Affinage

TLE1

Transducin-like enhancer protein 1 · UniProt Q04724

Length
770 aa
Mass
83.2 kDa
Annotated
2026-04-28
100 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TLE1 is a non-DNA-binding transcriptional corepressor that serves as a nexus for integrating diverse developmental, inflammatory, and oncogenic signals by bridging sequence-specific transcription factors to chromatin-modifying machinery. Its C-terminal WD40 β-propeller domain engages WRPW-motif partners (e.g., HES1) and Eh1-motif partners (e.g., FOXG1, Engrailed) through structurally distinct binding surfaces, and once recruited to target promoters it silences genes such as E-cadherin, Cyclin D1, and glucagon by recruiting histone deacetylase activity (PMID:12057191, PMID:18611861, PMID:25446087, PMID:24487024). TLE1 repressor function is positively regulated by CK2 phosphorylation at Ser-239, which promotes nuclear retention and anti-neurogenic activity, and by cofactor-activated phosphorylation at Ser-286/289/298 that strengthens chromatin association, whereas Ras-ERK-mediated phosphorylation causes nuclear exclusion and loss of repression (PMID:15367661, PMID:19956621, PMID:28192406). In vivo, TLE1 loss produces chronic NF-κB-driven inflammation and accelerated tumor growth, and its promoter is epigenetically silenced by CpG hypermethylation in hematologic malignancies, establishing TLE1 as a context-dependent tumor suppressor in myeloid leukemia and lymphoma (PMID:26831087, PMID:18519670, PMID:18258796).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Establishing that mammalian TLE1 directly contacts HES1 via the WRPW motif resolved whether the Drosophila Groucho–Hairy corepressor mechanism was conserved in mammals and defined the founding protein-protein interaction mode.

    Evidence Yeast two-hybrid and GST pull-down with HES-1 and TLE1

    PMID:8687460

    Open questions at the time
    • Binding affinity not quantified
    • Functional repression by the complex not demonstrated in this study
    • Other WRPW-containing partners not tested
  2. 1996 Medium

    Demonstrating that phosphorylated TLE1 isoforms preferentially associate with nuclei during neural differentiation first linked post-translational modification to TLE1 subcellular regulation.

    Evidence Subcellular fractionation and SDS-PAGE of P19 cell differentiation lysates

    PMID:8713081

    Open questions at the time
    • Kinase identity unknown
    • Phosphorylation sites not mapped
    • Causality between phosphorylation and nuclear retention not tested
  3. 2002 High

    The 1.6 Å crystal structure of the TLE1 WD40 domain revealed a seven-bladed β-propeller with separate WRPW- and Eh1-binding surfaces, providing the structural framework for understanding how one corepressor engages multiple transcription-factor classes.

    Evidence X-ray crystallography with functional mutation mapping in C. elegans UNC-37

    PMID:12057191

    Open questions at the time
    • Full-length TLE1 structure not determined
    • Eh1 peptide-bound co-crystal not yet obtained in this study
    • Oligomerization interface not resolved
  4. 2002 Medium

    Identifying the gp130 cytoplasmic domain as a TLE1 Q-domain interactor extended TLE1 function beyond classical transcription-factor partnerships to cytokine signaling scaffolds.

    Evidence Yeast two-hybrid, GST pull-down, and co-immunoprecipitation with gp130 truncations

    PMID:12030375

    Open questions at the time
    • Functional consequence of gp130–TLE1 interaction on cytokine signaling not shown
    • Endogenous complex not validated
    • Specificity among TLE family members not tested
  5. 2003 Medium

    Discovery that the oncoprotein Qin recruits TLE1 through a WRPW motif and that this interaction correlates with transformation linked TLE1 for the first time to an oncogenic pathway.

    Evidence Yeast two-hybrid screen, mammalian two-hybrid, and chicken embryo fibroblast transformation assay

    PMID:12660810

    Open questions at the time
    • Whether TLE1 is required for Qin transformation not tested by loss-of-function
    • Downstream target genes not identified
    • Relevance to human cancer unknown
  6. 2004 High

    Mapping CK2-mediated phosphorylation of TLE1 at Ser-239 as necessary for nuclear retention and anti-neurogenic repression established the first site-specific mechanism controlling TLE1 activity in a developmental context.

    Evidence In vivo phosphorylation, S239A/S239E mutagenesis, cortical progenitor differentiation assay

    PMID:15367661

    Open questions at the time
    • Upstream signals activating CK2 in progenitors not identified
    • Whether CK2 phosphorylation also affects non-neuronal functions unknown
    • Interaction with chromatin not directly assayed
  7. 2004 High

    Showing that CaMKIIδ-activated PARP-1 dismisses TLE1 from HES1-bound promoters, switching HES1 from repressor to activator, revealed a regulated corepressor-exchange mechanism at neurogenic genes.

    Evidence Co-IP, ChIP, reporter assays, and dominant-negative CaMKII constructs

    PMID:15607978

    Open questions at the time
    • Direct PARP-1 modification of TLE1 not demonstrated
    • Genome-wide scope of this switch unknown
    • Whether this mechanism operates outside neurogenesis not tested
  8. 2008 High

    Structure-guided L743F mutagenesis in the WD40 domain selectively ablated WRPW binding (HES1) without affecting Eh1 binding (FoxG1, Engrailed), functionally separating two corepressor recruitment modes and showing WRPW interaction is specifically required for anti-neurogenic activity.

    Evidence Site-directed mutagenesis, co-immunoprecipitation, cortical progenitor assay

    PMID:18611861

    Open questions at the time
    • Eh1-specific mutation complementing L743F not generated
    • Effect on chromatin modification not tested
    • In vivo validation lacking
  9. 2008 High

    Demonstrating that TLE1 is epigenetically silenced by promoter hypermethylation in B-cell lymphoma and AML, and that its re-expression inhibits growth and represses Cyclin D1, CSF1R, and HES1, established TLE1 as a bona fide tumor suppressor in hematologic malignancies.

    Evidence Bisulfite sequencing, colony formation, nude mouse xenograft, shRNA, gene expression profiling

    PMID:18258796 PMID:18519670

    Open questions at the time
    • Whether methylation-mediated silencing occurs in solid tumors not addressed
    • Direct promoter occupancy at Cyclin D1 not shown by ChIP
    • Patient outcome correlation not provided
  10. 2009 High

    Identification of cofactor-activated phosphorylation at Ser-286/289/298 by mass spectrometry, induced upon DNA-binding partner interaction, revealed a feed-forward mechanism whereby partner recruitment strengthens TLE1–chromatin association independently of DNA targeting.

    Evidence Mass spectrometry, site-directed mutagenesis, cortical progenitor differentiation assay

    PMID:19956621

    Open questions at the time
    • Kinase responsible for cofactor-activated phosphorylation not identified
    • Whether this mechanism is universal across all TLE1 partners unknown
    • Chromatin substrate specificity not defined
  11. 2010 High

    Showing that TLE1 co-occupies ribosomal RNA gene loci with Runx2 and represses rRNA transcription linked the corepressor to ribosome biogenesis and global translational control, extending its roles beyond mRNA-encoding gene regulation.

    Evidence Co-IP, ChIP at rDNA loci, siRNA knockdown, rRNA transcription and cell proliferation assays

    PMID:20160071

    Open questions at the time
    • Mechanism of TLE1-mediated histone deacetylation at rDNA not elucidated
    • Whether rRNA repression contributes to tumor suppression unknown
    • Mitotic bookmarking mechanism not resolved
  12. 2014 Medium

    Demonstrating that TLE1 is the predominant Groucho family member in β-cells and represses α-cell genes (glucagon, Arx) established TLE1 as a determinant of endocrine cell identity in the pancreas.

    Evidence Grg3 haploinsufficient mouse, ectopic expression in pancreatic cell lines, insulin secretion assay

    PMID:24487024

    Open questions at the time
    • β-cell-specific TLE1 knockout not performed
    • Direct TLE1 ChIP at glucagon/Arx promoters not shown
    • Human β-cell relevance not demonstrated
  13. 2016 High

    Conditional Tle1 knockout mice exhibiting chronic NF-κB hyperactivation, elevated inflammatory cytokines, and accelerated tumor growth provided definitive in vivo evidence that TLE1 is a physiological brake on innate immune signaling.

    Evidence Conditional Tle1 KO mouse, macrophage stimulation, cytokine ELISA, NF-κB phospho-blot, melanoma xenograft

    PMID:26831087

    Open questions at the time
    • Direct mechanism of NF-κB inhibition (chromatin vs. cytoplasmic sequestration) not resolved
    • Contribution of individual TLE1-partner interactions to inflammation unknown
    • Adaptive immune cell phenotype not characterized
  14. 2017 High

    Identifying Ras-ERK-mediated phosphorylation as the signal that excludes TLE1 from the nucleus resolved the long-standing question of how oncogenic signaling inactivates this corepressor, and showed that an unphosphorylatable TLE1 mutant blocks H-Ras-driven transformation.

    Evidence Phosphorylation assays, nuclear exclusion imaging, Drosophila transgenic, mouse xenograft

    PMID:28192406

    Open questions at the time
    • Specific ERK phosphorylation sites on TLE1 not mapped
    • Relationship to CK2 and cofactor-activated phosphorylation not integrated
    • Whether nuclear exclusion targets TLE1 for degradation unknown
  15. 2017 High

    Demonstrating that TLE1 partners with ZEB1 to co-occupy the E-cadherin promoter and impose HDAC-dependent silencing unified TLE1's roles in EMT promotion and anoikis resistance through a single transcription-factor partnership.

    Evidence ChIP, co-IP, siRNA, forced expression, and xenograft tumorigenicity

    PMID:29069783

    Open questions at the time
    • Which HDAC isoform is recruited not identified
    • Genome-wide ZEB1-TLE1 co-occupancy not mapped
    • Structural basis of TLE1–ZEB1 interaction unknown
  16. 2021 Medium

    Identifying a unique N-terminal phosphorylation site that distinguishes TLE1 from TLE3 functional activity clarified how paralog-specific post-translational modifications diversify Groucho family member output.

    Evidence Mutagenesis, paclitaxel sensitivity assay, and adipocyte differentiation assay

    PMID:33571907

    Open questions at the time
    • Kinase responsible not identified
    • Phosphorylation site not mapped to a specific residue
    • In vivo relevance not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the HDAC isoform(s) directly recruited by TLE1, the full-length oligomeric structure, the precise ERK phosphorylation sites mediating nuclear exclusion, and whether TLE1's anti-inflammatory and tumor-suppressive activities can be pharmacologically enhanced.
  • Full-length TLE1 structure not determined
  • HDAC isoform specificity unresolved
  • ERK phosphorylation sites not mapped
  • No therapeutic-grade TLE1-modulating compound reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0042393 histone binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 2
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-1266738 Developmental Biology 3 R-HSA-4839726 Chromatin organization 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2
Partners
AESFOXG1GP130HES1HESX1NOD2RUNX2ZEB1
Complex memberships
FOXG1–TLE1 corepressor complexHES1–TLE1 corepressor complexRunx2–TLE1 corepressor complexZEB1–TLE1 corepressor complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 TLE1 directly interacts with the WRPW motif of HES-1 (a mammalian Hairy-like protein), as demonstrated by yeast two-hybrid assay and GST pull-down assays, establishing a conserved Groucho/TLE–Hairy/HES interaction in mammals. Yeast two-hybrid assay; GST fusion protein pull-down assay Biochemical and biophysical research communications High 8687460
1996 Groucho/TLE1 proteins are phosphorylated, and more slowly migrating (higher molecular mass) phosphorylated forms associate more strongly with the nuclear compartment; these higher-mass TLE1 forms are induced during neural determination of P19 cells, implicating phosphorylation in nuclear function. Subcellular fractionation; SDS-PAGE mobility shift; immunoblotting; P19 differentiation model The Biochemical journal Medium 8713081
2002 Crystal structure of the C-terminal WD40 repeat domain of human TLE1 was determined to 1.6 Å, revealing a seven-bladed β-propeller; the structure identifies protein-protein interaction sites, including an induced-fit binding site for Eh1 (Engrailed-homology 1) domain transcription factors, and confirms structural relationship to yeast Tup1 corepressor. X-ray crystallography at 1.6 Å resolution; missense mutation analysis in C. elegans UNC-37 Structure High 12057191
2002 TLE1 interacts with the intracellular region of gp130 (the shared IL-6 family cytokine signal transducer) through its Q domain, with the membrane-proximal Box1/Box2-containing region of gp130 being essential; demonstrated by yeast two-hybrid, GST pull-down, and co-immunoprecipitation. Yeast two-hybrid; GST pull-down; co-immunoprecipitation Molecular and cellular biochemistry Medium 12030375
2003 TLE1 was identified as a binding partner of the oncoprotein Qin (a winged helix transcription factor) via yeast two-hybrid screen; TLE1 binding requires a WRPW motif and correlates with Qin-induced transformation of chicken embryo fibroblasts; Qin binding induces phosphorylation of TLE1. Yeast two-hybrid screen; mammalian two-hybrid; transformation assay in chicken embryo fibroblasts Oncogene Medium 12660810
2003 TLE1 was identified as an activation function-1 (AF-1) cofactor of the orphan nuclear receptor ERRγ; direct interaction was demonstrated by phage display biopanning and pull-down assay; surprisingly, TLE1 functioned as a coactivator (not repressor) of ERRγ in reporter gene assays. Phage display library biopanning; GST pull-down; reporter gene assay Biochemical and biophysical research communications Medium 14651967
2004 CaMKIIδ-mediated activation triggers PARP-1, a component of the Groucho/TLE1 corepressor complex, causing dismissal of the TLE corepressor complex from HES1-regulated promoters; CaMKIIδ also phosphorylates HES1 to permit coactivator recruitment, switching HES1 from a TLE1-dependent repressor to an activator of neurogenic gene programs. Co-immunoprecipitation; chromatin immunoprecipitation (ChIP); reporter assays; pharmacological CaMKII activation; dominant-negative constructs Cell High 15607978
2004 Protein kinase CK2 phosphorylates TLE1 at serine 239 within the conserved CcN domain; this phosphorylation is required for TLE1 nuclear association, transcription repression activity, and its ability to inhibit cortical neural progenitor differentiation into neurons (mutation S239A reduces antineurogenic activity; S239E does not). In vivo phosphorylation assay; site-directed mutagenesis; cortical neural progenitor differentiation assay; immunocytochemistry Molecular and cellular biology High 15367661
2005 TLE1 is expressed in postmitotic neurons of the adult rat brain, and its immunoreactivity is detected not only in nuclei but also in apical dendritic shafts of neocortical layer III/V pyramidal cells and Purkinje cell dendrites, indicating an unexpected extranuclear localization in differentiated neurons. Immunohistochemistry; confocal microscopy in adult rat brain sections Brain research. Molecular brain research Medium 16081186
2008 TLE1 (and TLE4) function as tumor suppressors in myeloid leukemia: shRNA knockdown of TLE1 rescues AML1-ETO-expressing cells from cell-cycle arrest and apoptosis, while forced TLE1 expression causes apoptosis; genetic epistasis in zebrafish confirms cooperation between TLE loss and AML1-ETO in hematopoietic blast accumulation. shRNA knockdown; forced expression; cell proliferation/apoptosis assays; zebrafish genetic epistasis Blood High 18258796
2008 Point mutation L743F in the WD40 domain of TLE1 selectively blocks binding to Hes1 (WRPW motif) without disrupting binding to Engrailed1, FoxG1 (Eh1 motif), or Tcf3; this WRPW-binding is specifically required for TLE1-mediated inhibition of cortical neuron differentiation. Site-directed mutagenesis; co-immunoprecipitation; cortical neural progenitor differentiation assay The Journal of biological chemistry High 18611861
2008 TLE1 undergoes promoter CpG island hypermethylation-associated silencing in diffuse large B-cell lymphoma and AML; reintroduction of TLE1 in hypermethylated cells causes growth inhibition in colony and xenograft assays, with effects mediated through transcriptional repression of Cyclin D1, CSF1R, and HES1. Bisulfite sequencing; colony formation assay; nude mouse xenograft; shRNA knockdown; gene expression analysis Cancer research High 18519670
2009 Cofactor-activated phosphorylation of TLE1 at Ser-286 (and nearby Ser-289, Ser-298) within the SP domain, induced by interaction with DNA-binding partners (e.g., Hes1), strengthens TLE1 chromatin association and is required for its anti-neurogenic activity; mutations at these sites impair cofactor-activated phosphorylation and weaken chromatin binding without disrupting partner interaction or DNA recruitment. Site-directed mutagenesis; mass spectrometry; biochemistry; primary cortical neural progenitor culture; immunocytochemistry PloS one High 19956621
2010 TLE1 associates with ribosomal RNA genes during mitosis and interphase through physical interaction with Runx2; TLE1 depletion relieves Runx2-mediated repression of rRNA transcription, increases active histone modifications at rRNA gene loci, and leads to increased global protein synthesis and cell proliferation. Co-immunoprecipitation; ChIP; siRNA knockdown; ribosomal RNA transcription assay; cell proliferation assay Proceedings of the National Academy of Sciences of the United States of America High 20160071
2010 TLE1 and TLE3 interact with HESX1 and can repress PROP1 transcription both in the presence and absence of HESX1 via direct protein-protein interaction; TLE1 and TLE3 show similar repressive efficiencies; constitutive HESX1 expression in thyrotrophs and gonadotrophs suppresses terminal differentiation in transgenic mice. Co-immunoprecipitation; reporter gene assay; transgenic mouse overexpression Molecular endocrinology Medium 20181723
2011 TLE1 physically interacts with NOD2 (identified by yeast two-hybrid and confirmed by co-immunoprecipitation); TLE1 and NOD2 co-localize around the nuclear membrane; TLE1 inhibits NOD2-induced NF-κB activation in HEK293 cells, and TLE1 SNPs interact epistatically with NOD2 mutations in Crohn's disease susceptibility. Yeast two-hybrid; co-immunoprecipitation; co-localization; NF-κB reporter assay; genetic epistasis analysis Gastroenterology High 21699783
2012 TLE1 promotes anoikis resistance in breast cancer cells; TLE1 inhibits the Bit1 anoikis pathway by sequestering AES in the nucleus, reducing formation of the proapoptotic Bit1-AES cytoplasmic complex; cytoplasmic Bit1 causes nuclear TLE1 translocation to the cytoplasm and its degradation. Forced expression; siRNA knockdown; anoikis assay; subcellular fractionation; immunofluorescence; co-immunoprecipitation Molecular cancer research Medium 22952044
2012 TLE1 promotes neuronal survival in cerebellar granule neurons cooperatively with FoxG1; CK2 phosphorylation of TLE1 at Ser-239 and Ser-253 is required for its survival-promoting activity; PI3K-Akt signaling but not MEK-ERK or HDAC activity is required for TLE1-mediated neuroprotection. Ectopic expression; siRNA knockdown; pharmacological inhibitors; point mutant analysis; cerebellar granule neuron primary culture; cell viability assay The Journal of biological chemistry Medium 22354967
2014 TLE1 promotes epithelial-to-mesenchymal transition (EMT) in A549 lung cancer cells by transcriptionally repressing E-cadherin; TLE1 recruits histone deacetylase (HDAC) activity to the E-cadherin promoter; HDAC inhibitor TSA partially reverses TLE1-induced E-cadherin downregulation and cell migration. Forced expression; siRNA knockdown; cell migration assay; RT-PCR; ChIP; HDAC inhibitor treatment Biochemical and biophysical research communications Medium 25446087
2014 Grg1/TLE1 (the predominant Groucho in human β-cells) induces monohormonal β-cell identity and represses α-cell gene functions including glucagon and Arx expression; ectopic Grg3 in α-cells represses glucagon and, combined with Pdx1, induces glucose-responsive insulin secretion. Mouse genetic model (Grg3+/−); ectopic expression in pancreatic cell lines; gene expression profiling; insulin secretion assay Diabetes Medium 24487024
2016 Tle1-deficient mice display a chronic inflammatory phenotype with increased NF-κB phosphorylation and activation in macrophages, increased inflammatory cytokines in response to TLR agonists/LPS, decreased Hes1 expression, and accelerated melanoma xenograft growth; this establishes TLE1 as an in vivo negative regulator of NF-κB-mediated inflammation. Conditional Tle1 knockout mouse; macrophage stimulation assay; cytokine ELISA; NF-κB phosphorylation immunoblotting; xenograft tumor model Proceedings of the National Academy of Sciences of the United States of America High 26831087
2017 TLE1 is phosphorylated by Ras-ERK pathway activation, which excludes TLE1 from the nucleus and attenuates its transcriptional repressor function; unphosphorylatable TLE1 blocks oncogenic H-Ras phenotypes in human mammary cells in vitro and in vivo, while phosphomimetic TLE1 has minimal repressive effects. Phosphorylation assays; nuclear exclusion/localization imaging; reporter gene assay; Drosophila transgenic model; mouse xenograft Oncogene High 28192406
2017 TLE1 suppresses E-cadherin transcription by interacting with and recruiting ZEB1 to the E-cadherin promoter, imposing histone deacetylation and gene silencing; ZEB1 is required for TLE1-mediated anoikis resistance and tumorigenicity in lung cancer cells in vivo. ChIP; co-immunoprecipitation; siRNA; forced expression; xenograft tumorigenicity assay Oncotarget High 29069783
2017 The crystal structure of a stapled peptide inhibitor complexed with the TLE1 WD40 domain was solved; the WRPW epitope binds the WD40 β-propeller, and the constrained cycFWRPW peptide binds TLE1 with ~5-fold higher Kd than the acyclic peptide due to a small shift of one side chain. Co-crystal structure; isothermal titration calorimetry (ITC); thermal shift assay Chemistry High 28326635
2018 FOXG1 and TLE1 form a complex that directly targets and represses specific genes in glioblastoma-initiating cells, including negative regulators of NOTCH signaling such as CHAC1; ChIP-Seq identified 150 direct FOXG1 targets, several shared with TLE1. ChIP-Seq; RNA-Seq; co-immunoprecipitation (implied by complex characterization) Molecular oncology Medium 29316219
2021 A unique amino-terminal phosphorylation site present in TLE1 but absent from TLE3 confers distinct functional activity; mutating or reconstituting this site converts TLE1 activity toward TLE3-like behavior (and vice versa) in lung cancer drug sensitivity and adipocyte differentiation assays. Retroviral transduction; site-directed mutagenesis; paclitaxel sensitivity assay; adipocyte differentiation assay Biochemical and biophysical research communications Medium 33571907

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Activating the PARP-1 sensor component of the groucho/ TLE1 corepressor complex mediates a CaMKinase IIdelta-dependent neurogenic gene activation pathway. Cell 254 15607978
2009 TLE1 expression is not specific for synovial sarcoma: a whole section study of 163 soft tissue and bone neoplasms. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 164 19363472
2011 Immunohistochemical staining for TLE1 distinguishes synovial sarcoma from histologic mimics. American journal of clinical pathology 159 21571956
1996 Molecular interaction between TLE1 and the carboxyl-terminal domain of HES-1 containing the WRPW motif. Biochemical and biophysical research communications 130 8687460
2009 Prospective evaluation of TLE1 as a diagnostic immunohistochemical marker in synovial sarcoma. The American journal of surgical pathology 106 19809272
1993 Identification of esg, a genetic locus involved in cell-cell signaling during Myxococcus xanthus development. Journal of bacteriology 93 8253664
2010 TLE1 is a robust diagnostic biomarker for synovial sarcomas and correlates with t(X;18): analysis of 319 cases. European journal of cancer (Oxford, England : 1990) 82 20189377
2008 Loss of TLE1 and TLE4 from the del(9q) commonly deleted region in AML cooperates with AML1-ETO to affect myeloid cell proliferation and survival. Blood 78 18258796
2009 ESG: extended similarity group method for automated protein function prediction. Bioinformatics (Oxford, England) 77 19435743
1993 Molecular cloning and expression of mouse and human cDNA encoding AES and ESG proteins with strong similarity to Drosophila enhancer of split groucho protein. European journal of biochemistry 67 8365415
1995 The esg locus of Myxococcus xanthus encodes the E1 alpha and E1 beta subunits of a branched-chain keto acid dehydrogenase. Molecular microbiology 62 7565081
2016 Tle1 tumor suppressor negatively regulates inflammation in vivo and modulates NF-κB inflammatory pathway. Proceedings of the National Academy of Sciences of the United States of America 61 26831087
2005 Analysis of Esg1 expression in pluripotent cells and the germline reveals similarities with Oct4 and Sox2 and differences between human pluripotent cell lines. Stem cells (Dayton, Ohio) 61 16166252
2002 Crystal structure of the C-terminal WD40 repeat domain of the human Groucho/TLE1 transcriptional corepressor. Structure (London, England : 1993) 59 12057191
2006 Modelling transcriptional feedback loops: the role of Gro/TLE1 in Hes1 oscillations. Philosophical transactions. Series A, Mathematical, physical, and engineering sciences 58 16608701
2004 Phosphorylation of serine 239 of Groucho/TLE1 by protein kinase CK2 is important for inhibition of neuronal differentiation. Molecular and cellular biology 54 15367661
2006 Grg1 acts as a lung-specific oncogene in a transgenic mouse model. Cancer research 49 16452182
2008 Epigenetic inactivation of the Groucho homologue gene TLE1 in hematologic malignancies. Cancer research 47 18519670
1996 Affinity for the nuclear compartment and expression during cell differentiation implicate phosphorylated Groucho/TLE1 forms of higher molecular mass in nuclear functions. The Biochemical journal 47 8713081
2012 TLE1 is an anoikis regulator and is downregulated by Bit1 in breast cancer cells. Molecular cancer research : MCR 40 22952044
2010 Transcriptional corepressor TLE1 functions with Runx2 in epigenetic repression of ribosomal RNA genes. Proceedings of the National Academy of Sciences of the United States of America 40 20160071
2014 TLE1 promotes EMT in A549 lung cancer cells through suppression of E-cadherin. Biochemical and biophysical research communications 39 25446087
2010 TLE1 expression in malignant mesothelioma. Virchows Archiv : an international journal of pathology 39 20857142
2012 Immunohistochemical validation of TLE1, a novel marker, for synovial sarcomas. The Indian journal of medical research 36 23287123
2014 Structure of the type VI secretion phospholipase effector Tle1 provides insight into its hydrolysis and membrane targeting. Acta crystallographica. Section D, Biological crystallography 32 25084336
2006 Identification and targeted disruption of the mouse gene encoding ESG1 (PH34/ECAT2/DPPA5). BMC developmental biology 32 16504174
2008 Inhibition of cortical neuron differentiation by Groucho/TLE1 requires interaction with WRPW, but not Eh1, repressor peptides. The Journal of biological chemistry 31 18611861
1994 A cis-acting region required for the regulated expression of grg-1, a Neurospora glucose-repressible gene. Two regulatory sites (CRE and NRS) are required to repress grg-1 expression. Journal of molecular biology 31 8133521
2011 The role of TLE1 in synovial sarcoma. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 30 21319215
2011 TLE1 modifies the effects of NOD2 in the pathogenesis of Crohn's disease. Gastroenterology 30 21699783
2006 Esg1, expressed exclusively in preimplantation embryos, germline, and embryonic stem cells, is a putative RNA-binding protein with broad RNA targets. Development, growth & differentiation 30 16872451
2019 Endothelial surface glycocalyx (ESG) components and ultra-structure revealed by stochastic optical reconstruction microscopy (STORM). Biorheology 29 31045510
2003 Binding of the corepressor TLE1 to Qin enhances Qin-mediated transformation of chicken embryo fibroblasts. Oncogene 29 12660810
2013 Reappraisal of TLE-1 immunohistochemical staining and molecular detection of SS18-SSX fusion transcripts for synovial sarcoma. Pathology international 27 24422953
2003 Identification of PNRC2 and TLE1 as activation function-1 cofactors of the orphan nuclear receptor ERRgamma. Biochemical and biophysical research communications 27 14651967
2018 Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma-initiating cells. Molecular oncology 26 29316219
2012 Transducin-like enhancer of Split-1 (TLE1) combines with Forkhead box protein G1 (FoxG1) to promote neuronal survival. The Journal of biological chemistry 26 22354967
2010 Corepressors TLE1 and TLE3 interact with HESX1 and PROP1. Molecular endocrinology (Baltimore, Md.) 25 20181723
2018 Expression of TLE-1 and CD99 in Carcinoma: Pitfalls in Diagnosis of Synovial Sarcoma. Applied immunohistochemistry & molecular morphology : AIMM 24 27753659
2013 Specificity of TLE1 expression in unclassified high-grade sarcomas for the diagnosis of synovial sarcoma. Applied immunohistochemistry & molecular morphology : AIMM 24 23197007
2014 PFP/ESG: automated protein function prediction servers enhanced with Gene Ontology visualization tool. Bioinformatics (Oxford, England) 23 25273111
2011 TLE1 is expressed in the majority of primary pleuropulmonary synovial sarcomas. Virchows Archiv : an international journal of pathology 21 22071579
2014 Grg3/TLE3 and Grg1/TLE1 induce monohormonal pancreatic β-cells while repressing α-cell functions. Diabetes 20 24487024
2009 Cofactor-activated phosphorylation is required for inhibition of cortical neuron differentiation by Groucho/TLE1. PloS one 20 19956621
2012 Evaluation of function predictions by PFP, ESG,and PSI-BLAST for moonlighting proteins. BMC proceedings 19 23173871
2010 Dynamic expression of Groucho-related genes Grg1 and Grg3 in foregut endoderm and antagonism of differentiation. Developmental dynamics : an official publication of the American Association of Anatomists 19 20108349
2017 TLE1 inhibits anoikis and promotes tumorigenicity in human lung cancer cells through ZEB1-mediated E-cadherin repression. Oncotarget 18 29069783
2015 The Esg Gene Is Involved in Nicotine Sensitivity in Drosophila melanogaster. PloS one 18 26222315
1994 Cloning of embryonal stem cell-specific genes: characterization of the transcriptionally controlled gene esg-1. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 17 8123591
2016 The Anoikis Effector Bit1 Inhibits EMT through Attenuation of TLE1-Mediated Repression of E-Cadherin in Lung Cancer Cells. PloS one 15 27655370
2002 mgm 1, the earliest sex-specific germline marker in Drosophila, reflects expression of the gene esg in male stem cells. The International journal of developmental biology 15 11902678
2020 lncRNA RASSF8‑AS1 suppresses the progression of laryngeal squamous cell carcinoma via targeting the miR‑664b‑3p/TLE1 axis. Oncology reports 14 33000257
2024 Esculentoside H reduces the PANoptosis and protects the blood-brain barrier after cerebral ischemia/reperfusion through the TLE1/PI3K/AKT signaling pathway. Experimental neurology 13 38857750
2023 GRg1 inhibits the TLR4/NF-kB signaling pathway by upregulating miR-216a-5p to reduce growth factors and inflammatory cytokines in DR. Molecular biology reports 13 37819496
2023 Unusual Aspects of Small Cell Carcinoma of the Ovary of Hypercalcaemic Type: Retained SMARCA4 Immunohistochemical Staining and Positive Staining With TLE1. The American journal of surgical pathology 12 37345679
2023 Phenethyl isothiocyanate inhibits metastasis potential of non-small cell lung cancer cells through FTO mediated TLE1 m6A modification. Acta pharmacologica Sinica 12 37848553
2018 Expression of TLE1 in Malignant Melanoma With Spindle Cell Morphology: A Potential Diagnostic Pitfall. International journal of surgical pathology 11 30301396
2015 The PFP and ESG protein function prediction methods in 2014: effect of database updates and ensemble approaches. GigaScience 11 26380077
2010 Safety evaluation of an enzymatically-synthesized glycogen (ESG). Regulatory toxicology and pharmacology : RTP 11 20197075
2020 Tle1 attenuates hepatic ischemia/reperfusion injury by suppressing NOD2/NF-κB signaling. Bioscience, biotechnology, and biochemistry 10 32114961
2015 Trichostatin A suppresses lung adenocarcinoma development in Grg1 overexpressing transgenic mice. Biochemical and biophysical research communications 10 26086099
2024 Foxq1 Promotes Alveolar Epithelial Cell Death through Tle1-mediated Inhibition of the NF-κB Signaling Pathway. American journal of respiratory cell and molecular biology 9 38574238
2020 Reduced Expression of the Co-regulator TLE1 in Type 2 Diabetes Is Associated with Increased Islet α-Cell Number. Endocrinology 9 32065829
2021 Gene of the month: TLE 1. Journal of clinical pathology 8 33441390
2019 Frequent TLE1 Expression in Cutaneous Neoplasms. The American Journal of dermatopathology 8 30608261
2019 Is TLE1 Expression Limited to Synovial Sarcoma? Our Experience at Shifa International Hospital, Pakistan. Cureus 8 31893185
2017 Ras-Erk signaling induces phosphorylation of human TLE1 and downregulates its repressor function. Oncogene 8 28192406
2017 Structure-Enabled Discovery of a Stapled Peptide Inhibitor to Target the Oncogenic Transcriptional Repressor TLE1. Chemistry (Weinheim an der Bergstrasse, Germany) 8 28326635
2018 TLE1, a key player in neurogenesis, a new candidate gene for autosomal recessive postnatal microcephaly. European journal of medical genetics 7 29758293
2017 Using PFP and ESG Protein Function Prediction Web Servers. Methods in molecular biology (Clifton, N.J.) 7 28451967
2016 Transducer-like enhancer of split 1 (TLE1) expression as a diagnostic immunohistochemical marker for synovial sarcoma and its association with morphological features. The Malaysian journal of pathology 7 27568668
2024 Manufacturing enterprises move towards sustainable development: ESG performance, market-based environmental regulation, and green technological innovation. Journal of environmental management 6 39561457
2023 The utility of TLE1 and BCOR as immunohistochemical markers for angiomatoid fibrous histiocytoma. International journal of clinical and experimental pathology 6 36910892
2021 Diagnostic Utility of TLE1 (Transducer-Like Enhancer of Split 1) in Distinguishing Synovial Sarcoma from Mimicking Tumors. International journal of general medicine 6 34880656
2019 Transducer-like enhancer of split 1 (TLE1) as a novel biomarker for diagnosis of synovial sarcoma correlates with translocation t(X;18): a study of 155 cases in China. International journal of clinical and experimental pathology 6 31933740
2005 Dendritic localization of the transcriptional co-repressor Groucho/TLE1 in cortical and cerebellar neurons. Brain research. Molecular brain research 6 16081186
1998 Growth medium-dependent regulation of Myxococcus xanthus fatty acid content is controlled by the esg locus. Journal of bacteriology 6 9748468
2025 Unveiling Greenwashing: Analyzing the interaction of factors discouraging ESG Greenwashing through TISM and MICMAC. Journal of environmental management 5 40073478
2025 ESG-1-60 and ESG-1-61: Novel dopamine D3 receptor-preferring partial agonists/antagonists that inhibit cocaine taking and seeking in rodents. British journal of pharmacology 5 40150927
2002 The transcription co-repressor TLE1 interacted with the intracellular region of gpl30 through its Q domain. Molecular and cellular biochemistry 5 12030375
2013 In-depth performance evaluation of PFP and ESG sequence-based function prediction methods in CAFA 2011 experiment. BMC bioinformatics 4 23514353
2021 Differential functions of TLE1 and TLE3 depending on a specific phosphorylation site. Biochemical and biophysical research communications 3 33571907
2021 Tissue microarray based immunohistochemical study of TLE1 in synovial sarcoma and its histologic mimics. Indian journal of pathology & microbiology 3 33851625
2019 TLE-1-Positive Angiomatoid Fibrous Histiocytoma Mimicking Synovial Sarcoma. Applied immunohistochemistry & molecular morphology : AIMM 3 28248724
2013 A Case of Distal Epithelioid Sarcoma of the Thumb Expressing Podoplanin, TLE1 and Ca 125. Case reports in pathology 3 23691400
2024 ESG performance and green innovation of Chinese enterprises: Based on the perspective of financing constraints. Journal of environmental management 2 39423627
2023 Expression of TLE1 in a Carcinoid Tumor of the Lung With Spindle Cell Morphology-A Potential Diagnostic Pitfall. Applied immunohistochemistry & molecular morphology : AIMM 2 37668410
2021 Expression of TLE1, INI1, β-catenin, Claudin1, CK7, CK19, SS18 and calponin in synovial sarcoma. Indian journal of pathology & microbiology 2 34673590
2019 A rare case of TLE1-positive sclerosing epithelioid fibrosarcoma expanding the differential diagnosis of TLE1-positive tumors: a case report. AME case reports 2 31020273
2019 TLE1 expression fails to distinguish between synovial sarcoma, atypical fibroxanthoma, and dermatofibrosarcoma protuberans. Journal of cutaneous pathology 2 31614009
2018 TLE1 Positive Clear Cell Sarcoma of the Kidney: A Case Report and Review of the Literature. Case reports in pathology 2 30410809
2017 Epigenetic modification of TLE1 induce abnormal differentiation in diabetic mice intestinal epithelium. Molecular and cellular biochemistry 2 28744818
2016 Generation of a TLE1 homozygous knockout human embryonic stem cell line using CRISPR-Cas9. Stem cell research 2 27879218
2024 TLE1 corepressor promotes gefitinib resistance in lung cancer A549 cells via E‑cadherin silencing. Biomedical reports 1 39781042
2023 Expression of TLE-1 in Gastrointestinal Stromal Tumour and Its Relationship to Clinicopathological Parameters. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP 1 36945158
2018 TLE1 Expression in Malignant Rhabdoid Tumor and Atypical Teratoid/Rhabdoid Tumor. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 1 29490565
2026 "Molecular insights into the bactericidal toxin Tle1 of Pseudomonas aeruginosa: Interaction with VgrG, its adaptor, and its immunity protein". The Journal of biological chemistry 0 41933729
2025 Differential Expression of TLE1 in Small Round Cell Tumors: A Proposed Solution for Challenging Differentials Impacting Treatment Strategies. International journal of surgical pathology 0 40335446
2025 CN-VEFD: A visual emotion feature dataset for Chinese ESG reports. Data in brief 0 41403958
2010 Expression, purification, crystallization, and preliminary X-ray diffraction analysis of the human TLE1 Q domain. Acta biochimica et biophysica Sinica 0 21183761