Affinage

LIMA1

LIM domain and actin-binding protein 1 · UniProt Q9UHB6

Length
759 aa
Mass
85.2 kDa
Annotated
2026-04-28
57 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIMA1 (EPLIN) is a cytoskeletal scaffolding protein that stabilizes actin filaments, links cadherin–catenin adhesion complexes to the cortical actin network, and bridges membrane transporters to motor-driven trafficking machinery. It directly binds and cross-links F-actin through two actin-binding sites, inhibits Arp2/3-mediated branched nucleation, and is recruited to adherens junctions via alpha-catenin in a tension-dependent manner, where it maintains the circumferential actin belt and cooperates with vinculin to preserve zonula adherens integrity (PMID:12566430, PMID:18093941, PMID:21844208). LIMA1 stability and localization are tightly controlled by ERK-mediated phosphorylation (reducing actin affinity), O-GlcNAcylation at T662 (blocking ubiquitin-dependent degradation), and multiple E3 ubiquitin ligase pathways including Rab40b–Cullin5, RNF40, and STUB1, which target it for proteasomal turnover to regulate focal adhesion dynamics, cell migration, and lipid metabolism (PMID:17875928, PMID:33999101, PMID:39921472, PMID:38909032). In the intestinal brush border, LIMA1 bridges the cholesterol transporter NPC1L1 to a myosin Vb transport complex, and Lima1-deficient mice are resistant to diet-induced hypercholesterolemia; a human frameshift variant in LIMA1 is linked to reduced cholesterol absorption (PMID:29880681).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1999 Medium

    Establishing LIMA1 as a novel LIM-domain cytoskeletal protein with two isoforms answered whether the gene encoded a structural or signaling factor, placing it at actin filaments with growth-suppressive properties.

    Evidence Immunofluorescence localization to F-actin and overexpression proliferation assay in epithelial cells

    PMID:10618726

    Open questions at the time
    • Mechanism of proliferation suppression unknown
    • No biochemical actin-binding data yet
  2. 2002 Medium

    Mapping the N-terminal region as essential for both actin localization and anchorage-independent growth suppression established that cytoskeletal targeting is required for LIMA1's tumor-suppressive function.

    Evidence Truncated EPLIN constructs in NIH3T3 cells with soft-agar colony formation and immunofluorescence

    PMID:11950948

    Open questions at the time
    • Specific actin-binding domains not yet biochemically defined
    • No in vivo tumor model
  3. 2003 High

    Reconstitution with purified protein demonstrated that LIMA1 directly binds, bundles, and stabilizes actin filaments while inhibiting Arp2/3-mediated branching, defining its core biochemical activities.

    Evidence In vitro depolymerization, bundling, and Arp2/3 nucleation assays with purified recombinant EPLIN

    PMID:12566430

    Open questions at the time
    • Relative contribution of the two actin-binding sites in cells unknown
    • No structural model of actin–EPLIN interface
  4. 2007 High

    Discovery that ERK phosphorylates LIMA1 at C-terminal serines to reduce actin affinity, redistribute LIMA1 to ruffles, and enable PDGF-induced migration revealed the first post-translational switch controlling LIMA1 function.

    Evidence In vitro ERK kinase assay, phospho-site mutagenesis, wound healing assay with PDGF stimulation

    PMID:17875928

    Open questions at the time
    • No crystal structure of phosphorylated vs. unphosphorylated actin-binding domain
    • Whether other kinases target the same sites not tested
  5. 2007 High

    Identification of LIMA1 as the physical link between alpha-catenin and F-actin at adherens junctions resolved a long-standing question of how the cadherin–catenin complex engages the actin cytoskeleton.

    Evidence Reciprocal Co-IP of EPLIN with alpha-catenin; siRNA depletion converting circumferential actin belt to radial zipper junctions in epithelial cells

    PMID:18093941

    Open questions at the time
    • Whether the interaction is direct or via additional adaptor proteins at endogenous stoichiometry
    • Mechanosensitivity not yet tested
  6. 2009 Medium

    Localization of LIMA1 to the cleavage furrow via myosin II and septin interactions, and multinucleation upon depletion, extended LIMA1 function beyond junctions to cytokinesis.

    Evidence Co-IP with myosin II and Sept2; siRNA depletion with multinucleation quantification

    PMID:19221476

    Open questions at the time
    • Whether LIMA1 is required for contractile ring assembly or maintenance not distinguished
    • No live imaging of furrow dynamics after depletion
  7. 2010 Medium

    Demonstrating that MAL/MRTF–SRF signaling transcriptionally induces only EPLIN-alpha revealed isoform-specific transcriptional regulation linked to the cellular actin monomer/polymer balance.

    Evidence MAL/SRF ChIP at EPLIN-alpha promoter; dominant-negative MAL and actin-binding drugs

    PMID:20236507

    Open questions at the time
    • Transcriptional regulation of EPLIN-beta isoform not identified
    • In vivo relevance not tested
  8. 2011 High

    Multiple groups established that junctional tension retains LIMA1 at adherens junctions and that LIMA1 cooperates with vinculin to maintain zonula adherens integrity, defining it as a mechanosensitive junction regulator in both epithelial and endothelial cells.

    Evidence Alpha-catenin–EPLIN fusion rescue; mechanical perturbation and live imaging; GST pulldown and Co-IP in endothelial cells with Matrigel tube formation

    PMID:21625216 PMID:21844208 PMID:22194609

    Open questions at the time
    • Force range required for LIMA1 retention not quantified
    • Whether catch-bond or slip-bond mechanism applies unknown
  9. 2012 High

    Showing that EGF triggers ERK-dependent phosphorylation, ubiquitination, and proteasomal degradation of LIMA1 unified the phosphorylation and turnover pathways into a single growth-factor-regulated degradation cascade.

    Evidence Phospho-site mutagenesis conferring resistance to EGF-induced turnover; ubiquitination assay; cycloheximide chase in prostate cancer cells

    PMID:23188829

    Open questions at the time
    • E3 ligase responsible for phosphorylation-triggered ubiquitination not identified in this study
  10. 2015 High

    Three contemporaneous studies expanded LIMA1's functional repertoire: API2-MALT1 paracaspase cleaves LIMA1 to generate an oncogenic LIM fragment in MALT lymphoma, LIMA1 interacts with PINCH-1 at focal adhesions to control keratinocyte spreading, and LIMA1 promotes apical extrusion of transformed cells.

    Evidence Paracaspase cleavage assay with active-site mutant controls validated in primary tumors; PINCH-1 interactome by MS with conditional KO; mixed culture extrusion assay with epistasis

    PMID:25569716 PMID:25609703 PMID:25609711

    Open questions at the time
    • Whether the oncogenic LIM fragment acts through a gain-of-function binding partner or dominant-negative mechanism is unclear
    • How PINCH-1 recruits LIMA1 structurally is unknown
  11. 2018 High

    Identification of LIMA1 as a bridge between NPC1L1 and myosin Vb in the intestinal brush border, with Lima1 KO mice showing reduced cholesterol absorption, established a non-cytoskeletal physiological role in cholesterol metabolism validated by human genetic data.

    Evidence Human frameshift variant; Lima1 KO mouse with cholesterol absorption measurements; Co-IP of LIMA1 with NPC1L1 and myosin Vb

    PMID:29880681

    Open questions at the time
    • Whether LIMA1 actively participates in vesicle motility or serves as a passive scaffold is unresolved
    • Stoichiometry of the NPC1L1–LIMA1–myosin Vb complex unknown
  12. 2019 High

    FRAP and isoform-specific analysis demonstrated that EPLIN-alpha terminates Arp2/3-driven branching at protrusions while EPLIN-beta stabilizes stress fibers with slower turnover, functionally distinguishing the two isoforms at the subcellular level.

    Evidence Isoform-specific overexpression/depletion; FRAP dynamics; co-localization with Arp2/3 in endothelial cells under shear

    PMID:31644899

    Open questions at the time
    • Whether the N-terminal extension of EPLIN-beta mediates its preferential stress fiber association is not mapped
    • In vivo isoform-specific functions not tested
  13. 2020 Medium

    Discovery that LIMA1 interacts with LUZP1 to restrict ciliogenesis by mobilizing ARP2 to centrosomes and limiting MyosinVa accumulation linked LIMA1 to centrosome biology and primary cilium regulation.

    Evidence BioID proximity proteomics; siRNA depletion increasing cilia formation; centrosome MyosinVa immunofluorescence

    PMID:32496561

    Open questions at the time
    • Whether LIMA1 directly binds centrosomal structures or acts indirectly through actin is unclear
    • In vivo ciliogenesis phenotype not examined
  14. 2021 High

    Identification of Rab40b–Cullin5 as an E3 complex that locally ubiquitinates and degrades LIMA1 at focal adhesions established a spatially restricted degradation mechanism controlling adhesion dynamics and invadopodia formation.

    Evidence Co-IP of Rab40b with Cullin5 and EPLIN; direct ubiquitylation assay; interaction mutants; migration and invasion rescue

    PMID:33999101

    Open questions at the time
    • Whether Rab40b–Cullin5 targets a specific LIMA1 isoform preferentially is unknown
    • Ubiquitination sites on LIMA1 not mapped
  15. 2022 Medium

    In pluripotent stem cells, Lima1 expression controlled by the naive pluripotency circuit suppresses membrane blebbing and supports mitochondrial energetics, revealing a developmental context for LIMA1 function beyond epithelial junctions.

    Evidence Lima1 KO and forced expression in mouse ESCs; live imaging; mitochondrial respiration assay; chimera assay

    PMID:35105859

    Open questions at the time
    • Mechanism by which LIMA1 influences mitochondrial energetics is unexplained
    • Whether this reflects direct or indirect actin-dependent effect unknown
  16. 2023 Medium

    Two studies revealed additional layers of LIMA1 turnover control: Az1/OAZ1 degrades EPLIN-beta in a ubiquitin-independent, proteasome-dependent manner, while USP44 deubiquitinates LIMA1 and its nuclear sequestration by MAD2 promotes LIMA1 K48-ubiquitination.

    Evidence Quantitative proteomics identifying EPLIN-beta as Az1 substrate with Co-IP; USP44–LIMA1 Co-IP with K48-ubiquitination assay and nuclear fractionation

    PMID:37325974 PMID:37752233

    Open questions at the time
    • Whether Az1 and ubiquitin-dependent pathways compete or act on distinct pools is unknown
    • Identity of the E3 ligase in the MAD2/USP44 axis not established
  17. 2024 High

    Multiple 2024 studies identified new LIMA1 regulatory inputs and partners: O-GlcNAcylation at T662 stabilizes LIMA1 to promote hepatic steatosis via β-catenin/FASn, RNF40 ubiquitinates LIMA1 to reduce lipid content, SEPT9 binds the LIM domain to regulate filopodia, and p62 stabilizes LIMA1 protein levels.

    Evidence O-GlcNAc site mapping by MS with T662A knock-in mice; RNF40 Co-IP with domain mapping and ubiquitination assay; SEPT9 KO fibroblasts with EPLIN rescue; GST pulldown of p62 with EPLIN

    PMID:38185251 PMID:38719752 PMID:38909032 PMID:39921472

    Open questions at the time
    • Interplay among the multiple E3 ligases (Rab40b-Cul5, RNF40, STUB1) targeting LIMA1 is not clarified
    • Structural basis of O-GlcNAc protection from ubiquitination unknown
  18. 2025 Medium

    LIMA1 forms a ternary complex with IRBIT and the Cl⁻/HCO₃⁻ exchanger SLC26A3 at the brush border, and LIMA1 knockdown selectively impairs cAMP/ATP-stimulated DRA transport activity, extending LIMA1's scaffolding role to intestinal ion transport regulation.

    Evidence Co-IP of DRA with IRBIT and LIMA1; siRNA knockdown; functional SLC26A3 transport assay in intestinal cells

    PMID:40569378

    Open questions at the time
    • Whether LIMA1 binds DRA or IRBIT directly vs. through actin is unresolved
    • In vivo ion transport phenotype in Lima1 KO intestine not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of LIMA1's isoform-specific functions, how multiple E3 ligases and the Az1 pathway are coordinated to achieve spatiotemporal control of LIMA1 levels, and whether LIMA1's roles in cholesterol absorption, ciliogenesis, and junction remodeling converge on a unified actin-scaffolding mechanism.
  • No high-resolution structure of LIMA1 bound to actin or alpha-catenin
  • Isoform-specific knockout mice not generated
  • Integration of O-GlcNAcylation, ERK phosphorylation, and multiple ubiquitin ligase pathways in a single model system not achieved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0060090 molecular adaptor activity 4 GO:0005198 structural molecule activity 3
Localization
GO:0005856 cytoskeleton 5 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-162582 Signal Transduction 5 R-HSA-1500931 Cell-Cell communication 4 R-HSA-1430728 Metabolism 2 R-HSA-382551 Transport of small molecules 2 R-HSA-1640170 Cell Cycle 1
Partners
CTNNA1LUZP1MYO5BNPC1L1PINCH1RNF40SEPT2SEPT9
Complex memberships
E-cadherin–catenin–EPLIN junctional complexNPC1L1–LIMA1–myosin Vb transport complexRab40b–Cullin5 ubiquitin ligase complex (as substrate)

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 EPLIN directly binds actin filaments at two distinct binding sites, inhibits actin filament depolymerization, cross-links filaments into bundles, and inhibits branching nucleation by the Arp2/3 complex via side-binding activity; it does not affect spontaneous polymerization kinetics or barbed-end elongation. In vitro biochemical assays with purified recombinant EPLIN (depolymerization assay, bundling/cross-linking assay, Arp2/3-mediated nucleation assay, actin polymerization kinetics) The Journal of cell biology High 12566430
1999 EPLIN is a cytoskeletal protein with a single central LIM domain that localizes to filamentous actin and suppresses cell proliferation when overexpressed; two isoforms (alpha, 600 aa; beta, 759 aa) are generated from a single gene. Subcellular localization by immunofluorescence; overexpression in epithelial cells with proliferation assay Oncogene Medium 10618726
2002 The N-terminal region of EPLIN is required for both its localization to the actin cytoskeleton and suppression of anchorage-independent growth; loss of cytoskeletal localization (as in Ras-transformed cells) abolishes the tumor-suppressive function. Retroviral transduction of truncated EPLIN constructs in NIH3T3 cells; soft-agar colony formation assay; immunofluorescence localization Molecular biology of the cell Medium 11950948
2007 ERK phosphorylates EPLIN at Ser360, Ser602, and Ser692; phosphorylation of the C-terminal region reduces EPLIN's affinity for actin filaments. ERK-mediated phosphorylation drives redistribution of EPLIN from stress fibers to membrane ruffles and is required for PDGF-induced stress fiber disassembly, membrane ruffling, and cell migration. In vitro kinase assay with purified ERK and EPLIN; phospho-specific antibodies in intact cells; non-phosphorylatable mutant overexpression; wound healing and migration assays; PDGF stimulation Molecular and cellular biology High 17875928
2007 EPLIN (LIMA1) couples with alpha-catenin and links the E-cadherin–catenin complex to F-actin at adherens junctions. EPLIN depletion disorganizes the circumferential actin adhesion belt, converting it to zipper-like junctions with radially arranged actin, without affecting non-junctional actin fibers. Co-immunoprecipitation of EPLIN with alpha-catenin; siRNA depletion in epithelial cells; immunofluorescence of actin and junctional markers Proceedings of the National Academy of Sciences of the United States of America High 18093941
2009 EPLIN localizes to the cleavage furrow during cytokinesis via association with contractile ring components myosin II and the septin Sept2; EPLIN depletion causes multinucleation due to inefficient accumulation of active myosin II (MRLC-S19), Sept2, RhoA, and Cdc42 at the furrow. Immunofluorescence localization during cytokinesis; Co-immunoprecipitation with myosin II and Sept2; siRNA depletion with multinucleation quantification Cell cycle Medium 19221476
2011 Junctional tension is required to retain EPLIN at adherens junctions; lateral actin fiber forces inhibit EPLIN–AJ association. An alpha-catenin–EPLIN fusion promotes zonula adherens (ZA) formation but not punctate AJ formation, placing EPLIN as a mechanosensitive regulator downstream of tension at the ZA. Vinculin cooperates with EPLIN to maintain ZA integrity. Live imaging of EPLIN at junctions with mechanical perturbation; rescue experiments with alpha-catenin–EPLIN fusion construct; vinculin depletion combined with EPLIN depletion The Journal of cell biology High 21844208
2011 EPLIN interacts directly with alpha-catenin and tethers the VE-cadherin–catenin complex to the actin cytoskeleton in endothelial cells; EPLIN depletion delocalizes vinculin from junctions and reduces pseudocapillary network formation in a Matrigel angiogenesis assay. Co-immunoprecipitation and GST pulldown of EPLIN with alpha-catenin; siRNA depletion; immunofluorescence; Matrigel tube formation assay; blebbistatin treatment The Journal of biological chemistry High 22194609
2011 EPLIN depletion during epithelial-mesenchymal transition in prostate cancer cells causes disassembly of adherens junctions, actin remodeling, and activation of beta-catenin signaling, establishing EPLIN as a negative regulator of EMT. siRNA depletion; immunofluorescence of junctional markers; beta-catenin reporter assay; quantitative proteomics in EMT model Oncogene Medium 21625216
2012 EGF promotes ERK1/2-dependent phosphorylation, ubiquitination, and proteasomal degradation of EPLIN; Ser362 and Ser604 are the critical ERK1/2 phosphorylation sites whose mutation confers resistance to EGF-induced EPLIN turnover. EGF stimulation of prostate cancer cells; ERK1/2 inhibitor treatment; phospho-site mutagenesis; ubiquitination assay; cycloheximide chase The Journal of biological chemistry High 23188829
2013 DNp73 drives loss of EPLIN expression, which de-represses IGF1R signaling and activates AKT/STAT3 to promote migration and invasion; EPLIN acts as a direct inhibitor of IGF1R-AKT/STAT3 activation downstream of the p73/DNp73 axis. Knockdown/overexpression of DNp73 and EPLIN; xenograft invasion/metastasis assay; signaling pathway analysis by Western blot; co-expression rescue experiments Cancer cell Medium 24135282
2015 API2-MALT1 fusion protein cleaves LIMA1 via MALT1 paracaspase activity; API2 mediates LIMA1 binding, and proteolysis generates an oncogenic LIM-domain-only fragment that promotes lymphomagenesis. Primary MALT lymphomas harboring API2-MALT1 uniquely show LIMA1 cleavage fragments. Co-immunoprecipitation; paracaspase cleavage assay with API2-MALT1 mutants; in vitro and in vivo oncogenicity assays; primary tumor immunoblot for cleavage products Nature communications High 25569716
2015 EPLIN functions upstream of Caveolin-1 in RasV12-transformed cells surrounded by normal cells, promoting apical extrusion; EPLIN regulates non-cell-autonomous myosin-II and PKA activation in transformed cells and affects filamin A accumulation in neighboring normal cells. siRNA depletion; mixed culture of normal and RasV12-transformed cells; live imaging of apical extrusion; epistasis experiments (EPLIN KD upstream of Cav-1 KD) Journal of cell science Medium 25609711
2015 PINCH-1 interacts with EPLIN at integrin adhesion sites in keratinocytes; EPLIN localization to focal adhesions is PINCH-1-dependent; EPLIN depletion severely attenuates keratinocyte spreading and migration on collagen and fibronectin independently of PINCH-1 levels. PINCH-1 interactome by mass spectrometry; co-immunoprecipitation; PINCH-1 conditional knockout in epidermis; EPLIN siRNA depletion; adhesion and migration assays Journal of cell science High 25609703
2017 p53 transcriptionally induces LIMA1 expression by binding two p53 response elements in the LIMA1 gene; LIMA1 mediates p53-dependent suppression of cancer cell invasion. ChIP-seq for p53 binding; microarray identification of LIMA1 as p53 target; nutlin-3a activation of endogenous p53; LIMA1 knockdown in p53 invasion-suppression assay Cancer letters Medium 28093207
2018 LIMA1 is expressed in the small intestinal brush border membrane and bridges NPC1L1 (the cholesterol transporter) to a myosin Vb-containing transport complex, facilitating intestinal cholesterol uptake. Lima1-deficient mice show reduced cholesterol absorption and resistance to diet-induced hypercholesterolemia. Rare frameshift variant identification in family; Lima1 KO mouse model; brush border fractionation; co-immunoprecipitation of LIMA1 with NPC1L1 and myosin Vb; cholesterol absorption measurements Science High 29880681
2018 Paxillin binds EPLIN specifically in RasV12-transformed cells surrounded by normal cells; paxillin, plectin, and EPLIN mutually influence their accumulation and cooperate to promote acetylated tubulin enrichment via paxillin-mediated suppression of HDAC6, facilitating apical extrusion. Co-immunoprecipitation of paxillin with EPLIN in mixed culture; siRNA depletion; immunofluorescence of acetylated tubulin and HDAC6 activity assay Scientific reports Medium 29391412
2010 EPLIN-alpha transcription is regulated by the actin-MAL/MRTF-SRF signaling pathway; monomeric actin represses MAL-SRF-dependent EPLIN-alpha expression, while conditions that release MAL from G-actin induce EPLIN-alpha but not EPLIN-beta, revealing isoform-specific transcriptional control. Transcriptome analysis with actin-binding drugs; dominant-negative MAL overexpression; constitutively active actin mutants; MAL/SRF ChIP at EPLIN-alpha promoter; promoter-reporter assays Molecular cancer Medium 20236507
2019 EPLIN-alpha localizes to membrane protrusions and interacts with the Arp2/3 complex to terminate branched actin growth, while EPLIN-beta localizes to stress fibers and stabilizes them; FRAP shows lower EPLIN-beta turnover rate, consistent with a filament-stabilizing role distinct from EPLIN-alpha's protrusion-regulating function. Isoform-specific overexpression and depletion; FRAP of EPLIN-alpha vs. -beta; co-localization with Arp2/3; shear stress experiments in aortic vs. vena cava endothelial cells Cell reports High 31644899
2020 EPLIN interacts with LUZP1 and together they restrict primary cilia formation; depleting either EPLIN or LUZP1 increases MyosinVa at the centrosome and promotes ciliogenesis. EPLIN and LUZP1 stabilize actin dynamics at least partly by mobilizing ARP2 to centrosomes. Proximity ligation/BioID interactome; siRNA depletion of EPLIN or LUZP1; cilia quantification; centrosome MyosinVa immunofluorescence; actin dynamics assays The Journal of cell biology Medium 32496561
2021 Rab40b interacts with Cullin5 via its SOCS domain and EPLIN is a binding partner and substrate for Rab40b-Cullin5-dependent localized ubiquitylation and degradation; loss of this ubiquitylation increases EPLIN levels, stabilizes focal adhesions, and reduces cell migration and invadopodia formation. Co-immunoprecipitation of Rab40b with Cullin5 and EPLIN; ubiquitylation assay; Rab40b-Cullin5 interaction mutants; EPLIN degradation rescue experiments; migration and invasion assays The Journal of cell biology High 33999101
2022 Lima1 expression is controlled by the naive pluripotency circuit in mouse embryonic stem cells and is required to suppress membrane blebbing and maintain proper mitochondrial energetics; forced Lima1 expression enables primed pluripotent cells to incorporate into pre-implantation embryos. Lima1 KO and overexpression in mouse ESCs; live imaging of membrane blebbing; mitochondrial respiration assay; chimera assay in pre-implantation embryos Nature communications Medium 35105859
2022 LIMA1 inhibits the Wnt/beta-catenin pathway in hepatocellular carcinoma by binding BMI1 and inducing its destabilization; loss of LIMA1 stabilizes BMI1 and activates beta-catenin signaling to promote HCC proliferation and metastasis. Co-immunoprecipitation of LIMA1 with BMI1; overexpression/knockdown of LIMA1; beta-catenin reporter assay; xenograft mouse model Cells Medium 36497115
2023 EPLIN-beta (but not EPLIN-alpha) is a novel substrate of ornithine decarboxylase antizyme 1 (Az1/OAZ1); Az1 degrades EPLIN-beta in a ubiquitination-independent, proteasome-mediated manner; Az1 absence elevates EPLIN-beta and causes enhanced cellular migration. Quantitative proteomics to identify Az1 substrates; co-immunoprecipitation of EPLIN-beta with Az1; ubiquitination assay (showing independence); proteasome inhibitor rescue; migration assay after Az1 KO Journal of cell science Medium 37325974
2023 MAD2 sequesters USP44 in the nucleus, preventing USP44 from binding and deubiquitinating LIMA1, leading to enhanced K48-linked ubiquitination and degradation of LIMA1 and consequent activation of IGF1R/PI3K/AKT signaling in cholangiocarcinoma. Co-immunoprecipitation of USP44 with LIMA1; ubiquitination assay (K48-linked); nuclear fractionation showing MAD2 sequestration of USP44; pathway activation by Western blot; PDTX model Oncogene Medium 37752233
2024 RNF40, an E3 ubiquitin ligase, mediates ubiquitination and proteasomal degradation of LIMA1; the 1–166 aa fragment of LIMA1 is indispensable for the LIMA1–RNF40 interaction. RNF40-mediated LIMA1 degradation reduces cellular lipid content, which is reversed by LIMA1 overexpression. Co-immunoprecipitation of RNF40 with LIMA1; domain-mapping with truncation mutants; ubiquitination assay; proteasome inhibitor rescue; lipid content measurement Cell death discovery Medium 38909032
2024 Cytoplasmic p62 (SQSTM1) interacts with EPLIN via GST pulldown and enhances EPLIN protein stability; elevated EPLIN in ESCC promotes migration and invasion, and reducing EPLIN expression inhibits these phenotypes. GST pulldown of p62 with EPLIN; p62 knockdown/overexpression with localization control; EPLIN rescue after p62 KD; migration and invasion assays Experimental cell research Medium 38185251
2024 LIMA1 O-GlcNAcylation at T662 (catalyzed by OGT, promoted by steatosis-induced HCF1/OGT upregulation) inhibits its ubiquitin-dependent degradation and enhances hepatocyte lipid deposition via activation of beta-catenin/FASn signaling; LIMA1-T662A mutant mice showed reduced steatosis, inflammation, and fibrosis. O-GlcNAc site mapping by mass spectrometry; site-directed mutagenesis (T662A); AAV-mediated liver-specific expression in LIMA1 HKO mice; beta-catenin/FASn pathway analysis by Western blot; OGT inhibitor studies Advanced science High 39921472
2024 LIMA1 interacts with PINK1 and inhibits PINK1-Parkin-mediated mitophagy in hepatic stellate cells; LIMA1 delivered via lipotoxic hepatocyte-derived small extracellular vesicles promotes HSC activation by blocking mitophagy. Molecular docking and database prediction; LIMA1 KD in LX2 cells; mt-keima lentivirus to detect mitophagy; sEV isolation and delivery assay; in vivo HFD mouse model Cellular & molecular biology letters Low 38822260
2024 SEPT9 directly interacts with the LIM domain of EPLIN; this interaction regulates actin stress fiber and filopodia organization, focal adhesion size, and cell adhesion and migration in human fibroblasts. Increased EPLIN levels can partially rescue the low motility of SEPT9 KO cells. SEPT9 KO fibroblast cell line; co-expression and interaction assays; immunofluorescence of actin structures and focal adhesions; migration assays with rescue by EPLIN overexpression Life science alliance Medium 38719752
2025 IRBIT and LIMA1 form a complex with the brush border Cl-/HCO3- exchanger SLC26A3 (DRA); cAMP/ATP stimulation increases the association of LIMA1 with both IRBIT and DRA; LIMA1 knockdown selectively reduces cAMP plus ATP stimulation of DRA activity without affecting basal activity. Co-immunoprecipitation of DRA with IRBIT and LIMA1; LIMA1 siRNA knockdown; functional SLC26A3 transport assay with pharmacological stimulation; brush border fractionation American journal of physiology. Cell physiology Medium 40569378
2026 BPNT1 recruits E3 ubiquitin ligase STUB1 to induce proteasomal degradation of LIMA1, promoting EMT and TNBC progression; re-expression of LIMA1 in BPNT1-overexpressing cells partially reverses EMT and malignant phenotypes. Co-immunoprecipitation of BPNT1 with STUB1 and LIMA1; ubiquitination/degradation assay; LIMA1 re-expression rescue; xenograft mouse model; in vitro invasion/migration assays Cell death & disease Medium 41540000
2024 EPLINα localizes to Rab21-positive recycling endosomes (in addition to actin ruffles) via its actin-binding activity; EPLINα interacts with Rab21 and supports beta1-integrin recycling and cell migration. Coronin 1C is an EPLIN-proximal protein at Rab21 endosomes in an EPLINα-dependent manner. High EPLINα-to-EPLINβ ratio correlates with mesenchymal phenotype in breast cancer. Isoform-specific localization by live imaging; BioID proximity proteomics; Co-localization of EPLINα with Rab21 and F-actin on endosomes; actin-binding mutant; integrin recycling assay bioRxivpreprint Medium bio_10.1101_2024.06.27.600789

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 EPLIN mediates linkage of the cadherin catenin complex to F-actin and stabilizes the circumferential actin belt. Proceedings of the National Academy of Sciences of the United States of America 319 18093941
2003 EPLIN regulates actin dynamics by cross-linking and stabilizing filaments. The Journal of cell biology 141 12566430
2011 Mechanosensitive EPLIN-dependent remodeling of adherens junctions regulates epithelial reshaping. The Journal of cell biology 131 21844208
2018 A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption. Science (New York, N.Y.) 118 29880681
2008 Eplin-alpha expression in human breast cancer, the impact on cellular migration and clinical outcome. Molecular cancer 102 18796137
2013 DNp73 exerts function in metastasis initiation by disconnecting the inhibitory role of EPLIN on IGF1R-AKT/STAT3 signaling. Cancer cell 86 24135282
1999 EPLIN, epithelial protein lost in neoplasm. Oncogene 83 10618726
2015 EPLIN is a crucial regulator for extrusion of RasV12-transformed cells. Journal of cell science 70 25609711
2011 EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis. Oncogene 70 21625216
2007 Extracellular signal-regulated kinase/mitogen-activated protein kinase regulates actin organization and cell motility by phosphorylating the actin cross-linking protein EPLIN. Molecular and cellular biology 65 17875928
2011 Epithelial protein lost in neoplasm (EPLIN) interacts with α-catenin and actin filaments in endothelial cells and stabilizes vascular capillary network in vitro. The Journal of biological chemistry 60 22194609
2015 Conversion of the LIMA1 tumour suppressor into an oncogenic LMO-like protein by API2-MALT1 in MALT lymphoma. Nature communications 50 25569716
2012 Epidermal growth factor promotes protein degradation of epithelial protein lost in neoplasm (EPLIN), a putative metastasis suppressor, during epithelial-mesenchymal transition. The Journal of biological chemistry 42 23188829
2002 Inhibition of anchorage-independent growth of transformed NIH3T3 cells by epithelial protein lost in neoplasm (EPLIN) requires localization of EPLIN to actin cytoskeleton. Molecular biology of the cell 42 11950948
2022 CAF-Released Exosomal miR-20a-5p Facilitates HCC Progression via the LIMA1-Mediated β-Catenin Pathway. Cells 39 36497115
2017 MiR-93-5p enhances growth and angiogenesis capacity of HUVECs by down-regulating EPLIN. Oncotarget 36 29291009
2000 Characterization of the human EPLIN (Epithelial Protein Lost in Neoplasm) gene reveals distinct promoters for the two EPLIN isoforms. Gene 36 10806352
2017 p53 mediates the suppression of cancer cell invasion by inducing LIMA1/EPLIN. Cancer letters 35 28093207
2015 EPLIN: a fundamental actin regulator in cancer metastasis? Cancer metastasis reviews 35 26350886
2019 EPLIN-α and -β Isoforms Modulate Endothelial Cell Dynamics through a Spatiotemporally Differentiated Interaction with Actin. Cell reports 32 31644899
2009 The actin-binding and bundling protein, EPLIN, is required for cytokinesis. Cell cycle (Georgetown, Tex.) 32 19221476
2020 LUZP1 and the tumor suppressor EPLIN modulate actin stability to restrict primary cilia formation. The Journal of cell biology 28 32496561
2018 The paxillin-plectin-EPLIN complex promotes apical elimination of RasV12-transformed cells by modulating HDAC6-regulated tubulin acetylation. Scientific reports 25 29391412
2015 The focal adhesion protein PINCH-1 associates with EPLIN at integrin adhesion sites. Journal of cell science 25 25609703
2012 EPLIN-α expression in human oesophageal cancer and its impact on cellular aggressiveness and clinical outcome. Anticancer research 24 22493360
2022 Lima1 mediates the pluripotency control of membrane dynamics and cellular metabolism. Nature communications 22 35105859
2011 EPLIN is a negative regulator of prostate cancer growth and invasion. The Journal of urology 22 21600601
2021 Rab40-Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration. The Journal of cell biology 21 33999101
2024 Lipotoxic hepatocyte derived LIMA1 enriched small extracellular vesicles promote hepatic stellate cells activation via inhibiting mitophagy. Cellular & molecular biology letters 18 38822260
2023 Characterization of LIMA1 and its emerging roles and potential therapeutic prospects in cancers. Frontiers in oncology 18 37274282
2017 Epithelial protein lost in neoplasm (EPLIN): Beyond a tumor suppressor. Genes & diseases 18 30258911
2021 Epithelial Protein Lost in Neoplasm, EPLIN, the Cellular and Molecular Prospects in Cancers. Biomolecules 17 34356662
2001 Characterization of mouse epithelial protein lost in neoplasm (EPLIN) and comparison of mammalian and zebrafish EPLIN. Gene 17 11179679
2023 MAD2 activates IGF1R/PI3K/AKT pathway and promotes cholangiocarcinoma progression by interfering USP44/LIMA1 complex. Oncogene 15 37752233
2010 Epithelial Protein Lost in Neoplasm alpha (Eplin-alpha) is transcriptionally regulated by G-actin and MAL/MRTF coactivators. Molecular cancer 13 20236507
2022 EPLIN, a Putative Tumour Suppressor in Colorectal Cancer, Implications in Drug Resistance. International journal of molecular sciences 8 36499558
2024 M6A modification-mediated LIMA1 promotes the progression of hepatocellular carcinoma through the wnt-βcatenin/Hippo pathway. Cell biology and toxicology 7 39707043
2025 LIMA1 O-GlcNAcylation Promotes Hepatic Lipid Deposition through Inducing β-catenin-Regulated FASn Expression in Metabolic Dysfunction-Associated Steatotic Liver Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 6 39921472
2023 EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration. Journal of cell science 6 37325974
2018 FRET-based tension measurement across actin-associated mechanotransductive structures using Lima1. The International journal of developmental biology 6 30378387
2007 Characterization of porcine EPLIN gene revealed distinct expression patterns for the two isoforms. Animal biotechnology 6 17453649
2024 Nuclear-cytoplasmic translocation of SQSTM1/p62 protein enhances ESCC cell migration and invasion by stabilizing EPLIN expression. Experimental cell research 5 38185251
2025 An antagonistic role of clock genes and lima1 in kidney regeneration. Communications biology 3 39789202
2024 The concerted action of SEPT9 and EPLIN modulates the adhesion and migration of human fibroblasts. Life science alliance 3 38719752
2021 Epithelial protein lost in neoplasm (EPLIN) and prostate cancer: lessons learned from the ARCaP model. American journal of clinical and experimental urology 3 34541025
2025 A specific role for endothelial EPLIN-isoform-regulated actin dynamics in neutrophil transmigration. Scientific reports 2 40325158
2024 LIMA1 links the E3 ubiquitin ligase RNF40 to lipid metabolism. Cell death discovery 2 38909032
2025 Identification of a small molecule targeting EPLIN as a novel strategy for the treatment of pediatric neuroblastoma and medulloblastoma. Cell death & disease 1 40701975
2024 Expression and molecular insights of lima1 in cholangiocarcinoma. Cell adhesion & migration 1 39076043
2026 Bisphosphate nucleotidase 1 promotes progression and docetaxel resistance in triple-negative breast cancer via STUB1-mediated destabilization of LIMA1. Cell death & disease 0 41540000
2026 Inhibition of Breast Cancer Bone Metastasis by LRP5-Overexpressing Osteocytes via the LIMA1/MYO5B Signaling Axis. International journal of molecular sciences 0 41596426
2025 LIMA1 inhibits cisplatin resistance and malignant biological behavior of bladder cancer cells by suppressing the Wnt/β-catenin pathway. BMC medical genomics 0 40269880
2025 IRBIT and LIMA1 associate with and are necessary for epithelial cell SLC26A3 (DRA) stimulation by cAMP/ATP. American journal of physiology. Cell physiology 0 40569378
2025 LIMA1-alpha staining predicts curative intent surgery response in HPV negative head and neck cancer. EMBO molecular medicine 0 40676267
2025 Checking in with EPLIN: EPLINα as a regulator of integrin trafficking. Developmental cell 0 41253111
2025 Albacarcin V adds EPLIN as a novel and promising target for the treatment of female cancers and pediatric medulloblastoma. Biochemical pharmacology 0 41360228
2024 EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer. Scientific reports 0 39730634