Affinage

LIMA1

LIM domain and actin-binding protein 1 · UniProt Q9UHB6

Length
759 aa
Mass
85.2 kDa
Annotated
2026-06-10
59 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIMA1 (EPLIN) is an actin-binding and cross-linking protein that governs the stability and architecture of the actin cytoskeleton, acting broadly as a suppressor of cell motility, invasion, and proliferation (PMID:10618726, PMID:12566430). Biochemically, purified LIMA1 uses at least two actin-binding sites to inhibit filament depolymerization, bundle filaments, and block Arp2/3-mediated branching nucleation, thereby favoring stable structures such as stress fibers over dynamic membrane ruffles (PMID:12566430). Through direct binding to α-catenin it links the cadherin–catenin and VE-cadherin–catenin complexes to F-actin, forming the molecular bridge required to build and maintain the epithelial and endothelial adhesion belt (zonula adherens) and to recruit vinculin under junctional tension (PMID:18093941, PMID:22194609, PMID:21844208). Its two isoforms are functionally and transcriptionally distinct: EPLIN-alpha is serum/RhoA- and MAL/MRTF-SRF-inducible and terminates membrane protrusion growth via Arp2/3, whereas the more stable EPLIN-beta stabilizes stress fibers (PMID:10806352, PMID:20236507, PMID:31644899). LIMA1 abundance and actin affinity are tightly controlled by post-translational modification, including ERK phosphorylation that lowers actin affinity and triggers ubiquitin-proteasomal turnover to permit stress-fiber disassembly and migration (PMID:17875928, PMID:23188829), CDK1 phosphorylation at Ser203 that remodels the mitotic actin cortex for correct spindle positioning (PMID:42237003), O-GlcNAcylation at T662 that stabilizes the protein and drives hepatocyte lipid deposition (PMID:39921472), and degradation by multiple E3 ligases including the Rab40b-Cullin5 complex, RNF40, and STUB1 (PMID:33999101, PMID:38909032, PMID:41540000). Beyond junctions, LIMA1 functions in cytokinesis by promoting accumulation of active myosin II and Sept2 at the cleavage furrow (PMID:19221476), restricts primary ciliogenesis together with LUZP1 by stabilizing actin (PMID:32496561), and bridges NPC1L1 to a myosin Vb transport complex to drive intestinal cholesterol absorption, with Lima1-deficient mice resistant to diet-induced hypercholesterolemia (PMID:29880681). As a tumor suppressor it is transcriptionally induced by p53 and repressed by DNp73, and can be proteolytically inactivated by the API2-MALT1 paracaspase to generate an oncogenic LIM-domain fragment (PMID:25569716, PMID:28093207, PMID:24135282).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 1999 Medium

    Established LIMA1/EPLIN as a cytoskeleton-associated LIM domain protein whose overexpression restrains proliferation, framing it as a candidate growth suppressor tied to actin.

    Evidence Overexpression and immunofluorescence co-localization with F-actin in cultured cells

    PMID:10618726

    Open questions at the time
    • No biochemical mechanism for actin interaction
    • Did not distinguish isoform-specific roles functionally
  2. 2000 Medium

    Showed the two isoforms arise from distinct promoters under different transcriptional control, explaining how EPLIN-alpha is coupled to Rho/serum signaling while EPLIN-beta is constitutive.

    Evidence 5' RACE, S1 protection, promoter-reporter assays with serum and RhoA

    PMID:10806352

    Open questions at the time
    • Did not define functional consequences of differential expression
    • Transcription factor identity at the SRE not resolved here
  3. 2002 Medium

    Mapped the growth-suppressive function to the N-terminal actin-localizing region, establishing that cytoskeletal targeting, not the LIM domain, drives suppression of anchorage-independent growth.

    Evidence Truncation mutant retroviral transduction with colony formation assays

    PMID:11950948

    Open questions at the time
    • Biochemical activity of the N-terminus on actin not yet defined
    • LIM domain function left unexplained
  4. 2003 High

    Defined the core biochemical activity: LIMA1 cross-links and stabilizes actin filaments and inhibits Arp2/3 branching, providing the mechanistic basis for its bias toward stable cytoskeletal structures.

    Evidence In vitro reconstitution with purified protein (depolymerization, bundling, Arp2/3 branching) plus cellular gain/loss of function

    PMID:12566430

    Open questions at the time
    • Did not identify in vivo binding partners beyond actin
    • Regulation of the two actin-binding sites unresolved
  5. 2007 High

    Identified LIMA1 as the α-catenin–F-actin bridge that builds the adhesion belt, answering how the cadherin-catenin complex couples to a stable actin ring.

    Evidence RNAi, reciprocal Co-IP, and live imaging in epithelial cells

    PMID:18093941

    Open questions at the time
    • Mechanical regulation of the bridge not addressed
    • Did not test endothelial/VE-cadherin junctions
  6. 2007 High

    Placed LIMA1 under ERK control, showing phosphorylation lowers actin affinity to permit stress-fiber disassembly and migration, providing a switch between stable and dynamic cytoskeletal states.

    Evidence In vitro kinase assay, phospho-site mutagenesis, PDGF-stimulated migration assays

    PMID:17875928

    Open questions at the time
    • Link between phosphorylation and protein turnover not yet made
    • Did not address junctional pools of LIMA1
  7. 2008 Medium

    Connected LIMA1 to cancer cell behavior, demonstrating it suppresses invasion/motility downstream of ERK signaling.

    Evidence Overexpression with invasion/migration assays and ERK inhibition in breast cancer cells

    PMID:18796137

    Open questions at the time
    • Molecular target of ERK-LIMA1 axis in invasion not dissected
    • In vivo relevance not tested
  8. 2010 Medium

    Showed actin-MAL/MRTF-SRF signaling drives EPLIN-alpha transcription, establishing a feedback link between actin dynamics and isoform expression.

    Evidence Transcriptomics with actin drugs, promoter-reporter, ChIP, dominant-negative MAL

    PMID:20236507

    Open questions at the time
    • Physiological trigger of this feedback in vivo unclear
    • EPLIN-beta regulatory inputs not identified
  9. 2009 Medium

    Extended LIMA1 function to cytokinesis, showing it concentrates contractile machinery (myosin II, Sept2, RhoA/Cdc42) at the cleavage furrow to prevent multinucleation.

    Evidence siRNA knockdown, co-localization, and multinucleation scoring

    PMID:19221476

    Open questions at the time
    • Direct versus indirect interaction with furrow components not resolved
    • No biochemical binding data for myosin II/Sept2
  10. 2011 High

    Resolved the mechanics and partners of junctional LIMA1 across endothelium and epithelium, showing it tethers VE-cadherin/catenin to actin and that junctional tension retains it to recruit vinculin and maintain zonula adherens morphology.

    Evidence Co-IP/GST pulldown, tension manipulation, αE-catenin–EPLIN fusion, angiogenesis assays

    PMID:21625216 PMID:21844208 PMID:22194609

    Open questions at the time
    • Force-sensing mechanism that ejects LIMA1 under tension not molecularly defined
    • Relationship between AJ and EMT roles incompletely integrated
  11. 2012 High

    Unified phosphorylation with degradation, showing EGF/ERK-dependent phosphorylation of LIMA1 triggers its ubiquitination and proteasomal turnover, explaining acute downregulation during motility induction.

    Evidence EGF stimulation, ERK inhibition, ubiquitination assay, phospho-site mutagenesis, cycloheximide chase

    PMID:23188829

    Open questions at the time
    • E3 ligase responsible not identified here
    • Spatial control of degradation unaddressed
  12. 2017 Medium

    Established transcriptional tumor-suppressor circuitry, with p53 directly inducing LIMA1 to suppress invasion and DNp73 repressing it to activate pro-metastatic IGF1R-AKT/STAT3 signaling.

    Evidence ChIP-seq, nutlin-3a activation, knockdown epistasis, xenografts (with #24135282)

    PMID:24135282 PMID:28093207

    Open questions at the time
    • Mechanism linking LIMA1 loss to IGF1R activation not biochemically defined
    • Contribution of cytoskeletal versus signaling roles to suppression unresolved
  13. 2015 Medium

    Demonstrated a non-cell-autonomous role in epithelial defense, with LIMA1 driving apical extrusion of RasV12-transformed cells upstream of Cav-1 and myosin-II/PKA.

    Evidence siRNA, co-culture extrusion assays, epistasis

    PMID:25609711

    Open questions at the time
    • Direct molecular interactions in extrusion not fully mapped
    • Generality across oncogenes unclear
  14. 2015 High

    Linked LIMA1 to integrin adhesion, showing PINCH-1-dependent recruitment to adhesion sites is required for keratinocyte spreading and migration.

    Evidence PINCH-1 interactome MS, Co-IP, conditional knockout mouse, adhesion/migration assays

    PMID:25609703

    Open questions at the time
    • Whether LIMA1 directly binds PINCH-1 not established
    • Relationship to junctional pool unclear
  15. 2015 High

    Revealed LIMA1 as a substrate of the API2-MALT1 paracaspase, showing oncogenic cleavage generates a LIM-domain-only fragment, a mechanism of tumor-suppressor inactivation in MALT lymphoma.

    Evidence Co-IP, in vitro cleavage with active-site mutagenesis, xenografts, primary tumor analysis

    PMID:25569716

    Open questions at the time
    • Function of the liberated LIM fragment not fully characterized
    • Cleavage relevance outside MALT lymphoma untested
  16. 2018 High

    Uncovered a metabolic function, showing LIMA1 bridges NPC1L1 to a myosin Vb transport complex to drive intestinal cholesterol absorption, with knockout mice and a human variant validating the pathway.

    Evidence Co-IP, knockout mouse phenotyping, human frameshift variant, brush-border localization

    PMID:29880681

    Open questions at the time
    • Structural basis of NPC1L1–LIMA1–myosin Vb assembly unknown
    • Tissue-specific regulation of this complex unresolved
  17. 2019 High

    Defined isoform-specific cytoskeletal mechanisms, showing EPLIN-alpha targets and terminates protrusions via Arp2/3 while the slower-turnover EPLIN-beta stabilizes stress fibers under shear stress.

    Evidence FRAP, isoform-specific knockdown, Arp2/3 interaction assays, shear stress in endothelial cells

    PMID:31644899

    Open questions at the time
    • Structural determinants of isoform divergence not mapped
    • In vivo isoform-specific phenotypes not tested
  18. 2020 Medium

    Identified a ciliogenesis-restricting function, with LIMA1 and LUZP1 stabilizing actin at the centrosome to limit primary cilia formation.

    Evidence BioID, Co-IP, siRNA, cilia quantification

    PMID:32496561

    Open questions at the time
    • Direct LIMA1–LUZP1 binding interface undefined
    • Mechanism of MyosinVa regulation at centrosome unclear
  19. 2021 High

    Showed spatially restricted degradation as a migration control mechanism, with the Rab40b-Cullin5 complex ubiquitylating LIMA1 at the leading edge to regulate focal adhesion and cytoskeletal dynamics.

    Evidence Co-IP, ubiquitylation assay, siRNA, focal adhesion and invasion assays

    PMID:33999101

    Open questions at the time
    • Recognition determinants on LIMA1 for Rab40b not mapped
    • Integration with ERK-driven turnover unresolved
  20. 2022 Medium

    Connected LIMA1 to pluripotency and cell mechanics, showing the naive circuit requires Lima1 to suppress blebbing and support mitochondrial energetics, enabling embryo integration.

    Evidence Knockout ESCs, live imaging, mitochondrial assays, chimera/embryo injection

    PMID:35105859

    Open questions at the time
    • Mechanistic link to mitochondrial function unexplained
    • Whether actin-bundling activity underlies the phenotype untested
  21. 2022 Medium

    Added a signaling-suppressor function, showing LIMA1 binds BMI1 to destabilize it and inhibit Wnt/β-catenin signaling in HCC.

    Evidence Co-IP, western blot, in vitro/in vivo functional assays

    PMID:36497115

    Open questions at the time
    • Direct versus adaptor-mediated BMI1 destabilization unclear
    • Reconciliation with cytoskeletal role not addressed
  22. 2023 Medium

    Expanded post-translational regulation, identifying ubiquitin-independent degradation of EPLIN-beta by antizyme Az1/OAZ1 that constrains migration.

    Evidence Quantitative proteomics, Co-IP, ubiquitination assay, Az1 knockout migration assays

    PMID:37325974

    Open questions at the time
    • Indirect interaction adaptor not identified
    • Isoform-selectivity mechanism undefined
  23. 2023 Medium

    Revealed a deubiquitination axis, showing USP44 stabilizes LIMA1 and MAD2 sequesters USP44 to promote K48-ubiquitination and degradation, activating IGF1R/PI3K/AKT.

    Evidence Co-IP, K48-linkage ubiquitination assay, fractionation, signaling analysis

    PMID:37752233

    Open questions at the time
    • E3 ligase opposing USP44 not identified
    • Physiological context of MAD2-USP44 competition unclear
  24. 2024 High

    Consolidated a multi-ligase degradation network and a metabolic-PTM axis, identifying RNF40 and STUB1 as LIMA1 E3 ligases and O-GlcNAcylation at T662 as a stabilizing modification driving hepatic lipid deposition.

    Evidence Co-IP, ubiquitination assays, domain mapping, site-specific O-GlcNAc mutagenesis with AAV rescue in knockout mice

    PMID:38909032 PMID:39921472 PMID:41540000

    Open questions at the time
    • Hierarchy/competition among the multiple E3 ligases unresolved
    • How O-GlcNAc and ubiquitin sites interplay structurally unknown
  25. 2024 Medium

    Added stabilizing partners and new actin/transport functions, including p62/SQSTM1 stabilization promoting invasion, SEPT9 binding the LIM domain to organize adhesions, EPLINα-Rab21 endosomal control of integrin recycling, and LIMA1-driven microvillus/filopodia elongation.

    Evidence GST pulldown, Co-IP, LIM-domain mapping, SEPT9 knockout rescue, BioID, integrin recycling and microscopy assays

    PMID:38185251 PMID:38719752 PMID:42202079 PMID:bio_10.1101_2024.06.27.600789

    Open questions at the time
    • Direct structural interactions for several partners undefined
    • Endosomal recycling role from preprint awaits peer review
  26. 2025 Medium

    Identified a transporter-regulatory role, showing LIMA1 forms a plasma-membrane DRA-IRBIT-LIMA1 complex required for acute cAMP/ATP stimulation of SLC26A3 anion exchange.

    Evidence Co-IP, siRNA, BCECF transport assays, surface biotinylation

    PMID:40569378

    Open questions at the time
    • Direct binding interfaces within the complex not mapped
    • In vivo relevance to intestinal physiology untested
  27. 2026 High

    Defined a mitotic regulatory mechanism, showing CDK1 phosphorylation at Ser203 reorganizes branched actin into astral structures to maintain cortical architecture and correct spindle positioning.

    Evidence In vitro CDK1 kinase assay, Ser203 mutagenesis, phospho-antibodies, live imaging, in vitro actin reconstitution

    PMID:42237003

    Open questions at the time
    • How pSer203 alters the two actin-binding sites structurally unresolved
    • Integration with cytokinesis role not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LIMA1's distinct functional pools — adherens junctions, focal/integrin adhesions, recycling endosomes, brush-border transport complexes, and the mitotic cortex — are coordinately partitioned and switched by its dense network of post-translational modifications remains unresolved.
  • No unified structural model of how PTMs gate actin-binding-site usage
  • Competition/hierarchy among multiple E3 ligases and deubiquitinases unmapped
  • Mechanistic basis for isoform-specific localization to distinct compartments incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 3 GO:0005768 endosome 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2 R-HSA-1640170 Cell Cycle 2
Partners
ACTBCTNNA1LIMS1NPC1L1RAB40BRNF40SEPT9USP44
Complex memberships
DRA-IRBIT-LIMA1 plasma membrane complexNPC1L1-myosin Vb cholesterol transport complexRab40b-Cullin5 ubiquitin ligase complexcadherin-catenin adherens junction complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 EPLIN (LIMA1) is a novel cytoskeletal LIM domain protein that co-localizes with filamentous actin and suppresses cell proliferation when overexpressed; both EPLIN-alpha and EPLIN-beta isoforms localize to actin stress fibers. Overexpression, immunofluorescence co-localization with F-actin Oncogene Medium 10618726
2000 EPLIN-alpha and EPLIN-beta are generated from distinct promoters of a single gene; EPLIN-alpha expression is serum-inducible via a consensus serum response element, and its promoter activity is enhanced by activated RhoA, whereas EPLIN-beta is not serum-regulated. 5' RACE, S1 nuclease protection, promoter-reporter constructs, serum stimulation, RhoA transfection Gene Medium 10806352
2002 The N-terminal region of EPLIN is necessary for both localization to the actin cytoskeleton and suppression of anchorage-independent growth of EWS/Fli-1- and Cdc42-transformed cells; the LIM domain and C-terminal region are dispensable for these functions. Inhibition of anchorage-independent growth requires EPLIN's actin cytoskeletal localization. Retroviral transduction of truncation mutants, colony formation assay, immunofluorescence Molecular biology of the cell Medium 11950948
2003 Purified recombinant EPLIN inhibits actin filament depolymerization, cross-links filaments into bundles via at least two actin-binding sites, and inhibits Arp2/3-mediated branching nucleation without affecting spontaneous polymerization kinetics or barbed-end elongation. EPLIN promotes stable actin filament structures (stress fibers) at the expense of dynamic structures (membrane ruffles). In vitro actin polymerization/depolymerization assays, actin bundling assay, Arp2/3 branching assay with purified recombinant EPLIN, cell overexpression/knockdown The Journal of cell biology High 12566430
2007 EPLIN couples with alpha-catenin and links the cadherin-catenin complex to F-actin, forming the molecular bridge required for the adhesion belt (zonula adherens). EPLIN depletion disorganizes the adhesion belt and converts it to zipper-like junctions with radially arranged actin fibers without affecting non-junctional actin fibers. RNAi knockdown, co-immunoprecipitation, immunofluorescence, live imaging of epithelial cells Proceedings of the National Academy of Sciences of the United States of America High 18093941
2007 ERK phosphorylates EPLIN at Ser360, Ser602, and Ser692 in vitro and in intact cells; phosphorylation of the C-terminal region reduces EPLIN's affinity for actin filaments. ERK-mediated phosphorylation of EPLIN is required for PDGF-induced stress fiber disassembly, membrane ruffling, and cell migration; a non-phosphorylatable EPLIN mutant blocks these processes. In vitro kinase assay, phospho-specific antibodies, site-directed mutagenesis (Ser→Ala), wound healing and migration assays, PDGF stimulation Molecular and cellular biology High 17875928
2008 Overexpression of EPLIN-alpha in breast cancer cells renders them less invasive and less motile; an ERK inhibitor abolishes the effects of EPLIN expression on cell behavior, placing EPLIN downstream of ERK signaling in motility control. Transfection/overexpression, in vitro invasion assay, Electric Cell Impedance Sensing migration assay, ERK inhibitor treatment Molecular cancer Medium 18796137
2009 EPLIN localizes to the cleavage furrow during cytokinesis, possibly via association with contractile ring components myosin II and septin Sept2. EPLIN depletion leads to multinucleated cells due to inefficient accumulation of active myosin II (MRLC-S19), Sept2, RhoA, and Cdc42 at the cleavage furrow. Immunofluorescence, siRNA knockdown, co-localization with myosin II and Sept2, multinucleation assay Cell cycle Medium 19221476
2010 EPLIN-alpha transcription is regulated by actin-MAL/MRTF-SRF signaling; MAL/MRTF coactivator binds an SRF consensus site in the EPLIN-alpha promoter, and its recruitment is enhanced upon induction. Monomeric actin maintains a repressive MAL-actin complex. EPLIN-beta isoform is not regulated by this pathway. Transcriptome analysis with actin-binding drugs, promoter-reporter assay, ChIP, dominant negative MAL overexpression, MRTF knockdown Molecular cancer Medium 20236507
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. EPLIN-depleted endothelial cells have reduced capacity to form pseudocapillary networks due to breakage events, establishing EPLIN as a mechanotransmitter for vinculin recruitment to adherens junctions independent of actomyosin tension. Co-immunoprecipitation, GST pulldown, siRNA knockdown, Matrigel angiogenesis assay, blebbistatin treatment, immunofluorescence The Journal of biological chemistry High 22194609
2011 EPLIN depletion in prostate cancer cells causes disassembly of adherens junctions, actin remodeling, and activation of beta-catenin signaling, demonstrating EPLIN as a negative regulator of EMT. siRNA knockdown, biochemical analysis, beta-catenin reporter assay, microarray expression analysis Oncogene Medium 21625216
2011 Junctional tension is important for retaining EPLIN at adherens junctions; lateral actin fiber force inhibits EPLIN-AJ association. EPLIN association with αE-catenin is required for zonula adherens maintenance; vinculin cooperates with EPLIN to maintain ZA morphology. A fusion of αE-catenin and EPLIN promotes ZA but not punctate AJ formation. Live imaging, tension manipulation, EPLIN-catenin fusion protein expression, RNAi, immunofluorescence The Journal of cell biology High 21844208
2012 EGF promotes phosphorylation, ubiquitination, and proteasomal degradation of EPLIN through ERK1/2-dependent signaling. Serine residues S362 and S604 are ERK1/2 phosphorylation sites; point mutation of these renders EPLIN resistant to EGF-induced protein turnover. EGF stimulation, ERK1/2 inhibitor treatment, ubiquitination assay, site-directed mutagenesis (S362A, S604A), cycloheximide chase, western blot The Journal of biological chemistry High 23188829
2013 DNp73 drives cancer cell migration/invasion by repressing EPLIN (LIMA1) expression. EPLIN directly links to IGF1R-AKT/STAT3 activation; EPLIN loss activates this signaling axis. p73/DNp73 transcriptionally regulates LIMA1/EPLIN, and the DNp73-EPLIN axis controls IGF1R-dependent signaling to initiate metastasis. Knockdown of endogenous DNp73, tumor xenografts, biochemical signaling analysis (AKT/STAT3 phosphorylation), epistasis experiments Cancer cell Medium 24135282
2015 API2-MALT1 fusion protein induces paracaspase-mediated proteolytic cleavage of LIMA1/EPLIN tumor suppressor. API2-dependent binding targets LIMA1 for MALT1 paracaspase cleavage, generating an oncogenic LIM domain-only (LMO) fragment. Primary MALT lymphomas with API2-MALT1 fusion uniquely show LIMA1 cleavage fragments. Co-immunoprecipitation, in vitro cleavage assay, mutagenesis of paracaspase active site, tumor xenograft, primary lymphoma tissue analysis Nature communications High 25569716
2015 EPLIN (LIMA1) accumulates in RasV12-transformed cells surrounded by normal cells and is required for their apical extrusion. EPLIN functions upstream of Cav-1 and promotes its enrichment in transformed cells. EPLIN regulates non-cell-autonomous activation of myosin-II and PKA in transformed cells, and affects accumulation of filamin A in neighboring normal cells. siRNA knockdown, immunofluorescence, co-culture assay, epithelial extrusion quantification Journal of cell science Medium 25609711
2015 PINCH-1 (LIMS1) associates with EPLIN at integrin adhesion sites. EPLIN localizes to integrin adhesion sites in a PINCH-1-dependent manner. EPLIN depletion severely attenuates keratinocyte spreading and migration on collagen and fibronectin without affecting PINCH-1 levels in focal adhesions. PINCH-1 interactome isolation (MS), co-immunoprecipitation, PINCH-1 conditional knockout mouse model, siRNA knockdown, adhesion and migration assays Journal of cell science High 25609703
2017 p53 transcriptionally induces LIMA1/EPLIN expression via two p53 response elements identified by ChIP-seq in the LIMA1 gene. p53-induced LIMA1 suppresses cancer cell invasion; LIMA1 knockdown partially inhibits p53-induced suppression of invasion. ChIP-seq, cDNA microarray, nutlin-3a treatment (p53 activation), siRNA knockdown, invasion assay Cancer letters Medium 28093207
2018 LIMA1 (EPLIN) bridges NPC1L1, the essential cholesterol absorption protein, to a transport complex containing myosin Vb, facilitating intestinal cholesterol uptake. In mice, LIMA1 is expressed in the small intestine and localizes on the brush border membrane. Lima1-deficient mice display reduced cholesterol absorption and resistance to diet-induced hypercholesterolemia. Co-immunoprecipitation, genetic knockout mouse model, rare human frameshift variant analysis, subcellular fractionation/localization Science High 29880681
2018 Paxillin binds to EPLIN specifically in mixed cultures of normal and RasV12-transformed cells. Paxillin, plectin, and EPLIN mutually influence each other's non-cell-autonomous accumulation. Paxillin acts downstream of plectin-EPLIN complex and promotes microtubule acetylation by suppressing HDAC6 activity to drive apical extrusion of transformed cells. Co-immunoprecipitation, immunofluorescence, siRNA knockdown, HDAC6 activity assay, tubulin acetylation measurement Scientific reports Medium 29391412
2019 EPLIN-alpha and EPLIN-beta isoforms have distinct spatiotemporal interactions with actin: EPLIN-alpha is targeted to membrane protrusions and terminates their growth via interaction with Arp2/3 complex, while EPLIN-beta stabilizes stress fibers. FRAP analyses demonstrate EPLIN-beta has a lower turnover rate than EPLIN-alpha. Shear stress increases EPLIN-beta expression to stabilize stress fibers. FRAP, siRNA isoform-specific knockdown, Arp2/3 interaction assay, immunofluorescence, shear stress experiments in endothelial cells Cell reports High 31644899
2020 LUZP1 and EPLIN interact and together restrict primary cilia formation by stabilizing actin filaments. EPLIN depletion increases MyosinVa levels at the centrosome and promotes ciliogenesis. Both proteins mobilize ARP2 to centrosomes and interact with ciliogenesis/cilia-length regulators. LUZP1 and EPLIN represent novel players in actin-dependent centrosome to basal body conversion. Proximity-ligation (BioID), siRNA knockdown, co-immunoprecipitation, cilia formation quantification, immunofluorescence The Journal of cell biology Medium 32496561
2021 Rab40b-Cullin5 complex ubiquitylates and degrades EPLIN. Rab40b directly binds EPLIN. Rab40b-Cullin5-dependent localized ubiquitylation and degradation of EPLIN at the leading edge regulates focal adhesion and cytoskeletal dynamics, promoting cell migration and invasion. Co-immunoprecipitation, ubiquitylation assay, siRNA knockdown, focal adhesion dynamics assay, invasion assay 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 for suppression of membrane blebbing and proper mitochondrial energetics. Forced Lima1 expression enables primed pluripotent stem cells to integrate into pre-implantation embryos. Lima1 knockout ESC lines, live imaging, mitochondrial function assays, chimera assay, embryo injection Nature communications Medium 35105859
2022 LIMA1 inhibits the Wnt/β-catenin signaling pathway in HCC cells by binding to BMI1 and inducing its destabilization. LIMA1 overexpression suppresses HCC cell proliferation and metastasis in vitro and in vivo. Co-immunoprecipitation, western blot, in vitro and in vivo functional assays, siRNA knockdown Cells Medium 36497115
2023 EPLIN-beta (but not EPLIN-alpha) is a substrate of ornithine decarboxylase antizyme 1 (Az1/OAZ1). The interaction between EPLIN-beta and Az1 is indirect, and EPLIN-beta is degraded by Az1 in a ubiquitination-independent manner. Az1 absence leads to elevated EPLIN-beta levels and enhanced cellular migration. Quantitative proteomics, co-immunoprecipitation, ubiquitination assay, Az1 knockout, migration assay Journal of cell science Medium 37325974
2023 MAD2 interferes with binding of the deubiquitinase USP44 to LIMA1 by sequestering USP44 in the nucleus, leading to impaired USP44/LIMA1 complex formation and enhanced K48-linked ubiquitination of LIMA1, promoting its degradation and activating the IGF1R/PI3K/AKT pathway. Co-immunoprecipitation, ubiquitination assay (K48-linkage specific), subcellular fractionation, siRNA knockdown, PI3K/AKT signaling analysis Oncogene Medium 37752233
2024 RNF40, an E3 ubiquitin ligase, directly mediates ubiquitination of LIMA1 and promotes its proteasome-dependent degradation in the cytoplasm. The 1-166 aa fragment of LIMA1 is required for interaction with RNF40. RNF40-mediated LIMA1 degradation suppresses lipid accumulation. Co-immunoprecipitation, ubiquitination assay, domain truncation mapping, proteasome inhibitor treatment, lipid accumulation assay Cell death discovery Medium 38909032
2024 LIMA1 O-GlcNAcylation at T662, catalyzed by OGT (facilitated by HCF1 upregulation under steatosis), inhibits ubiquitin-dependent degradation of LIMA1 and enhances hepatocyte lipid deposition by activating β-catenin/FASn signaling. AAV-mediated T662 mutant LIMA1 (non-O-GlcNAcylatable) decreases steatosis, insulin resistance, inflammation and fibrosis in LIMA1 hepatocyte-specific knockout mice. O-GlcNAcylation mapping (site-specific), site-directed mutagenesis (T662A), AAV rescue in HKO mice, ubiquitination assay, western blot, metabolic phenotyping Advanced science High 39921472
2024 Cytoplasmic p62 (SQSTM1) interacts with EPLIN via GST pulldown and stabilizes EPLIN protein, enhancing EPLIN-dependent migration and invasion of esophageal squamous cell carcinoma cells. GST pulldown, co-immunoprecipitation, siRNA knockdown, protein stability assay, migration/invasion assays Experimental cell research Medium 38185251
2024 STUB1 (E3 ubiquitin ligase) is recruited by BPNT1 to induce proteasomal degradation of LIMA1, promoting EMT and TNBC progression. Re-expression of LIMA1 in BPNT1-overexpressing cells partially attenuates BPNT1-driven EMT. Co-immunoprecipitation, ubiquitination/proteasomal degradation assay, re-expression rescue experiment, in vitro and in vivo functional assays Cell death & disease Medium 41540000
2024 SEPT9 directly interacts with the single LIM domain of EPLIN. SEPT9 depletion decreases cell adhesion and migration; these defects can be partly rescued by increased EPLIN levels. SEPT9 and EPLIN together regulate actin-related filopodia, stress fiber organization, and focal adhesion size. SEPT9 knockout fibroblasts, co-immunoprecipitation, LIM-domain interaction mapping, rescue by EPLIN overexpression, focal adhesion analysis, actin imaging Life science alliance Medium 38719752
2025 LIMA1 associates with IRBIT and the intestinal Cl-/HCO3- exchanger SLC26A3 (DRA). cAMP/ATP stimulation increases co-precipitation of LIMA1 with both IRBIT and DRA. Knockdown of LIMA1 reduces cAMP plus ATP stimulation of DRA but does not alter basal DRA activity, establishing a DRA-IRBIT-LIMA1 plasma membrane complex required for acute stimulation of DRA. Co-immunoprecipitation, siRNA knockdown, functional DRA transport assay (BCECF fluorometry), surface biotinylation American journal of physiology. Cell physiology Medium 40569378
2026 CDK1 phosphorylates EPLIN at Ser203 during mitosis. This phosphorylation is required for EPLIN to maintain proper actin cortex architecture and correct spindle positioning. EPLIN-pSer203 enhances the ability of EPLIN to reorganize branched actin filaments into astral structures in vitro, sequestering actin bundles and Arp2/3 complex to prevent excessive de novo actin polymerization. EPLIN depletion causes spindle deviation and metaphase arrest with abnormal cortical actin accumulation and blebbing. In vitro kinase assay (CDK1), site-directed mutagenesis (Ser203), phospho-specific antibodies, siRNA depletion, live-cell imaging, in vitro actin reconstitution assay Communications biology High 42237003
2026 LIMA1 expression is sufficient to drive elongation of microvilli in epithelial cells and formation and stabilization of exaggerated filopodia in non-epithelial cells. Individual filopodia in LIMA1-overexpressing cells exhibit merging dynamics that enable formation of large core actin bundles from smaller precursors. In tuft cells, LIMA1 is restricted to the basal/rootlet ends of actin bundles. Live-cell and electron microscopy, LIMA1 overexpression, filopodia dynamics analysis, LIMA1-specific localization in tuft cells Molecular biology of the cell Medium 42202079
2024 EPLINα localizes to Rab21-positive recycling endosomes in an actin-binding-dependent manner and interacts with Rab21. EPLINα supports beta1-integrin recycling and cell migration. Coronin 1C was identified as an EPLINα proximal protein at Rab21-containing endosomes in an EPLINα-dependent manner. EPLINβ resides on actin stress fibers and does not show this endosomal localization. BioID proximity labeling, co-localization (confocal), co-immunoprecipitation, integrin recycling assay, migration assay, isoform-specific expression constructs bioRxivpreprint Medium bio_10.1101_2024.06.27.600789

Source papers

Stage 0 corpus · 59 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 320 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.) 119 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
2011 EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis. Oncogene 71 21625216
2015 EPLIN is a crucial regulator for extrusion of RasV12-transformed cells. Journal of cell science 70 25609711
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 41 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 29 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
2024 Lipotoxic hepatocyte derived LIMA1 enriched small extracellular vesicles promote hepatic stellate cells activation via inhibiting mitophagy. Cellular & molecular biology letters 21 38822260
2021 Rab40-Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration. The Journal of cell biology 21 33999101
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 9 36499558
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) 7 39921472
2024 M6A modification-mediated LIMA1 promotes the progression of hepatocellular carcinoma through the wnt-βcatenin/Hippo pathway. Cell biology and toxicology 7 39707043
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
2024 LIMA1 links the E3 ubiquitin ligase RNF40 to lipid metabolism. Cell death discovery 4 38909032
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
2025 LIMA1 inhibits cisplatin resistance and malignant biological behavior of bladder cancer cells by suppressing the Wnt/β-catenin pathway. BMC medical genomics 1 40269880
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
2026 A role for LIMA1 in the assembly of actin bundle-supported protrusions. Molecular biology of the cell 0 42202079
2026 CDK1-mediated phosphorylation of EPLIN is crucial for mitotic spindle positioning. Communications biology 0 42237003
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

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