19913004
|
| 2005 |
LMO4 associates with gp130 and JAK1 in mammalian cells; it also interacts with SHP2 and SOCS3, and exists in the gp130 IL-6 receptor complex. LMO4 overexpression enhances STAT3 transcriptional activity and target gene expression, while LMO4 siRNA knockdown decreases STAT3 activity. LMO4 is detected both in the nucleus and cytoplasm. |
Yeast two-hybrid screen, in vitro binding assays, co-immunoprecipitation, siRNA stable knockdown, reporter assay |
The Journal of biological chemistry |
Medium |
15677447
|
| 2006 |
LKB1 forms a complex with LMO4, GATA-6, and Ldb1, enhancing GATA-mediated transactivation in a kinase-dependent manner; this complex induces p21 expression via a p53-independent mechanism. |
Co-immunoprecipitation (complex formation), reporter gene assay (GATA-mediated transactivation, p21 promoter), kinase-dead mutant |
Biochemical and biophysical research communications |
Medium |
16580634
|
| 2008 |
PPARγ signaling requires LMO4 as an essential cofactor to protect neurons from ischemic injury: LMO4 interacts with PPARγ in a ligand-dependent manner (co-immunoprecipitation, mammalian two-hybrid), promotes RXRα binding to PPARγ, increases PPARγ binding to target DNA, and activates SOD2 promoter. PPARγ agonist failed to reduce cerebral infarction in neuron-specific LMO4-null mice. |
Co-immunoprecipitation, mammalian two-hybrid, LMO4-null cortical neurons, conditional forebrain knockout (CaMKIIα-Cre/LMO4loxP), focal ischemia model, promoter reporter assay, MnTBAP rescue |
The Journal of neuroscience |
High |
19020036
|
| 2009 |
LMO4 controls the binary fate choice between excitatory V2a and inhibitory V2b spinal interneurons by regulating LIM complexes: LMO4 induces GABAergic V2b interneurons in collaboration with SCL and inhibits Lhx3 from generating glutamatergic V2a interneurons. LMO4 nucleates assembly of a novel LIM-complex containing SCL, Gata2, and NLI, which activates V2b-specific enhancers. In LMO4;SCL compound mutants, V2a cells increase at the expense of V2b cells. |
Conditional knockout, compound mutant (LMO4;SCL), enhancer reporter assay, co-immunoprecipitation (complex assembly), in situ hybridization for V2a/V2b markers |
Neuron |
High |
19323994
|
| 2009 |
LMO4 is a downstream target of ErbB2 and PI3K signaling in breast cancer cells; LMO4 silencing causes G2/M arrest associated with decreased cullin-3 (E3 ubiquitin ligase component), followed by reductions in Cyclin D1 and Cyclin E. LMO4 expression oscillates through the cell cycle with maximum at G2/M, preceding cullin-3 oscillations. |
Gene expression profiling, siRNA knockdown, cell cycle analysis (FACS), immunoblotting, PI3K inhibitor treatment |
Oncogene |
Medium |
19648968
|
| 2011 |
LMO4 functions as a co-activator of Neurogenin 2 (NGN2) in the developing cortex: LMO4 and NLI/LDB1 interact with NGN2 simultaneously, forming a multi-protein transcription complex recruited to E-box-containing enhancers of NGN2-target genes. Loss of LMO4 in Lmo4-null embryos impairs neuronal differentiation, and LMO4 expression facilitates NGN2-mediated radial migration of cortical neurons. |
Co-immunoprecipitation (LMO4-NLI-NGN2 complex), chromatin immunoprecipitation (complex at NGN2-target enhancers), Lmo4-null embryo analysis, in utero electroporation (migration assay) |
Development |
High |
21652654
|
| 2011 |
LMO4 is a Slug/Snail interacting protein (direct binding demonstrated); LMO4 morpholino knockdown in Xenopus causes loss of neural crest precursor formation, and misexpression of LMO4 modulates Slug-mediated neural crest induction, indicating LMO4 is an essential cofactor in Snail2-mediated neural crest development. |
Morpholino knockdown (Xenopus), misexpression, co-immunoprecipitation/direct binding assay for LMO4-Slug/Snail interaction |
Developmental biology |
Medium |
22119055
|
| 2011 |
LMO4 is repressed by Alk transcription in the striatum; LMO4 and ERα are associated with the Alk promoter (chromatin immunoprecipitation), and Alk is an estrogen-responsive gene modulated by LMO4 in the striatum. ERα knockout mice show enhanced cocaine sensitization and increased Alk expression. |
Chromatin immunoprecipitation (LMO4 and ERα at Alk promoter), ERα knockout, RNA interference in striatum |
The Journal of neuroscience |
Medium |
21976498
|
| 2012 |
LMO4 positively regulates ryanodine receptor type 2 (RyR2) expression; forebrain-specific LMO4 knockout neurons have severely compromised calcium-induced calcium release (CICR) modulation of afterhyperpolarization (rescued by single-cell LMO4 overexpression), absent caffeine-potentiated RyR-mediated calcium release, defective CICR-facilitated glutamate release, and reduced CA3-CA1 LTP. |
Conditional forebrain knockout, electrophysiology (patch clamp), two-photon calcium imaging, single-cell overexpression rescue, Morris water maze |
The Journal of neuroscience |
High |
22442089
|
| 2012 |
LMO4 interacts with p53 (co-immunoprecipitation) and inhibits p53-mediated suppression of breast cancer cell colony formation; p53 induction by adriamycin represses LMO4 expression, indicating LMO4 is a transcriptional target of p53. |
Co-immunoprecipitation, colony formation assay, RT-PCR/Western blot after ADR treatment |
Life sciences |
Low |
22906635
|
| 2012 |
LMO4 nitration at tyrosine residues in the cochlea is the primary molecular event in cisplatin-induced ototoxicity: cisplatin induces nitroxidative protein modification and nitration of LMO4 (identified by MALDI-TOF mass spectrometry, confirmed by reciprocal immunoprecipitation and immunoblotting), leading to decreased cochlear LMO4 levels and cochlear apoptosis. |
MALDI-TOF mass spectrometry, reciprocal co-immunoprecipitation/immunoblotting, immunofluorescence co-localization of nitrotyrosine and LMO4, in vitro nitration assay |
The Journal of biological chemistry |
High |
22493493
|
| 2012 |
LMO4 is required for normal DEAF1 nuclear export: LMO4 modulates the activity of the DEAF1 nuclear export signal (NES) within a coiled-coil domain, causing nuclear accumulation of constructs containing the LMO4-interaction region of DEAF1. The specific LMO4-binding domain in DEAF1 contains an unstructured region that directly contacts LMO4. |
Yeast two-hybrid domain mapping, cell-based NES activity assay, co-expression/localization |
PloS one |
Medium |
22723967
|
| 2013 |
LMO4 is an essential cofactor in Snail2-mediated epithelial-to-mesenchymal transition and cadherin repression in neuroblastoma and neural crest cells; LMO4 knockdown impairs neuroblastoma cell invasion and neural crest delamination, and LMO4 is required for Snail2-mediated cadherin downregulation. |
siRNA/shRNA knockdown, invasion assay, in vivo chick neural crest delamination assay, cadherin expression analysis |
The Journal of neuroscience |
Medium |
23407937
|
| 2013 |
HBXIP activates LMO4 transcription by binding to the LMO4 promoter through the transcription factor Sp1 at the −237/−206 region; HBXIP co-immunoprecipitates with Sp1, ChIP shows HBXIP at the LMO4 promoter, and mutation of the Sp1 site abolishes HBXIP-LMO4 promoter interaction. |
Co-immunoprecipitation, chromatin immunoprecipitation, electrophoretic mobility shift assay, luciferase reporter, Sp1-binding site mutagenesis |
Carcinogenesis |
Medium |
23291272
|
| 2013 |
The solution NMR structure of LMO4 in complex with CtIP/RBBP8 reveals that CtIP and LDB1 bind to the same face on LMO4 and cannot simultaneously bind LMO4, suggesting competitive binding between these two partners. |
NMR solution structure determination, competition binding assay |
Journal of molecular biology |
High |
23353824
|
| 2014 |
Loss of LMO4 in retinal progenitor cells leads to fewer Bhlhb5-positive GABAergic amacrine and OFF-cone bipolar cells (affecting the postnatal wave), with functional deficit shown by reduced b-wave amplitude on electroretinography; cholinergic/dopaminergic amacrine, rod bipolar, and photoreceptor cell numbers are not affected. |
Conditional knockout (Pax6α-Cre/LMO4flox), cell counting by immunostaining, electroretinography |
PloS one |
High |
20949055
|
| 2014 |
The NMR solution structure of the LMO4-LIM2/DEAF1 complex shows that DEAF1's intrinsically disordered LMO4-binding domain becomes structured upon binding LMO4, and DEAF1 binds the same face on LMO4 as LDB1 and CtIP; mutagenic screening identified key residues in LMO4-LIM2 and the N-terminal half of DEAF1's binding domain. |
NMR solution structure, yeast two-hybrid mutagenic screening, domain mapping |
PloS one |
High |
25310299
|
| 2014 |
LMO4 inactivation in the cochlea causes ectopic formation of an organ of Corti (eOC) in the lateral cochlea with inner/outer hair cells and supporting cells but in mirror-image orientation, demonstrating LMO4 is a negative regulator of sensory organ formation in the cochlea. |
Conditional knockout (Lmo4 inactivation), histology, hair cell markers (immunostaining) |
The Journal of neuroscience |
High |
25057208
|
| 2014 |
LMO4 regulates the expression of Ca2+ channel subunits Cacna1h and Cacna1e in PVH neurons; PVH-specific LMO4 ablation reduces voltage-activated Ca2+ currents and basal neuronal excitability, leading to hyperphagia. Restoring neuronal activity by DREADD technology suppresses food intake in these mice. |
Conditional (PVH-specific) knockout, brain slice electrophysiology (patch clamp for Ca2+ currents), real-time PCR for Ca2+ channel expression, DREADD designer receptor |
The Journal of neuroscience |
High |
24381275
|
| 2014 |
Loss of LMO4 in hypothalamic glutamatergic neurons impairs insulin signaling in the hypothalamus and peripheral tissues (liver, skeletal muscle), associated with markedly elevated PTP1B activity; administration of a PTP1B inhibitor to the hypothalamus restores insulin signaling and improves peripheral insulin response in LMO4-deficient mice. |
Conditional knockout (glutamatergic neuron-specific), insulin signaling assays (phospho-IR, phospho-Akt), PTP1B activity assay, intracerebroventricular drug delivery |
Biochemical and biophysical research communications |
Medium |
24937445
|
| 2015 |
LMO4 is required for cisplatin-induced cochlear apoptosis: hair cell-specific Lmo4 conditional knockout mice show elevated auditory brainstem response thresholds after cisplatin; LMO4 deficiency compromises STAT3 phosphorylation (anti-apoptotic) and increases activated caspase-3 in hair cells post-cisplatin. |
Conditional knockout (Lmo4lox/lox; Gfi1Cre), auditory brainstem response, immunostaining for phospho-STAT3 and caspase-3 |
Molecular neurobiology |
High |
33411315
|
| 2015 |
LMO4 in the basolateral amygdala (BLA) is required for cue-reward learning but not fear learning or anxiety; knockdown of LMO4 in BLA (but not nucleus accumbens) impairs conditioned reinforcement; molecular analysis identifies a deficit in dopamine D2 receptor signaling in the BLA of Lmo4-deficient mice. |
Lmo4-deficient mice, BLA-specific RNA interference, conditioned reinforcement behavioral assay, electrophysiology (D2 receptor signaling) |
The Journal of neuroscience |
Medium |
26134647
|
| 2015 |
Cisplatin treatment modulates LMO4's downstream cochlear interactome: Esr1 (estrogen receptor 1) is upregulated and Stat3 is downregulated by cisplatin in the cochlea; Trolox co-treatment attenuates these effects, and immunoblots confirm cisplatin-induced decrease in cochlear STAT3 protein is attenuated by Trolox, suggesting LMO4 loss promotes STAT3 repression in cisplatin ototoxicity. |
Custom gene array, RT-PCR, immunoblotting (STAT3), antioxidant rescue (Trolox co-treatment) in rats |
PloS one |
Low |
25501662
|
| 2018 |
Lmx1a and Lmo4 mutually negatively regulate each other in the inner ear: Lmo4 negatively regulates Lmx1a to allow formation of the three sensory cristae and blocks ectopic cochlear sensory formation; Lmx1a negatively regulates Lmo4 to mediate epithelial resorption of the canal pouch. Conditional knockout of Lmx1a shows the inner ear source is the major contributor to ear patterning. |
Conditional knockout of Lmx1a and compound mutant analysis with Lmo4; histology, in situ hybridization for otic markers |
The Journal of neuroscience |
High |
29769265
|
| 2019 |
Yeats4 recruits the Dot1l-RNA Pol II complex onto the Lmo4 promoter by recognizing H3K27ac modification, initiating Lmo4 transcription in α4β7+ CLPs; Yeats4 conditional KO decreases ILC numbers and Lmo4 expression, and Lmo4 deficiency also impairs ILC lineage differentiation. |
Conditional knockout, ChIP (Yeats4, Dot1l, RNA Pol II at Lmo4 promoter), H3K27ac recognition assay |
The Journal of experimental medicine |
Medium |
31434684
|
| 2020 |
LMO4 binds the Oprk1 promoter (chromatin immunoprecipitation) in the basolateral amygdala (BLA), regulating kappa opioid receptor expression; LMO4 also controls extracellular matrix gene expression in the BLA. BLA-specific Lmo4 knockdown decreases alcohol consumption; disruption of ECM or kappa opioid receptor antagonism in the BLA reduces alcohol consumption. |
Lmo4 heterozygous and shRNA knockdown, RNA-seq, chromatin immunoprecipitation, pharmacological dissection (BLA infusion) |
Molecular psychiatry |
Medium |
32144357
|
| 2021 |
Lmo4 deficiency enhances susceptibility to cisplatin-induced cochlear apoptosis: hair cell-specific conditional LMO4 deletion does not alter baseline cochlear morphology or hearing but significantly increases ABR thresholds after cisplatin; LMO4 deficiency impairs STAT3 activation, and this LMO4/STAT3 axis is an otoprotective cellular defense mechanism. |
Conditional knockout (Lmo4lox/lox; Gfi1Cre), ABR, immunostaining (phospho-STAT3, caspase-3) |
Molecular neurobiology |
High |
33411315
|
| 2024 |
LMO4 binds JAK1 directly and potentiates STAT3 signaling in response to IL-21 in CD8+ T cells, inducing expression of stemness-related target genes (Tcf7, Socs3, Junb, Zfp36). CRISPR/Cas9 deletion of STAT3 nullifies the enhanced memory signature conferred by LMO4. LMO4 overexpression in CD8+ T cells promotes stem-like memory phenotype and antitumor immunity. |
CRISPR activation screen, synthetic overexpression, co-immunoprecipitation (LMO4-JAK1 interaction), CRISPR/Cas9 Stat3 deletion, syngeneic and xenograft tumor models, transcriptomics |
Signal transduction and targeted therapy |
High |
39117617
|
| 2025 |
Salmonella effector SsPH2 targets LMO4 for ubiquitination and proteasome-dependent degradation: SsPH2 mediates K48-linked poly-ubiquitination of LMO4 at Lysine 29 and Lysine 67 within the LIM domains (in vivo and in vitro); SsPH2 alters the subcellular localization of LMO4, destabilizes gp130, and inhibits STAT3 activation. |
Yeast two-hybrid screen, GST pull-down, co-immunoprecipitation, immunofluorescence microscopy, in vitro and in vivo ubiquitination assay, lysine mutational analysis, proteasome inhibitor rescue |
FASEB journal |
High |
40693870
|
| 2025 |
LMO4 promotes OSCC progression by inducing ubiquitin-proteasome-dependent degradation of the tumor suppressor RAB17, thereby promoting cancer cell proliferation, migration, and resistance to ferroptosis; restoration of RAB17 reduces these malignant behaviors and reduces in vivo tumor growth. |
siRNA/overexpression, ubiquitin-proteasome pathway assay, xenograft model, immunostaining for RAB17 and LMO4 |
Cell death & disease |
Medium |
41213908
|