Affinage

EPB41L3

Band 4.1-like protein 3 · UniProt Q9Y2J2

Length
1087 aa
Mass
120.7 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EPB41L3 (protein 4.1B/DAL-1) is a FERM-domain-containing membrane-cytoskeletal adaptor that functions as a tumor suppressor and an organizer of specialized axonal membrane domains. Its FERM domain directly engages transmembrane partners—including TSLC1/CADM1, EGFR, and Caspr/Caspr2—while its C-terminal domain binds β8 integrin and its U2 domain, when membrane-localized, activates a Src–Rac1–JNK growth-suppressive cascade; it inhibits EGFR dimerization/autophosphorylation to dampen MAPK/ERK and PI3K/AKT signaling, induces caspase-8-mediated apoptosis, and maintains E-cadherin expression to oppose epithelial–mesenchymal transition (PMID:31492173, PMID:16420693, PMID:27312663, PMID:16707455). In myelinated neurons, 4.1B is essential for anchoring Caspr at paranodes and Caspr2/Kv1 channels at juxtaparanodes, thereby establishing the membrane barriers that compartmentalize ion channels around nodes of Ranvier, as demonstrated by loss of these domains in 4.1B-null mice (PMID:20164332, PMID:21632923). A 200 kDa isoform localizes to the Golgi apparatus and is required for trafficking of Na⁺/K⁺-ATPase and tight-junction proteins to the plasma membrane (PMID:19299464).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 Medium

    Establishing the basic identity of 4.1B as a plasma-membrane adaptor at cell–cell contacts with tissue-specific alternative splicing resolved what domain architecture underlies this new 4.1 family member.

    Evidence In situ hybridization, immunofluorescence, and splicing analysis in multiple tissues

    PMID:10652311

    Open questions at the time
    • No functional consequence of alternative splicing shown
    • No binding partners identified at this stage
  2. 2001 Medium

    Demonstrating that DAL-1 interacts with ERM proteins and βII-spectrin and suppresses meningioma cell growth established it as a candidate tumor suppressor linked to the cortical cytoskeleton.

    Evidence Co-immunoprecipitation and proliferation assays in meningioma and schwannoma cells

    PMID:11300722 PMID:11996670

    Open questions at the time
    • Mechanism of growth suppression unknown
    • Cell-type specificity unexplained
  3. 2002 High

    Identification of direct TSLC1/CADM1 binding and co-redistribution to membrane ruffles linked 4.1B to a known tumor suppressor pathway and implicated it in actin-dependent cell motility and metastasis suppression.

    Evidence Reciprocal co-immunoprecipitation, actin disruption, and in vivo metastasis model

    PMID:12115567 PMID:12234973

    Open questions at the time
    • Structural basis of TSLC1 interaction not yet resolved
    • Downstream signaling from the 4.1B–TSLC1 complex unknown
  4. 2003 High

    Discovery that 4.1B binds Caspr at paranodes and Caspr2 at juxtaparanodes through conserved GNP motifs established a neuronal role entirely distinct from tumor suppression.

    Evidence In vitro binding and co-immunoprecipitation from brain homogenates with immunofluorescence in developing CNS/PNS

    PMID:12542678

    Open questions at the time
    • In vivo requirement not yet tested by knockout
    • Whether 4.1B is sufficient or redundant with other 4.1 proteins at nodes unknown
  5. 2004 High

    Showing that the FERM domain inhibits PRMT3 methyltransferase activity without being a substrate itself revealed an unexpected enzymatic regulatory function and linked 4.1B to protein arginine methylation.

    Evidence Yeast two-hybrid, co-IP, GST binding, and in vitro methylation assays in MCF-7 cells

    PMID:15334060

    Open questions at the time
    • Physiological relevance of PRMT3 inhibition to tumor suppression not demonstrated
    • Whether endogenous methylation targets change in 4.1B-expressing cells unclear
  6. 2005 Medium

    Domain dissection identified the U2 domain as the minimal growth-suppressive unit when membrane-targeted, and showed 4.1B induces G1 arrest with decreased cyclin A and Rb phosphorylation in mammary epithelium, separating the mechanism from 14-3-3 binding.

    Evidence Deletion mutants with clonogenic/caspase-3 assays; 4.1B-null mouse mammary gland analysis; 14-3-3-binding-defective mutant retaining growth suppression

    PMID:15116094 PMID:15688033 PMID:15737618 PMID:16007173 PMID:16157875

    Open questions at the time
    • U2 domain binding partners mediating growth suppression not identified
    • How membrane localization activates U2-dependent signaling unknown
  7. 2006 Medium

    Epistasis experiments placing Src→Rac1→JNK downstream of membrane-localized 4.1B, and identification of caspase-8 as the apoptotic effector, defined two parallel pathways through which 4.1B suppresses growth.

    Evidence Pharmacologic/dominant-negative inhibition of Rac1/JNK in meningioma cells; caspase-8 inhibition in MCF-7 cells

    PMID:16420693 PMID:16707455

    Open questions at the time
    • How U2 domain activates Src not known
    • Whether JNK and caspase-8 pathways converge or act in different cell types unclear
  8. 2007 High

    In vivo loss-of-function in prostate cancer models proved 4.1B is a bona fide metastasis suppressor, while bidirectional manipulation in sarcoma cells showed it directly controls actin stress fibers and migration speed.

    Evidence shRNA orthotopic prostate model, 4.1B-null spontaneous tumor study, RNAi/re-expression migration assays in sarcoma cells

    PMID:17264155 PMID:17640904

    Open questions at the time
    • Whether metastasis suppression depends on TSLC1, Src–Rac1–JNK, or another pathway not resolved
    • Actin-organizing mechanism at the molecular level not defined
  9. 2009 Medium

    Discovery that a 200 kDa Golgi-localized isoform is required for trafficking of Na⁺/K⁺-ATPase and ZO-1/ZO-2 to the plasma membrane, and that 4.1B acts as an intracellular effector of SynCAM1 to recruit NMDARs, expanded the functional repertoire beyond cortical cytoskeletal scaffolding.

    Evidence siRNA depletion with Golgi and trafficking phenotypes; SynCAM1–4.1B coculture assay with electrophysiology in hippocampal neurons

    PMID:19299464 PMID:19796685

    Open questions at the time
    • Golgi isoform domain requirements not mapped
    • Whether NMDAR recruitment occurs in vivo not confirmed
  10. 2010 High

    Transgenic rescue in 4.1B-null mice proved the 4.1-binding motifs of Caspr and Caspr2 are individually required for paranodal barrier function and juxtaparanodal Kv1 channel clustering, establishing 4.1B as an essential axonal domain organizer.

    Evidence Caspr/Caspr2 transgenes lacking 4.1-binding sequence in 4.1B-null mice with Kv1 channel localization

    PMID:20164332

    Open questions at the time
    • Whether 4.1B directly connects Caspr/Caspr2 to spectrin in vivo not biochemically shown
    • Functional consequences for nerve conduction not fully characterized at this point
  11. 2011 High

    Independent 4.1B-null mouse studies confirmed paranodal AGSJ destabilization, loss of juxtaparanodal Caspr2/Kv1, reduced βII-spectrin, and extended the phenotype to the para-AIS compartment, consolidating 4.1B as the primary cytoskeletal anchor at multiple axonal domains; the crystal structure of FERM–TSLC1 defined the atomic basis of the key tumor-suppressive interaction.

    Evidence Two independent 4.1B-null lines with ultrastructural EM and electrophysiology; X-ray crystallography with SPR and mutagenesis

    PMID:21131357 PMID:21632923 PMID:21958379 PMID:21966409

    Open questions at the time
    • Why 4.1G partially compensates in CNS but not PNS remains unclear
    • Structural basis for U2 domain signaling still unknown
  12. 2012 High

    Showing that 4.1B is expressed by neurons in all myelinated domains except nodes, and that juxtaparanodal defects are neuron-autonomous, resolved the cell-of-origin question and revealed additional roles in controlling myelin thickness and Schmidt-Lanterman incisures.

    Evidence 4.1B-null mice, immuno-EM, myelinating neuron-Schwann cell cocultures

    PMID:23109359

    Open questions at the time
    • How 4.1B loss leads to hypermyelination is mechanistically unexplained
    • Whether internodal Necl loss is cause or consequence of myelin defects unclear
  13. 2016 Medium

    Demonstrating that 4.1B loss in SV40T-immortalized MEFs is sufficient for malignant transformation with E-cadherin loss, nuclear β-catenin, and ERK/AKT activation—and that 4.1B physically interacts with E-cadherin—unified tumor suppression with adherens junction maintenance.

    Evidence 4.1B-null iMEF xenograft, co-immunoprecipitation of 4.1B–E-cadherin, pathway western blots

    PMID:27312663

    Open questions at the time
    • Whether 4.1B stabilizes E-cadherin at the membrane or regulates its transcription not separated
    • Relative contributions of EGFR, E-cadherin, and Src–Rac1 pathways to transformation not ranked
  14. 2019 Medium

    Mapping the FERM domain interaction to the first 13 residues of the EGFR juxtamembrane segment and showing this inhibits receptor dimerization and autophosphorylation provided a direct mechanism for 4.1B suppression of MAPK/ERK and PI3K/AKT signaling.

    Evidence Co-IP, domain-mapping constructs, EGFR dimerization/phosphorylation assays in gastric cancer lines and MEFs

    PMID:31492173

    Open questions at the time
    • Whether EGFR inhibition accounts for tumor suppression in vivo not tested
    • Structural model of FERM–EGFR complex not available

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the structural basis of U2-domain-mediated Src activation, how 4.1B loss causes hypermyelination, the relative contribution of each signaling axis (EGFR, E-cadherin/β-catenin, Src–Rac1–JNK, caspase-8) to tumor suppression in different tissues, and whether the Golgi-trafficking and synaptic NMDAR-recruitment roles are connected to the canonical membrane-cytoskeletal scaffold function.
  • No structural model for U2 domain or its effector interface
  • In vivo hierarchy among tumor-suppressive pathways not established
  • Golgi isoform biology largely unexplored beyond initial siRNA study

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0008092 cytoskeletal protein binding 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 6 GO:0005856 cytoskeleton 4 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3
Partners
CADM1CNTNAP1CNTNAP2EGFRPRMT3PRMT5SLC4A4

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 EPB41L3 (DAL-1/4.1B) directly associates with the tumor suppressor TSLC1 (CADM1) at cell-cell contact sites and links to the actin cytoskeleton; redistribution of both proteins to membrane ruffles suggests involvement in cell motility accompanying actin rearrangement. Co-immunoprecipitation, co-localization, actin disruption assays, in vivo metastasis model Cancer research High 12234973
2010 Crystal structure of the DAL-1 FERM domain in complex with the TSLC1 cytoplasmic domain revealed that DAL-1 binds TSLC1 through conserved residues in a hydrophobic pocket in the C-lobe of the FERM domain, with TSLC1 Tyr406 and Thr408 forming the most critical contacts, as confirmed by surface plasmon resonance. X-ray crystallography, surface plasmon resonance, mutagenesis The Journal of biological chemistry High 21131357
2004 The FERM domain of DAL-1/4.1B interacts with protein arginine N-methyltransferase 3 (PRMT3) via the C-terminal catalytic core domain of PRMT3; DAL-1/4.1B is not itself a PRMT3 substrate but inhibits PRMT3-mediated methylation of GAR-containing substrates both in vitro and in cells. Yeast two-hybrid, co-immunoprecipitation, in vitro GST binding, in vitro methylation assay, inducible overexpression in MCF-7 cells Oncogene High 15334060
2005 DAL-1/4.1B modulates PRMT5 activity in a substrate-specific manner: it inhibits PRMT5-mediated methylation of Sm proteins while enhancing methylation of myelin basic protein, demonstrating bidirectional regulation of PRMT5. Yeast two-hybrid, in vitro methylation assay, co-immunoprecipitation Biochemical and biophysical research communications Medium 15737618
2002 The FERM domain of DAL-1/Protein 4.1B specifically binds 14-3-3 isoforms β, γ, and η (but not other 4.1 family members such as merlin, ezrin, or radixin); the binding site was mapped to residues Pro244–Leu280 within the FERM domain. Yeast two-hybrid, GST affinity chromatography, co-immunoprecipitation The Biochemical journal Medium 11996670
2004 14-3-3 binding to Protein 4.1B (via the F359Y mutation that abolishes 14-3-3 binding without affecting other interactors) is dispensable for Protein 4.1B growth suppression in meningioma cells. Site-directed mutagenesis, GST affinity chromatography, co-immunoprecipitation, clonogenic assay, thymidine incorporation Oncogene Medium 15116094
2005 The U2 domain of Protein 4.1B, when targeted to the plasma membrane, is necessary and sufficient for meningioma growth suppression; deletion of the U2 domain abolishes growth suppression and caspase-3 activation. Truncation/deletion mutants, clonogenic assay, thymidine incorporation, caspase-3 activation assay, membrane targeting construct Oncogene Medium 15688033
2006 Protein 4.1B/DAL-1 expression in meningioma cells activates JNK through sequential activation of Src and Rac1; inhibition of Rac1 or JNK abrogates 4.1B-mediated growth suppression and cyclin A regulation; this function requires the U2 domain at the plasma membrane. Pharmacologic inhibitors, dominant-negative constructs, JNK activity assays, colony formation, cyclin A western blot Cancer research Medium 16707455
2006 DAL-1/4.1B-induced apoptosis in MCF-7 cells is primarily mediated through caspase-8 activation; inhibition of caspase-8 blocks DAL-1/4.1B-induced cell death; protein methylation cooperates with DAL-1/4.1B in this process. Flow cytometry (apoptosis), caspase activation assays, methylation inhibitor (AdOX), inducible expression system Molecular cancer Medium 16420693
2003 Protein 4.1B associates with both Caspr/paranodin (at paranodes) and Caspr2 (at juxtaparanodes) of myelinated axons through their conserved GNP motifs; these interactions were validated by co-immunoprecipitation from brain homogenates. In vitro binding assays, co-immunoprecipitation from brain homogenates, immunofluorescence in developing CNS/PNS The European journal of neuroscience High 12542678
2010 4.1B interaction with Caspr (via the 4.1-binding sequence) is required for generating an effective membrane barrier at the paranodal junction, as Caspr lacking the 4.1-binding site fails to exclude Kv1 channels from paranodes; 4.1B interaction with Caspr2 is required for Caspr2 and Kv1 channel accumulation at the juxtaparanodal membrane, demonstrated in 4.1B-null mice. Transgenic mice expressing Caspr/Caspr2 lacking 4.1-binding sequence, 4.1B-null mice, immunofluorescence, Kv1 channel localization assays The Journal of neuroscience High 20164332
2011 In 4.1B-null mice, Caspr localization is disrupted at paranodes and paranodal axoglial septate junctions (AGSJs) are destabilized in both PNS and CNS, and juxtaparanodal clustering of Caspr2/TAG-1/Kv1 channels is lost; βII spectrin enrichment along the axolemma is reduced. 4.1B-null mice (independent generation), immunofluorescence, ultrastructural EM, electrophysiology The Journal of neuroscience High 21632923 21966409
2012 4.1B is expressed by neurons subjacent to the axon membrane in all myelinated axon domains except nodes; its loss reduces internodal Necl-1, Necl-2, and α2-spectrin levels, and causes hypermyelination and increased Schmidt-Lanterman incisures; juxtaparanodal clustering defects are neuron-autonomous as shown by myelinating cocultures. 4.1B-null mice, immunofluorescence, immuno-EM, myelinating cocultures (neuron-autonomous test), nerve conduction velocity measurement Glia High 23109359
2011 Protein 4.1B is necessary to form the Caspr+ para-AIS barrier at the first myelin attachment site of motor neurons, ensuring compartmentalization of Kv1 channels and segregation of AIS, para-AIS, and juxtapara-AIS compartments. 4.1B knockout mice, immunofluorescence for AIS and nodal markers BMC biology Medium 21958379
2009 Protein 4.1B acts as an intracellular effector of SynCAM1 to recruit NMDA-type receptors (NMDARs) to SynCAM1 adhesion sites; manipulation of 4.1B expression specifically affects NMDAR-mediated activity and localization in hippocampal neurons, whereas SynCAM1-4.1N interaction specifically recruits AMPARs. COS7 cell adhesion assay, HEK293-neuron coculture assay, siRNA knockdown and overexpression in hippocampal neurons, electrophysiology (mEPSC recording) Molecular and cellular neurosciences Medium 19796685
2005 The C-terminal domain of Band 4.1B (a region conserved across 4.1 family members) interacts selectively with the β8 integrin cytoplasmic tail; 4.1B colocalizes with αvβ8 in cultured astrocytes and brain. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation, immunofluorescence colocalization Proceedings of the National Academy of Sciences of the United States of America Medium 16157875
2011 αvβ8 integrin and Band 4.1B cooperatively regulate cardiac morphogenesis: ~60% of β8/4.1B double-null mouse embryos display cardiovascular defects and die by E11.5 due to defective cardiac outflow tract development with reduced SMA-actin expression in neural crest-derived cells. Double-null mouse genetics, embryo phenotyping, immunostaining for SMA-actin Developmental dynamics Medium 21181944
2009 A 200 kDa isoform of protein 4.1B localizes to the Golgi apparatus; siRNA depletion disrupts Golgi structure and prevents Na+/K+-ATPase, ZO-1, and ZO-2 from trafficking to the plasma membrane. siRNA knockdown, Brefeldin A treatment, immunofluorescence, subcellular fractionation Journal of cell science Medium 19299464
2007 Protein 4.1B suppresses prostate cancer progression and metastasis in vivo: down-regulation of 4.1B increased metastatic propensity in an orthotopic prostate cancer model, and 4.1B-deficient mice showed increased susceptibility to spontaneous aggressive prostate carcinomas; enhanced malignancy was associated with reduced apoptosis. shRNA knockdown in orthotopic mouse model, 4.1B-null mouse spontaneous tumor study, apoptosis assays Proceedings of the National Academy of Sciences of the United States of America High 17640904
2007 RNAi-mediated knockdown of 4.1B in non-metastatic sarcoma cells reduced actin stress fibers and doubled migration speed; re-expression of 4.1B in metastatic cells halved migration speed and suppressed chemotaxis, establishing 4.1B as a regulator of actin organization and cell motility. RNAi knockdown, exogenous re-expression, wound-healing migration assay, chemotaxis assay, F-actin staining Journal of cell science Medium 17264155
2013 The 130-kDa plasma membrane isoform of protein 4.1B (but not the 60-kDa nuclear isoform) is required for cell adhesion, spreading, migration, and actin stress fiber formation in mouse embryonic fibroblasts; these defects are rescued by re-expression of the 130-kDa isoform. 4.1B KO MEFs, isoform-selective re-expression, adhesion/spreading/migration assays, F-actin staining The Journal of biological chemistry Medium 24381168
2005 4.1B inhibits mammary epithelial cell proliferation by inducing G1 cell cycle arrest with decreased cyclin A expression, reduced Rb phosphorylation, and reduced erbB2 phosphorylation, independently of MAPK, JNK, or Akt; 4.1B-null mice show increased mammary epithelial proliferation during pregnancy. 4.1B-null mice (mammary gland proliferation analysis), cell cycle analysis, western blot for cyclin A/Rb/erbB2 phosphorylation Oncogene Medium 16007173
2001 DAL-1 interacts with ERM proteins and βII-spectrin (similar to merlin) but not SCHIP-1 (a merlin-specific interactor); DAL-1 suppresses cell proliferation in meningioma cells but not in schwannoma cells, indicating cell-type-specific growth regulation. Co-immunoprecipitation, proliferation assay (cell counting) Neurobiology of disease Medium 11300722
2002 Re-expression of DAL-1 in MCF-7 breast cancer cells suppresses growth (partly via apoptosis induction) and increases cell attachment to multiple extracellular matrices. Constitutive and inducible DAL-1 expression, cell growth assays, apoptosis assays, adhesion assays to ECM substrates International journal of cancer Medium 12115567
2007 Protein 4.1B interacts with p55 and sodium bicarbonate cotransporter 1 (NBC1) in the basolateral membrane of renal S1-S2 proximal tubules; GST pull-down and co-immunoprecipitation from kidney lysates confirmed a trimeric complex (NBC1-4.1B-p55). Co-immunoprecipitation from kidney lysates, GST pull-down, immunohistochemistry co-localization The journal of histochemistry and cytochemistry Medium 17712176
2019 The FERM domain of 4.1B interacts with the first 13 amino acids (P13) of the EGFR intracellular juxtamembrane segment; 4.1B binding inhibits EGFR dimerization and autophosphorylation, thereby suppressing EGFR/MAPK/ERK1/2 and PI3K/AKT signaling and inhibiting cancer cell proliferation. Co-immunoprecipitation, immunofluorescence colocalization, domain-mapping constructs, EGFR phosphorylation/dimerization assays, proliferation assays in GC cell lines and MEFs Cell communication and signaling Medium 31492173
2015 DAL-1 directly binds HSPA5 (GRP78/BiP), regulates its expression, and thereby suppresses EMT markers (E-cadherin, β-catenin, Vimentin, N-cadherin) and inhibits lung cancer cell migration and invasion; additionally, DAL-1 binds E-cadherin promoter to regulate its transcription. Co-immunoprecipitation, chromatin immunoprecipitation (direct E-cadherin promoter binding), EMT marker western blot, migration/invasion assays Journal of experimental & clinical cancer research Medium 25609022
2021 DAL-1/4.1B promotes exosome uptake by lung cancer cells by upregulating HSPG2 (heparan sulfate proteoglycan 2); HSPG2 knockdown abolishes the enhanced exosome uptake caused by DAL-1/4.1B overexpression. Overexpression/knockdown of DAL-1/4.1B, HSPG2 siRNA, vesicle uptake inhibitor panel, fluorescent exosome uptake assay Molecular and cellular biochemistry Low 34657240
2016 EPB41L3 overexpression suppresses ESCC cell invasion and migration and downregulates MMP2 and MMP9 expression; knockdown has the opposite effect. Overexpression plasmid and siRNA knockdown, transwell invasion/wound-healing assays, western blot for MMP2/MMP9/p-AKT Cell biochemistry and function Low 26916087
2000 Protein 4.1B is localized specifically at the plasma membrane in regions of cell-cell contact; it contains functional spectrin-actin binding and NuMA-binding domains subject to regulated alternative splicing (spectrin-actin domain present only in muscle isoforms); focal high expression occurs in select neuronal populations including Purkinje cells and hippocampal pyramidal neurons. In situ hybridization, immunofluorescence, Western blot, alternative splicing characterization The Journal of biological chemistry Medium 10652311
2010 Microcell-mediated chromosome 18 transfer suppressed ovarian cancer neoplasia; EPB41L3 re-expression in 3D spheroids caused growth suppression and induced apoptosis, identifying EPB41L3 as the chromosome 18 tumor suppressor gene responsible for neoplastic suppression. Microcell-mediated chromosome transfer, gene expression microarray, EPB41L3 reconstitution in 3D spheroid model, transmission/scanning electron microscopy, apoptosis assays Neoplasia Medium 20651987
2016 4.1B knockout in SV40T-immortalized MEFs is sufficient for malignant transformation: 4.1B-null iMEFs form tumors in nude mice (desmoid-type), display nuclear β-catenin accumulation, E-cadherin downregulation, and ERK/AKT activation; 4.1B interacts with E-cadherin in MEF cells. 4.1B-null iMEF transformation assay, xenograft in nude mice, western blot pathway analysis, co-immunoprecipitation (4.1B–E-cadherin) Molecular carcinogenesis Medium 27312663
2011 miR-223, induced by the transcription factor Twist, posttranscriptionally downregulates EPB41L3 expression by directly targeting its 3'-UTR, thereby promoting gastric cancer cell migration and invasion. Luciferase reporter assay (3'-UTR targeting), qRT-PCR, western blot, migration/invasion assays, miR-223 transfection Molecular cancer research : MCR Medium 21628394

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Molecular cancer research : MCR 325 21628394
2002 Direct association of TSLC1 and DAL-1, two distinct tumor suppressor proteins in lung cancer. Cancer research 163 12234973
2015 MicroRNA-223 delivered by platelet-derived microvesicles promotes lung cancer cell invasion via targeting tumor suppressor EPB41L3. Molecular cancer 156 25881295
2000 Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early event in the pathogenesis of meningiomas. Human molecular genetics 151 10888600
2000 Merlin, DAL-1, and progesterone receptor expression in clinicopathologic subsets of meningioma: a correlative immunohistochemical study of 175 cases. Journal of neuropathology and experimental neurology 139 11079777
2000 Molecular and functional characterization of protein 4.1B, a novel member of the protein 4.1 family with high level, focal expression in brain. The Journal of biological chemistry 116 10652311
2003 Protein 4.1B associates with both Caspr/paranodin and Caspr2 at paranodes and juxtaparanodes of myelinated fibres. The European journal of neuroscience 114 12542678
2004 DAL-1/4.1B tumor suppressor interacts with protein arginine N-methyltransferase 3 (PRMT3) and inhibits its ability to methylate substrates in vitro and in vivo. Oncogene 96 15334060
2010 Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adapter protein 4.1B. The Journal of neuroscience : the official journal of the Society for Neuroscience 93 20164332
1987 Membrane skeletal alterations during in vivo mouse red cell aging. Increase in the band 4.1a:4.1b ratio. The Journal of clinical investigation 85 3805278
2011 Characterization of the axon initial segment (AIS) of motor neurons and identification of a para-AIS and a juxtapara-AIS, organized by protein 4.1B. BMC biology 79 21958379
2007 Downregulation of TSLC1 and DAL-1 expression occurs frequently in breast cancer. Breast cancer research and treatment 74 17260099
2011 Aberrant expression of tumor suppressors CADM1 and 4.1B in invasive lesions of primary breast cancer. Breast cancer (Tokyo, Japan) 68 21526423
2006 Promoter hypermethylation of the potential tumor suppressor DAL-1/4.1B gene in renal clear cell carcinoma. International journal of cancer 66 16152585
2007 Protein 4.1B suppresses prostate cancer progression and metastasis. Proceedings of the National Academy of Sciences of the United States of America 62 17640904
2004 The MADS-box gene DAL1 is a potential mediator of the juvenile-to-adult transition in Norway spruce (Picea abies). The Plant journal : for cell and molecular biology 59 15500470
2000 Type II brain 4.1 (4.1B/KIAA0987), a member of the protein 4.1 family, is localized to neuronal paranodes. Brain research. Molecular brain research 59 11146105
2001 The protein 4.1 tumor suppressor, DAL-1, impairs cell motility, but regulates proliferation in a cell-type-specific fashion. Neurobiology of disease 58 11300722
2002 Suppression of growth and increased cellular attachment after expression of DAL-1 in MCF-7 breast cancer cells. International journal of cancer 55 12115567
2006 The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing apoptosis in MCF-7 breast cancer cells. Molecular cancer 52 16420693
2011 Protein 4.1B contributes to the organization of peripheral myelinated axons. PloS one 51 21966409
2011 The cytoskeletal adaptor protein band 4.1B is required for the maintenance of paranodal axoglial septate junctions in myelinated axons. The Journal of neuroscience : the official journal of the Society for Neuroscience 49 21632923
2017 LINC00052 upregulates EPB41L3 to inhibit migration and invasion of hepatocellular carcinoma by binding miR-452-5p. Oncotarget 46 28969024
2012 The 4.1B cytoskeletal protein regulates the domain organization and sheath thickness of myelinated axons. Glia 46 23109359
2009 SynCAM1 recruits NMDA receptors via protein 4.1B. Molecular and cellular neurosciences 46 19796685
2015 HPV33 DNA methylation measurement improves cervical pre-cancer risk estimation of an HPV16, HPV18, HPV31 and \textit{EPB41L3} methylation classifier. Cancer biomarkers : section A of Disease markers 45 26406956
2010 Microcell-mediated chromosome transfer identifies EPB41L3 as a functional suppressor of epithelial ovarian cancers. Neoplasia (New York, N.Y.) 45 20651987
2005 An interaction between {alpha}v{beta}8 integrin and Band 4.1B via a highly conserved region of the Band 4.1 C-terminal domain. Proceedings of the National Academy of Sciences of the United States of America 45 16157875
2005 Inactivation patterns of NF2 and DAL-1/4.1B (EPB41L3) in sporadic meningioma. Cancer genetics and cytogenetics 45 16213361
2002 Differential involvement of protein 4.1 family members DAL-1 and NF2 in intracranial and intraspinal ependymomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 44 12011257
1988 Correlation between protein 4.1a/4.1b ratio and erythrocyte life span. Biochimica et biophysica acta 42 3179290
2021 MADS-box transcription factors MADS11 and DAL1 interact to mediate the vegetative-to-reproductive transition in pine. Plant physiology 37 34618133
2006 Protein 4.1B/differentially expressed in adenocarcinoma of the lung-1 functions as a growth suppressor in meningioma cells by activating Rac1-dependent c-Jun-NH(2)-kinase signaling. Cancer research 35 16707455
1991 The allantoinase (DAL1) gene of Saccharomyces cerevisiae. Yeast (Chichester, England) 34 1803816
2014 Tumor suppressor role of protein 4.1B/DAL-1. Cellular and molecular life sciences : CMLS 33 25183197
2002 The 4.1/ezrin/radixin/moesin domain of the DAL-1/Protein 4.1B tumour suppressor interacts with 14-3-3 proteins. The Biochemical journal 33 11996670
2005 Loss of the putative tumor suppressor band 4.1B/Dal1 gene is dispensable for normal development and does not predispose to cancer. Molecular and cellular biology 32 16260618
2008 Potential role of EPB41L3 (protein 4.1B/Dal-1) as a target for treatment of advanced prostate cancer. Expert opinion on therapeutic targets 31 18554153
2007 Evidence for protein 4.1B acting as a metastasis suppressor. Journal of cell science 31 17264155
2004 Immunolocalization of protein 4.1B/DAL-1 during neoplastic transformation of mouse and human intestinal epithelium. Histochemistry and cell biology 31 15517334
2000 Comparison of mRNA and protein levels of four members of the protein 4.1 family: the type II brain 4.1/4.1B/KIAA0987 is the most predominant member of the protein 4.1 family in rat brain. Gene 30 10806359
2009 A Golgi-associated protein 4.1B variant is required for assimilation of proteins in the membrane. Journal of cell science 29 19299464
2005 Membrane localization of the U2 domain of Protein 4.1B is necessary and sufficient for meningioma growth suppression. Oncogene 28 15688033
2005 The tumor suppressor DAL-1/4.1B modulates protein arginine N-methyltransferase 5 activity in a substrate-specific manner. Biochemical and biophysical research communications 28 15737618
2012 Loss of expression of the differentially expressed in adenocarcinoma of the lung (DAL-1) protein is associated with metastasis of non-small cell lung carcinoma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 27 22782504
2004 Allele-specific loss of heterozygosity at the DAL-1/4.1B (EPB41L3) tumor-suppressor gene locus in the absence of mutation. Genes, chromosomes & cancer 27 15138999
2019 Methylation of HPV 16 and EPB41L3 in oral gargles: Associations with oropharyngeal cancer detection and tumor characteristics. International journal of cancer 24 31304592
2015 Prolonged re-expression of the hypermethylated gene EPB41L3 using artificial transcription factors and epigenetic drugs. Epigenetics 24 25830725
2021 Insight into Codon Utilization Pattern of Tumor Suppressor Gene EPB41L3 from Different Mammalian Species Indicates Dominant Role of Selection Force. Cancers 23 34205890
2010 Arabidopsis DAL1 and DAL2, two RING finger proteins homologous to Drosophila DIAP1, are involved in regulation of programmed cell death. Plant cell reports 23 20972793
2003 Protein 4.1B in mouse islets of Langerhans and beta-cell tumorigenesis. Histochemistry and cell biology 22 14574582
2015 DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer. Journal of experimental & clinical cancer research : CR 20 25609022
2011 β8 integrin and band 4.1B cooperatively regulate morphogenesis of the embryonic heart. Developmental dynamics : an official publication of the American Association of Anatomists 20 21181944
2010 Structural basis of tumor suppressor in lung cancer 1 (TSLC1) binding to differentially expressed in adenocarcinoma of the lung (DAL-1/4.1B). The Journal of biological chemistry 20 21131357
2009 Frequent concomitant epigenetic silencing of the stress-responsive tumor suppressor gene CADM1, and its interacting partner DAL-1 in nasal NK/T-cell lymphoma. International journal of cancer 20 19115211
2004 Immunohistochemical study of protein 4.1B in the normal and W/W(v) mouse seminiferous epithelium. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20 15150285
2018 Associations of human gene EPB41L3 DNA methylation and cervical intraepithelial neoplasia in women living with HIV-1 in Africa. AIDS (London, England) 19 30005021
2016 Assembly of juxtaparanodes in myelinating DRG culture: Differential clustering of the Kv1/Caspr2 complex and scaffolding protein 4.1B. Glia 19 26840208
2016 Epb41l3 suppresses esophageal squamous cell carcinoma invasion and inhibits MMP2 and MMP9 expression. Cell biochemistry and function 19 26916087
2007 Expression and DNA methylation patterns of Tslc1 and Dal-1 genes in hepatocellular carcinomas induced by N-nitrosodiethylamine in rats. Cancer science 19 17428255
2005 Protein 4.1B expression is induced in mammary epithelial cells during pregnancy and regulates their proliferation. Oncogene 19 16007173
2017 DAL-1 attenuates epithelial to mesenchymal transition and metastasis by suppressing HSPA5 expression in non-small cell lung cancer. Oncology reports 17 29048640
2009 Expression of the tumor suppressor genes NF2, 4.1B, and TSLC1 in canine meningiomas. Veterinary pathology 17 19429976
2013 A 130-kDa protein 4.1B regulates cell adhesion, spreading, and migration of mouse embryo fibroblasts by influencing actin cytoskeleton organization. The Journal of biological chemistry 16 24381168
2007 Interaction of membrane skeletal protein, protein 4.1B and p55, and sodium bicarbonate cotransporter1 in mouse renal S1-S2 proximal tubules. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 16 17712176
2004 Putative tumor suppressor protein 4.1B is differentially expressed in kidney and brain via alternative promoters and 5' alternative splicing. Biochimica et biophysica acta 16 15488987
2020 LncRNA MAGI2-AS3 Affects Cell Invasion and Migration of Cervical Squamous Cell Carcinoma (CSCC) via Sponging miRNA-233/EPB41L3 Axis. Cancer management and research 15 32581592
2019 miR-452 promotes the development of gastric cancer via targeting EPB41L3. Pathology, research and practice 15 31734055
2005 Mutational analysis of the DAL-1/4.1B tumour-suppressor gene locus in meningiomas. International journal of molecular medicine 15 16142420
2004 Immunoelectron microscopic localization of protein 4.1B in proximal S1 and S2 tubules of rodent kidneys. Medical electron microscopy : official journal of the Clinical Electron Microscopy Society of Japan 15 15057604
2004 Disruption of 14-3-3 binding does not impair Protein 4.1B growth suppression. Oncogene 15 15116094
2016 Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer. Scientific reports 14 26923709
2007 Hypermethylation of the Dal-1 gene in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats. Molecular carcinogenesis 11 17415786
2005 Evolutionarily conserved coupling of transcription and alternative splicing in the EPB41 (protein 4.1R) and EPB41L3 (protein 4.1B) genes. Genomics 11 16242908
2004 Immunolocalization of protein 4.1B in the rat digestive system. Journal of molecular histology 9 15503808
2021 DAL-1/4.1B promotes the uptake of exosomes in lung cancer cells via Heparan Sulfate Proteoglycan 2 (HSPG2). Molecular and cellular biochemistry 8 34657240
2015 The targeted inhibitory effects of human amniotic fluid stem cells carrying CXCR4 promoter and DAL-1 on non-small cell lung carcinoma growth. Gene therapy 8 26280082
2001 Cis-acting sites contributing to expression of divergently transcribed DAL1 and DAL4 genes in S. cerevisiae: a word of caution when correlating cis-acting sequences with genome-wide expression analyses. Current genetics 8 11409177
2022 HDAC10 Inhibits Cervical Cancer Progression through Downregulating the HDAC10-microRNA-223-EPB41L3 Axis. Journal of oncology 7 35075362
2022 Methylation of HPV16 and EPB41L3 in oral gargles and the detection of early and late oropharyngeal cancer. Cancer medicine 7 35619332
2019 4.1B suppresses cancer cell proliferation by binding to EGFR P13 region of intracellular juxtamembrane segment. Cell communication and signaling : CCS 7 31492173
2019 Mutation and Expression of a Candidate Tumor Suppressor Gene EPB41L3 in Gastric and Colorectal Cancers. Pathology oncology research : POR 7 31828581
2019 Promoter-associated DNA methylation & expression profiling of genes (FLT 3, EPB41L3 & SFN) in patients with oral squamous cell carcinoma in the Khasi & Jaintia population of Meghalaya, India. The Indian journal of medical research 7 32048621
2016 Knockout of 4.1B triggers malignant transformation in SV40T-immortalized mouse embryo fibroblast cells. Molecular carcinogenesis 7 27312663
2015 DAL-1/4.1B contributes to epithelial-mesenchymal transition via regulation of transforming growth factor-β in lung cancer cell lines. Molecular medicine reports 7 26300315
2019 Pivotal roles of protein 4.1B/DAL‑1, a FERM‑domain containing protein, in tumor progression (Review). International journal of oncology 6 31545421
2018 MicroRNA-26a regulates ANXA1, rather than DAL-1, in the development of lung cancer. Oncology letters 6 29552220
2009 Dispensable role of protein 4.1B/DAL-1 in rodent adrenal medulla regarding generation of pheochromocytoma and plasmalemmal localization of TSLC1. Biochimica et biophysica acta 6 19321127
2023 Expression and hypermethylation of JAM and EPB41L3 in cervical squamous cell carcinoma: Clinical significance and applications. Histology and histopathology 5 38213260
2022 Over-expression of EPB41L3 promotes apoptosis of human cervical carcinoma cells through PI3K/AKT signaling. Acta biochimica Polonica 5 35569139
2019 Protein 4.1B Suppresses Tumor Metastasis by Regulating Epithelial-mesenchymal Transition Progression in Melanoma Cells. International journal of medical sciences 5 31171904
2018 Ablation of cytoskeletal scaffolding proteins, Band 4.1B and Whirlin, leads to cerebellar purkinje axon pathology and motor dysfunction. Journal of neuroscience research 5 30447021
2004 Protein 4.1B localizes on unmyelinated axonal membranes in the mouse enteric nervous system. Neuroscience letters 5 15265581
2025 The MADS-box transcription factor DAL1 links age to reproductive development through regulation of LEAFY homologs in conifer. Plant physiology 4 40208195
2024 EPB41L3 Inhibits the Progression of Cervical Cancer Via the ERK/p38 MAPK Signaling Pathway. Molecular biotechnology 4 38907071
2024 DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging. Tumour virus research 3 38960143
2024 The MADS-domain transcription factor DAL10 is a direct target of putative DAL1-mediated age pathway in conifers. Journal of experimental botany 3 39082682
2023 Exploring the Diagnostic Potential of EPB41L3 Methylation in Cervical Cancer and Precancerous Lesions: A Systematic Review and Meta-Analysis. Gynecologic and obstetric investigation 3 38081153
2023 Performance of Human Gene EPB41L3 and HPV 16/18 Viral DNA Methylation to Triage hrHPV-Positive Women. Vaccines 3 38250859
2019 [Corrigendum] Pivotal roles of protein 4.1B/DAL‑1, a FERM‑domain containing protein, in tumor progression (Review). International journal of oncology 2 31814035