Affinage

TBL1XR1

F-box-like/WD repeat-containing protein TBL1XR1 · UniProt Q9BZK7

Length
514 aa
Mass
55.6 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TBL1XR1 (TBLR1) is a core WD40-repeat subunit of the NCoR/SMRT transcriptional corepressor complex that converts ligand- and signal-dependent cues into transcriptional switching at chromatin (PMID:12628926, PMID:18374649). It engages N-CoR through two independent contacts—an N-terminal interaction with the N-CoR RD1 region and a C-terminal WD40 interaction with RD4—and binds histones H2B and H4, with repression tracking its histone interaction (PMID:12628926). Beyond serving as a structural scaffold, it functions as a signal-responsive exchange factor that licenses ubiquitin-dependent degradation of corepressors—dismissing NCoR/SMRT (while its paralog TBL1 acts on CtBP1/2)—to enable transcriptional activation across nuclear-receptor, Notch, and NF-κB pathways; this specificity is encoded by Ser/Thr phosphorylation sites, with PKCδ phosphorylating TBLR1 at the promoter to drive NCoR dismissal (PMID:18374649). Wnt signaling redirects TBL1XR1 into a β-catenin complex required for Wnt target-gene transcription and oncogenic growth, a switch gated by SUMOylation that dissociates TBL1XR1 from NCoR and is reversed by SENP-family de-SUMOylation (PMID:18193033, PMID:21777810). The protein's exchange-factor activity also operates on specific transcription factors: it is recruited by unliganded thyroid hormone receptor and by the PML-RARα/PLZF-RARα oncoproteins to enforce repression that is relieved by ligand (PMID:15060155, PMID:12794076), and it sustains glucocorticoid- and androgen-receptor signaling by controlling NCoR1/HDAC3 levels at responsive loci (PMID:24895125, PMID:24243687). In B-cell biology, TBL1XR1 directs SMRT/HDAC3 to lineage transcription factors, and lymphoma-associated WD40 mutations co-opt these complexes from BCL6 toward BACH2 to drive pre-memory reprogramming and impaired plasma-cell differentiation (PMID:32619424). A co-crystal structure defines its direct WD40-mediated binding to the MeCP2 NID, and intellectual-disability mutations in TBL1XR1 abolish this contact (PMID:28348241). Germline TBL1XR1 mutations cause neurodevelopmental disease: a p.Tyr446Cys allele that assembles normally into NCoR/SMRT causes Pierpont syndrome via a dominant-negative mechanism, distinct from loss-of-function alleles associated with autism (PMID:26769062).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2003 High

    Established TBL1XR1 as a histone-contacting NCoR-binding subunit, defining how it is physically wired into the corepressor machinery and why it is required for nuclear-receptor repression.

    Evidence Protein purification, Co-IP, in vitro histone-binding assays, and siRNA knockdown with reporter readout

    PMID:12628926

    Open questions at the time
    • Histone binding shown in vitro; chromatin-level contribution at native loci not resolved
    • Redundancy with TBL1 leaves individual contribution ambiguous
  2. 2003 High

    Showed oncogenic fusion receptors exploit the TBLR1/N-CoR axis, linking the corepressor subunit to leukemic transcriptional silencing.

    Evidence Frog oocyte chromatin system, Co-IP, ChIP, and dominant-negative N-CoR expression with PML-RARα/PLZF-RARα

    PMID:12794076

    Open questions at the time
    • Demonstrated in oocyte chromatin, not human leukemic cells
    • Did not address derepression dynamics in patients
  3. 2004 High

    Demonstrated ligand-dependent release of TBLR1/SMRT/N-CoR at thyroid-receptor promoters in vivo, establishing the corepressor-to-activator switch on physiological targets.

    Evidence ChIP and in vivo interaction assays in frog oocytes and during amphibian metamorphosis with dominant-negative N-CoR

    PMID:15060155

    Open questions at the time
    • Mechanism of release not biochemically dissected here
    • Amphibian system; mammalian generality assumed
  4. 2008 High

    Identified TBL1XR1 as a signal-responsive exchange factor that licenses ubiquitin-mediated corepressor degradation, providing the core mechanistic model for how it enables activation, with phosphorylation encoding specificity.

    Evidence Phosphorylation-site mutagenesis, kinase assays, ubiquitylation assays, and ChIP across Notch/NF-κB/nuclear-receptor contexts

    PMID:18374649

    Open questions at the time
    • Identity of the recruited ubiquitin ligase not fully defined
    • How phosphorylation discriminates CtBP vs NCoR targets at structural level unresolved
  5. 2008 High

    Placed TBL1XR1 in Wnt/β-catenin transcription, showing signal-induced β-catenin association and a requirement for Wnt-driven gene expression and oncogenic growth.

    Evidence Co-IP, ChIP, siRNA knockdown, and in vitro/in vivo oncogenic growth assays

    PMID:18193033

    Open questions at the time
    • Did not yet explain how the NCoR-to-β-catenin switch is triggered
    • Direct vs indirect β-catenin contact unresolved
  6. 2011 High

    Defined SUMOylation as the molecular switch that releases TBL1XR1 from NCoR and recruits it to β-catenin, mechanistically connecting the 2008 Wnt and exchange-factor findings.

    Evidence SUMOylation assays, Co-IP, ChIP, SENP1 manipulation, and tumorigenicity assays in colon cancer cells

    PMID:21777810

    Open questions at the time
    • SUMO E3 ligase not identified
    • Stoichiometry of SUMOylated vs unmodified pools unknown
  7. 2014 High

    Extended the corepressor-control role to therapy response, showing TBL1XR1 governs glucocorticoid-receptor recruitment by limiting NCoR1/HDAC3 and that loss drives glucocorticoid resistance reversible by HDAC inhibition.

    Evidence shRNA knockdown, GR ChIP, drug-sensitivity assays, and SAHA rescue in B-precursor ALL cells

    PMID:24895125

    Open questions at the time
    • Whether resistance generalizes beyond B-ALL not tested
    • Did not define how TBL1XR1 sets steady-state NCoR1/HDAC3 levels
  8. 2014 High

    Showed TBL1XR1 can act as an androgen-receptor coactivator selecting differentiation over proliferation genes, demonstrating context-specific, gene-selective output.

    Evidence Co-IP, ChIP, stable overexpression, and in vitro/in vivo growth assays in prostate cancer

    PMID:24243687

    Open questions at the time
    • Basis for selective activation of KRT18/NKX3-1 versus proliferative genes unresolved
    • Role of 19S proteasome dependence mechanistically undefined
  9. 2010 Medium

    Reported a direct E3-ligase-like activity for TBLR1 toward BCL-3, expanding its repertoire from exchange factor to a degradation effector.

    Evidence Biochemical purification, Co-IP, and ubiquitination/degradation assays

    PMID:20547759

    Open questions at the time
    • Whether TBLR1 is a bona fide catalytic ligase or adaptor not fully distinguished
    • Single-lab finding without structural basis
  10. 2016 Medium

    Generalized the SUMO switch to inflammatory signaling, showing TNF-α-induced SUMOylation builds a TBL1-TBLR1-NF-κB activating complex reversed by SENP1.

    Evidence SUMOylation assays, Co-IP, gene-expression analysis, and knockdown in prostate cancer cells

    PMID:27129164

    Open questions at the time
    • Functional readouts emphasized TBL1 over TBLR1
    • Direct TBLR1-NF-κB contact not structurally defined
  11. 2015 Medium

    Confirmed SUMO-dependent β-catenin nuclear translocation via TBL1/TBLR1 in a second cancer context and identified SENP2 as a reversing enzyme.

    Evidence Co-IP, nuclear fractionation, SENP2 manipulation, and luciferase reporter in bladder cancer cells

    PMID:26369384

    Open questions at the time
    • Single-lineage findings
    • Mechanism of SUMO-driven nuclear shuttling not resolved
  12. 2017 High

    Provided atomic-resolution definition of TBL1XR1 WD40 binding to the MeCP2 NID and linked disease mutations on both proteins to disrupted contact.

    Evidence Co-crystal structure with in vitro and ex vivo mutagenesis binding assays

    PMID:28348241

    Open questions at the time
    • Functional consequence of MeCP2 binding for specific gene programs not addressed
    • Did not test neuronal phenotypes of binding loss
  13. 2017 Medium

    Showed lymphoma WD40 mutations are gain-of-function for NCoR binding, increasing NCoR degradation and activating NF-κB/JUN targets, linking somatic mutation to aberrant activation.

    Evidence Co-IP and gene-expression analysis with mutant constructs in 293T cells

    PMID:28152507

    Open questions at the time
    • Tested in 293T overexpression, not patient lymphoma cells
    • Genome-wide consequences not assessed
  14. 2017 Medium

    Demonstrated TBL1XR1 can act directly at a target promoter (VEGF-C) to drive lymphangiogenesis and metastasis, evidencing transcription-factor-like promoter occupancy.

    Evidence ChIP, luciferase reporter, knockdown, and in vivo metastasis model in esophageal carcinoma

    PMID:24667177

    Open questions at the time
    • Direct DNA binding vs tethered recruitment not distinguished
    • Single tumor type
  15. 2016 Medium

    Distinguished disease mechanisms by showing the Pierpont-syndrome p.Tyr446Cys allele incorporates normally into NCoR/SMRT, implicating dominant-negative action rather than failed assembly.

    Evidence Protein expression and complex-assembly Co-IP from HEK293 cells

    PMID:26769062

    Open questions at the time
    • Dominant-negative mechanism inferred, not directly demonstrated functionally
    • Single assembly assay
  16. 2017 Medium

    Showed a de novo neurodevelopmental allele (Phe10Leu) alters both N-CoR and β-catenin interactions and elevates Wnt signaling, connecting the N-terminal interaction surface to disease.

    Evidence Co-IP and Wnt reporter assays with mutant protein

    PMID:28588275

    Open questions at the time
    • Cell-based reporter only
    • In vivo neurodevelopmental relevance not tested
  17. 2020 High

    Defined how lymphoma mutations rewire B-cell fate by redistributing SMRT/HDAC3 from BCL6 to BACH2, causing pre-memory reprogramming and lymphomagenesis in vivo.

    Evidence Mouse knock-in model, ChIP-seq, gene-expression profiling, and B-cell differentiation/lymphoma phenotyping

    PMID:32619424

    Open questions at the time
    • Why mutant complexes prefer BACH2 over BCL6 mechanistically unresolved
    • Generalizability across lymphoma subtypes not established
  18. 2020 Medium

    Identified USP1 as a deubiquitinase that stabilizes TBL1XR1 protein, revealing post-translational control of its abundance that feeds Wnt-driven tumor-cell survival.

    Evidence Co-IP, ubiquitination assay, USP1 knockout, and protein-stability Western blots in hepatocellular carcinoma

    PMID:33102219

    Open questions at the time
    • Ubiquitin ligase opposing USP1 not identified
    • Single-lineage functional context
  19. 2021 Medium

    Connected TBL1XR1/NCoR complex function to neurodevelopmental phenotypes mechanistically through MAPK-cascade regulation governing neural progenitor proliferation and differentiation.

    Evidence Tbl1xr1 knockout mouse with neural progenitor assays, MAPK pathway analysis, and behavioral testing

    PMID:33708771

    Open questions at the time
    • How NCoR complex couples to MAPK output not biochemically defined
    • Behavioral-to-molecular causal chain incomplete
  20. 2022 High

    Placed TBL1XR1 as a direct miR-130a target whose loss expands HSCs and impairs B-lymphoid differentiation, implicating it in AML1-ETO leukemic programs.

    Evidence AGO2 CLIP-seq, mass spectrometry, and loss-of-function in primary human HSCs with miR-130a overexpression

    PMID:35263585

    Open questions at the time
    • Downstream NCoR-complex targets in HSCs not mapped
    • Mechanism linking TBL1XR1 to AML1-ETO program undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural rules that determine whether TBL1XR1 dismisses versus stabilizes corepressors—and how phosphorylation, SUMOylation, and mutations bias this choice between repression and activation at specific loci—remain incompletely defined.
  • The ubiquitin ligase(s) recruited during corepressor dismissal are unidentified
  • No unified structural model linking phospho/SUMO state to exchange-factor versus stabilizer behavior
  • Whether TBLR1 itself is catalytically a ligase or an adaptor remains unsettled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0016874 ligase activity 1 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-4839726 Chromatin organization 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 3
Partners
ARBCL3CTNNB1HDAC3MECP2NCOR1NCOR2NR3C1
Complex memberships
NCoR/SMRT corepressor complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 TBLR1 associates with N-CoR through two independent interactions: the N-terminal region of TBL1/TBLR1 interacts with the N-CoR RD1 region, and the C-terminal WD-40 repeats interact with the N-CoR RD4 region. In vitro, TBLR1 binds histones H2B and H4, and repression by TBLR1 correlates with histone interaction. siRNA knockdown demonstrated TBLR1 is functionally redundant with TBL1 but essential for repression by unliganded thyroid hormone receptor. Protein purification, Co-IP, in vitro histone-binding assays, siRNA knockdown with reporter gene readout The EMBO journal High 12628926
2008 TBL1 and TBLR1 are required for Wnt/β-catenin-mediated transcription. Wnt signaling induces interaction between β-catenin and TBL1-TBLR1. Recruitment of TBL1-TBLR1 and β-catenin to Wnt target-gene promoters is mutually dependent. Depletion of TBL1-TBLR1 significantly inhibited Wnt-β-catenin-induced gene expression and oncogenic growth in vitro and in vivo. Co-IP, chromatin immunoprecipitation (ChIP), siRNA knockdown, in vitro and in vivo oncogenic growth assays Nature cell biology High 18193033
2008 TBL1 and TBLR1 function as exchange factors that license ubiquitylation and proteasomal degradation of CtBP1/2 and NCoR/SMRT corepressors, respectively, enabling transcriptional activation across multiple signaling pathways (Notch, NF-κB, nuclear receptor ligands). Their differential specificity resides in five specific Ser/Thr phosphorylation site differences; PKCδ directly phosphorylates TBLR1 at the promoter to enable NCoR dismissal. Phosphorylation site mutagenesis, kinase assays, ubiquitylation assays, ChIP, siRNA knockdown with gene-expression readouts Molecular cell High 18374649
2004 TBLR1 is recruited by unliganded thyroid hormone receptor (TR) to chromatinized target promoters in vivo, accompanied by histone deacetylation and gene repression. TBLR1, SMRT, and N-CoR are released from TR target promoters upon T3 treatment, which correlates with gene activation during amphibian metamorphosis. Frog oocyte system, chromatin immunoprecipitation (ChIP), in vivo interaction assays, dominant-negative N-CoR expression Molecular and cellular biology High 15060155
2003 PML-RARα and PLZF-RARα oncoproteins recruit TBLR1 and N-CoR to their target promoters in chromatin, leading to histone deacetylation and transcriptional repression. Expression of a dominant-negative N-CoR containing the TBLR1-interacting domain blocked transcription repression by unliganded PML-RARα and PLZF-RARα. Frog oocyte chromatin system, Co-IP, chromatin immunoprecipitation (ChIP), dominant-negative expression The Journal of biological chemistry High 12794076
2011 Both TBL1 and TBLR1 are SUMOylated in a Wnt signaling-dependent manner. SUMOylation dismisses TBL1-TBLR1 from the NCoR complex, increases formation of the TBL1-TBLR1-β-catenin complex at Wnt target gene promoters, and activates Wnt signaling. SENP1-mediated de-SUMOylation reverses this, inhibiting β-catenin-mediated transcription. Inhibition of SUMOylation decreased tumorigenicity of SW480 colon cancer cells. SUMOylation assays, Co-IP, ChIP, SENP1 overexpression/knockdown, cell-based tumorigenicity assays Molecular cell High 21777810
2017 The crystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 was determined. MeCP2 directly contacts TBLR1 (and TBL1) as core components of the NCoR/SMRT complex. The four MeCP2-NID residues mutated in Rett syndrome make the most extensive contacts with TBLR1. Missense mutations in TBL1XR1 associated with intellectual disability also prevent MeCP2 binding, confirmed by in vitro and ex vivo binding assays. Co-crystal structure determination, in vitro binding assays, ex vivo interaction assays, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 28348241
2006 TBLR1 co-precipitates with SMRT and co-precipitates in complexes immunoprecipitated by anti-HDAC3 antiserum. In resting cells TBLR1 is primarily cytoplasmic, but after perturbation it translocates to the nucleus. Overexpression of TBLR1 or its deletion variants elevates endogenous N-CoR and SMRT levels, suggesting TBLR1 stabilizes corepressors against ubiquitin-mediated degradation. Transient overexpression of TBLR1 produces growth arrest. Co-immunoprecipitation, immunofluorescence localization, Western blot, overexpression of deletion variants BMC cell biology Medium 16893456
2014 TBL1XR1 knockdown in B-precursor ALL cell lines reduces glucocorticoid receptor (GR) recruitment to glucocorticoid-responsive gene chromatin and decreases glucocorticoid signaling, caused by increased levels of nuclear hormone repressor 1 (NCoR1) and HDAC3. This results in resistance to glucocorticoid agonists but not to other chemotherapeutic agents. HDAC inhibitor SAHA treatment restores prednisolone sensitivity in TBL1XR1-depleted cells. siRNA/shRNA knockdown, ChIP for GR recruitment, gene expression analysis, drug sensitivity assays, HDAC inhibitor rescue The Journal of biological chemistry High 24895125
2014 TBLR1 physically interacts with androgen receptor (AR) and occupies androgen-response elements of AR target genes in an androgen-dependent manner, functioning as an AR coactivator. Coactivator activity is dependent on phosphorylation and the 19S proteasome. Stable nuclear TBLR1 expression causes androgen-dependent growth suppression of prostate cancer cells in vitro and in vivo by selectively activating differentiation- and growth-suppression-associated AR target genes (KRT18, NKX3-1) but not proliferative genes. Co-IP, ChIP, stable overexpression, in vitro and in vivo growth assays, gene expression profiling Endocrine-related cancer High 24243687
2014 The TBLR1-RARα fusion protein found in APL forms homodimers and heterodimers with RXRα and exhibits diminished transcriptional activity by recruiting more transcriptional corepressors compared with wild-type RARα. In the presence of pharmacological doses of ATRA, TBLR1-RARα is degraded, homodimerization is abrogated, and the fusion mediates dissociation and degradation of transcriptional corepressors, inducing transactivation of RARα target genes and cell differentiation. Co-IP (dimerization assays), reporter gene assays, Western blot (degradation), cell differentiation assays Blood Medium 24782508
2010 TBLR1 functions as an E3 ubiquitin ligase responsible for BCL-3 polyubiquitination and degradation through a GSK3-independent pathway. Biochemical purification identified TBLR1 as a BCL-3-interacting protein involved in its proteasomal degradation. Biochemical purification, Co-IP, ubiquitination assays, degradation assays Molecular and cellular biology Medium 20547759
2016 TBL1 and TBLR1 are SUMOylated in response to TNF-α treatment, increasing formation of a TBL1-TBLR1-NF-κB complex that leads to NF-κB-mediated transcriptional activation of cytokine genes. SENP1-mediated de-SUMOylation of TBL1 and TBLR1 dissociates them from the NCoR complex and inhibits NF-κB target gene expression. TBL1 knockdown suppresses inflammatory signaling and PC-3 prostate cancer cell proliferation. SUMOylation assays, Co-IP, gene expression analysis, siRNA knockdown, cell proliferation assays Oncotarget Medium 27129164
2015 SENP2-mediated de-SUMOylation of TBL1/TBLR1 inhibits nuclear translocation of β-catenin and suppresses MMP13 expression in bladder cancer cells. WNT ligands induce TBL1/TBLR1 SUMOylation to form complexes with β-catenin, facilitating β-catenin nuclear translocation, which can be blocked by inhibiting TBL1/TBLR1 SUMOylation. Co-IP, nuclear fractionation, Western blot, SENP2 knockdown/overexpression, luciferase reporter assay Scientific reports Medium 26369384
2017 TBL1XR1 mutations found in ocular marginal zone lymphoma (within the WD40 domain) increase TBL1XR1 binding to NCoR, leading to increased NCoR degradation and activation of NF-κB and JUN target genes in 293T cells. Co-IP (TBL1XR1-NCoR interaction), transfection of mutant constructs into 293T cells, gene expression analysis Oncotarget Medium 28152507
2020 TBL1XR1 mutations co-opt SMRT/HDAC3 repressor complexes toward binding the memory B cell transcription factor BACH2 at the expense of the germinal center TF BCL6, leading to pre-memory transcriptional reprogramming, impaired plasma cell differentiation, and extranodal immunoblastic lymphoma in mice. TBL1XR1 mutant memory B cells fail to differentiate into plasma cells upon antigen recall and preferentially re-enter germinal center reactions. Mouse genetic model (knock-in mutations), ChIP-seq for SMRT/HDAC3 binding, gene expression profiling, B cell differentiation assays in vitro and in vivo, lymphoma phenotyping Cell High 32619424
2017 TBL1XR1 induces VEGF-C expression by directly binding to the VEGF-C promoter, thereby promoting lymphangiogenesis and lymphatic metastasis in esophageal squamous cell carcinoma. This was demonstrated by ChIP showing TBL1XR1 occupancy at the VEGF-C promoter, and luciferase reporter assays. ChIP, luciferase reporter assay, siRNA knockdown, in vitro invasion/tube formation assays, in vivo lymph node metastasis model Gut Medium 24667177
2016 The TBL1XR1 p.Tyr446Cys mutation causing Pierpont syndrome assembles correctly into the NCoR/SMRT complex, suggesting a dominant-negative mechanism rather than loss of complex assembly. This contrasts with loss-of-function mutations/deletions causing autism without the Pierpont phenotype. Protein expression and purification from HEK293 cells, complex assembly assay (co-immunoprecipitation with NCoR/SMRT components) Journal of medical genetics Medium 26769062
2017 A de novo TBL1XR1 Phe10Leu mutation alters the interaction of TBL1XR1 with both N-CoR and β-catenin, and up-regulates TBL1XR1-mediated activation of Wnt signaling in cell-based assays. Co-IP (TBL1XR1 with N-CoR and β-catenin), Wnt reporter assays, protein structural analysis Scientific reports Medium 28588275
2020 USP1 deubiquitinates and stabilizes TBLR1 (TBL1XR1), protecting it from proteasomal degradation. USP1-mediated stabilization of TBLR1 promotes Wnt signaling and the survival of hepatocellular carcinoma circulating tumor cells. Co-IP, ubiquitination assay, USP1 knockout, Western blot for TBLR1 protein stability Frontiers in oncology Medium 33102219
2017 SLY interacts with TBL1XR1 in postmeiotic male germ cells, as demonstrated by co-immunoprecipitation. This interaction places TBL1XR1/SMRT-NCoR repressor complex members as regulators of gene expression during sperm differentiation. Co-immunoprecipitation from postmeiotic germ cells Cell death and differentiation Low 28475176
2021 Tbl1xr1 knockout mice exhibit behavioral and neuronal abnormalities. Either absence of TBL1XR1 or point mutations interfering with NCOR complex stability/regulation causes decreased proliferation and increased differentiation in neural progenitors, attributed to failure in regulation of the MAPK cascade. Tbl1xr1 knockout mouse model, neural progenitor cell proliferation/differentiation assays, MAPK pathway analysis, behavioral testing Frontiers in cell and developmental biology Medium 33708771
2022 TBL1XR1 is a primary direct target of miR-130a identified by AGO2 CLIP. Loss of TBL1XR1 function phenocopies miR-130a overexpression, impairing B lymphoid differentiation and expanding long-term hematopoietic stem cells (HSCs). TBL1XR1 is critical for the oncogenic molecular program mediated by AML1-ETO in t(8;21) AML. AGO2 CLIP-seq, protein mass spectrometry, TBL1XR1 loss-of-function in primary human HSCs, miR-130a overexpression, gene expression profiling Cell reports High 35263585

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1. The EMBO journal 374 12628926
1990 S. cerevisiae genes IRA1 and IRA2 encode proteins that may be functionally equivalent to mammalian ras GTPase activating protein. Cell 301 2178777
1981 Microsomal cytochrome P-450 from neonatal pig testis. Purification and properties of A C21 steroid side-chain cleavage system (17 alpha-hydroxylase-C17,20 lyase). The Journal of biological chemistry 282 6971291
1988 Aberrant splicing and missense mutations cause steroid 21-hydroxylase [P-450(C21)] deficiency in humans: possible gene conversion products. Proceedings of the National Academy of Sciences of the United States of America 238 2845408
1989 IRA1, an inhibitory regulator of the RAS-cyclic AMP pathway in Saccharomyces cerevisiae. Molecular and cellular biology 226 2540426
1990 Human 3 beta-hydroxysteroid dehydrogenase/delta 5----4isomerase from placenta: expression in nonsteroidogenic cells of a protein that catalyzes the dehydrogenation/isomerization of C21 and C19 steroids. Endocrinology 223 2139411
1990 Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway. Nature 202 2169593
1984 C21 steroid side chain cleavage enzyme from porcine adrenal microsomes. Purification and characterization of the 17 alpha-hydroxylase/C17,20-lyase cytochrome P-450. The Journal of biological chemistry 200 6608525
2012 Recurrent mutations of MYD88 and TBL1XR1 in primary central nervous system lymphomas. Clinical cancer research : an official journal of the American Association for Cancer Research 197 22837180
1988 Evidence for frequent gene conversion in the steroid 21-hydroxylase P-450(C21) gene: implications for steroid 21-hydroxylase deficiency. American journal of human genetics 172 2827462
2008 TBL1-TBLR1 and beta-catenin recruit each other to Wnt target-gene promoter for transcription activation and oncogenesis. Nature cell biology 171 18193033
1991 Effects of individual mutations in the P-450(C21) pseudogene on the P-450(C21) activity and their distribution in the patient genomes of congenital steroid 21-hydroxylase deficiency. Journal of biochemistry 168 1869518
2008 TBL1 and TBLR1 phosphorylation on regulated gene promoters overcomes dual CtBP and NCoR/SMRT transcriptional repression checkpoints. Molecular cell 136 18374649
2004 Recruitment of N-CoR/SMRT-TBLR1 corepressor complex by unliganded thyroid hormone receptor for gene repression during frog development. Molecular and cellular biology 103 15060155
2011 Reversible SUMOylation of TBL1-TBLR1 regulates β-catenin-mediated Wnt signaling. Molecular cell 97 21777810
2014 TBL1XR1 promotes lymphangiogenesis and lymphatic metastasis in esophageal squamous cell carcinoma. Gut 95 24667177
2020 TBL1XR1 Mutations Drive Extranodal Lymphoma by Inducing a Pro-tumorigenic Memory Fate. Cell 94 32619424
1994 Isolation of a CDC25 family gene, MSI2/LTE1, as a multicopy suppressor of ira1. Yeast (Chichester, England) 88 7941731
2003 5alpha-reduced C21 steroids are substrates for human cytochrome P450c17. Archives of biochemistry and biophysics 76 14522586
1997 The regio- and stereo-selectivity of C19 and C21 hydroxysteroid glucuronidation by UGT2B7 and UGT2B11. Archives of biochemistry and biophysics 66 9169006
2017 Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders. Proceedings of the National Academy of Sciences of the United States of America 63 28348241
2006 The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2. Molecular cell 58 16793550
1990 C19 and C21 5 beta/5 alpha metabolite ratios in subjects treated with the 5 alpha-reductase inhibitor finasteride: comparison of male pseudohermaphrodites with inherited 5 alpha-reductase deficiency. The Journal of clinical endocrinology and metabolism 57 1689740
2016 A specific mutation in TBL1XR1 causes Pierpont syndrome. Journal of medical genetics 56 26769062
1968 The biosynthesis of some androst-16-enes from C21 and C19 steroids in boar testicular and adrenal tissue. The Biochemical journal 55 4233122
2017 Correlations between TBL1XR1 and recurrence of colorectal cancer. Scientific reports 54 28295012
2012 TBL1XR1/TP63: a novel recurrent gene fusion in B-cell non-Hodgkin lymphoma. Blood 53 22496164
2017 The mutational landscape of ocular marginal zone lymphoma identifies frequent alterations in TNFAIP3 followed by mutations in TBL1XR1 and CREBBP. Oncotarget 52 28152507
2015 TBL1XR1 in physiological and pathological states. American journal of clinical and experimental urology 52 26069883
2014 Loss of TBL1XR1 disrupts glucocorticoid receptor recruitment to chromatin and results in glucocorticoid resistance in a B-lymphoblastic leukemia model. The Journal of biological chemistry 51 24895125
2014 TBLR1 fuses to retinoid acid receptor α in a variant t(3;17)(q26;q21) translocation of acute promyelocytic leukemia. Blood 50 24782508
2014 A girl with West syndrome and autistic features harboring a de novo TBL1XR1 mutation. Journal of human genetics 46 25102098
2008 The complex genomic profile of ETV6-RUNX1 positive acute lymphoblastic leukemia highlights a recurrent deletion of TBL1XR1. Genes, chromosomes & cancer 46 18767146
2004 Global co-ordination of protein translocation by the SecA IRA1 switch. The Journal of biological chemistry 44 15007058
1971 Resistance of Escherichia coli to penicillins. IX. Genetics and physiology of class II ampicillin-resistant mutants that are galactose negative or sensitive to bacteriophage C21, or both. Journal of bacteriology 43 4945191
2012 AT2 receptor non-peptide agonist C21 promotes natriuresis in obese Zucker rats. Hypertension research : official journal of the Japanese Society of Hypertension 42 22297475
2011 Synthesis and 5α-reductase inhibitory activity of C₂₁ steroids having 1,4-diene or 4,6-diene 20-ones and 4-azasteroid 20-oximes. Molecules (Basel, Switzerland) 42 22210173
2003 Fusion protein of retinoic acid receptor alpha with promyelocytic leukemia protein or promyelocytic leukemia zinc finger protein recruits N-CoR-TBLR1 corepressor complex to repress transcription in vivo. The Journal of biological chemistry 42 12794076
1997 Correlation between binding affinities of C21 steroids for the maturation-inducing steroid membrane receptor in spotted seatrout ovaries and their agonist and antagonist activities in an oocyte maturation bioassay. Biology of reproduction 41 9369163
2006 TBLR1 regulates the expression of nuclear hormone receptor co-repressors. BMC cell biology 40 16893456
2016 Angiotensin II Type 2-Receptor Agonist C21 Reduces Proteinuria and Oxidative Stress in Kidney of High-Salt-Fed Obese Zucker Rats. Hypertension (Dallas, Tex. : 1979) 39 27021008
2006 The glucuronidation of Delta4-3-Keto C19- and C21-hydroxysteroids by human liver microsomal and recombinant UDP-glucuronosyltransferases (UGTs): 6alpha- and 21-hydroxyprogesterone are selective substrates for UGT2B7. Drug metabolism and disposition: the biological fate of chemicals 39 17151189
1991 Interactions between adenylate cyclase and the yeast GTPase-activating protein IRA1. Molecular and cellular biology 39 1875942
2017 SLY regulates genes involved in chromatin remodeling and interacts with TBL1XR1 during sperm differentiation. Cell death and differentiation 38 28475176
2017 MicroRNA-130a-3p suppresses cell migration and invasion by inhibition of TBL1XR1-mediated EMT in human gastric carcinoma. Molecular carcinogenesis 38 29091326
2017 Adrenal C11-oxy C21 steroids contribute to the C11-oxy C19 steroid pool via the backdoor pathway in the biosynthesis and metabolism of 21-deoxycortisol and 21-deoxycortisone. The Journal of steroid biochemistry and molecular biology 37 28774496
2014 A new syndrome of intellectual disability with dysmorphism due to TBL1XR1 deletion. American journal of medical genetics. Part A 37 25425123
2021 Seven days treatment with the angiotensin II type 2 receptor agonist C21 in hospitalized COVID-19 patients; a placebo-controlled randomised multi-centre double-blind phase 2 trial. EClinicalMedicine 35 34723163
2015 SENP2 regulates MMP13 expression in a bladder cancer cell line through SUMOylation of TBL1/TBLR1. Scientific reports 34 26369384
2014 TBLR1 as an androgen receptor (AR) coactivator selectively activates AR target genes to inhibit prostate cancer growth. Endocrine-related cancer 34 24243687
2010 The repressing function of the oncoprotein BCL-3 requires CtBP, while its polyubiquitination and degradation involve the E3 ligase TBLR1. Molecular and cellular biology 33 20547759
2005 Phytoestrogen resveratrol suppresses steroidogenesis by rat adrenocortical cells by inhibiting cytochrome P450 c21-hydroxylase. Hormone research 33 16269870
1979 Characterization of a C21 neutral steroid hormone transforming enzyme, 21-dehydroxylase, in crude cell extracts of Eubacterium lentum. Biochimica et biophysica acta 32 38850
2012 Impact of the AT(2) receptor agonist C21 on blood pressure and beyond. Current hypertension reports 31 22836386
2017 TBL1XR1 predicts isolated tumor cells and micrometastasis in patients with TNM stage I/II colorectal cancer. Journal of gastroenterology and hepatology 30 28127799
2018 Angiotensin receptor (AT2R) agonist C21 prevents cognitive decline after permanent stroke in aged animals-A randomized double- blind pre-clinical study. Behavioural brain research 29 30296528
2020 HSP90AA1, ADRB2, TBL1XR1 and HSPB1 are chronic obstructive pulmonary disease-related genes that facilitate squamous cell lung cancer progression. Oncology letters 27 32194709
2019 BW18, a C-21 steroidal glycoside, exerts an excellent anti-leukemia activity through inducing S phase cell cycle arrest and apoptosis via MAPK pathway in K562 cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 30784914
2020 USP1 Maintains the Survival of Liver Circulating Tumor Cells by Deubiquitinating and Stabilizing TBLR1. Frontiers in oncology 25 33102219
2019 The 11β-hydroxyandrostenedione pathway and C11-oxy C21 backdoor pathway are active in benign prostatic hyperplasia yielding 11keto-testosterone and 11keto-progesterone. The Journal of steroid biochemistry and molecular biology 25 31626910
2018 Role of Long Noncoding RNA 799 in the Metastasis of Cervical Cancer through Upregulation of TBL1XR1 Expression. Molecular therapy. Nucleic acids 24 30439646
2011 Cytotoxic C21 and C22 terpenoid-derived metabolites from the sponge Ircinia sp. Journal of natural products 24 21902186
2020 Long Noncoding RNA Plasmacytoma Variant Translocation 1 Regulates Cisplatin Resistance via miR-3619-5p/TBL1XR1 Axis in Gastric Cancer. Cancer biotherapy & radiopharmaceuticals 23 32407172
2020 Lymphatic metastasis-related TBL1XR1 enhances stemness and metastasis in gastric cancer stem-like cells by activating ERK1/2-SOX2 signaling. Oncogene 23 33288885
2018 A high-throughput UPC2-MS/MS method for the separation and quantification of C19 and C21 steroids and their C11-oxy steroid metabolites in the classical, alternative, backdoor and 11OHA4 steroid pathways. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 23 29482121
2018 Chronic administration of the angiotensin type 2 receptor agonist C21 improves insulin sensitivity in C57BL/6 mice. Physiological reports 23 30156060
2018 C21 steroidal glycosides with cytotoxic activities from Cynanchum otophyllum. Bioorganic & medicinal chemistry letters 22 29625825
2019 TBL1XR1 is involved in c-Met-mediated tumorigenesis of human nonsmall cell lung cancer. Cancer gene therapy 21 31243347
2017 C21 steroid-enriched fraction refined from Marsdenia tenacissima inhibits hepatocellular carcinoma through the coordination of Hippo-Yap and PTEN-PI3K/AKT signaling pathways. Oncotarget 20 29299170
2014 The C-terminal domains of human neurofibromin and its budding yeast homologs Ira1 and Ira2 regulate the metaphase to anaphase transition. Cell cycle (Georgetown, Tex.) 20 25486365
2019 Wheat Bran for Colon Cancer Prevention: The Synergy between Phytochemical Alkylresorcinol C21 and Intestinal Microbial Metabolite Butyrate. Journal of agricultural and food chemistry 19 31675233
2018 TBL1XR1 promotes migration and invasion in osteosarcoma cells and is negatively regulated by miR-186-5p. American journal of cancer research 19 30662805
2017 De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity. Scientific reports 19 28588275
2021 Delayed Administration of Angiotensin Receptor (AT2R) Agonist C21 Improves Survival and Preserves Sensorimotor Outcomes in Female Diabetic Rats Post-Stroke through Modulation of Microglial Activation. International journal of molecular sciences 18 33572986
2021 TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway. Frontiers in cell and developmental biology 18 33708771
2017 Pierpont syndrome associated with the p.Tyr446Cys missense mutation in TBL1XR1. European journal of medical genetics 18 28687524
2011 Korean Red Ginseng Up-regulates C21-Steroid Hormone Metabolism via Cyp11a1 Gene in Senescent Rat Testes. Journal of ginseng research 18 23717070
1983 Progesterone C21 hydroxylation and steroid carboxylic acid biosynthesis in the rabbit. In vitro studies with endocrine, metabolic, and potential target tissues. Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire 18 6313164
2007 [Apoptosis induced by the C21 sterols in Baishouwu and its mechanism of action in hepatoma]. Yao xue xue bao = Acta pharmaceutica Sinica 17 17633201
2023 A phase 2 trial investigating the effects of the angiotensin II type 2 receptor agonist C21 in systemic sclerosis-related Raynaud's. Rheumatology (Oxford, England) 16 35894657
2022 Optimization of fermentation for γ-aminobutyric acid (GABA) production by yeast Kluyveromyces marxianus C21 in okara (soybean residue). Bioprocess and biosystems engineering 16 35179639
2016 SUMOylation of TBL1 and TBLR1 promotes androgen-independent prostate cancer cell growth. Oncotarget 15 27129164
2018 TBL1XR1 as a potential therapeutic target that promotes epithelial-mesenchymal transition in lung squamous cell carcinoma. Experimental and therapeutic medicine 14 30651768
2017 Expanding the spectrum of TBL1XR1 deletion: Report of a patient with brain and cardiac malformations. European journal of medical genetics 14 29038029
2016 Synthesis and biological activity of two pregnane derivatives with a triazole or imidazole ring at C-21. The Journal of steroid biochemistry and molecular biology 14 26924581
2016 C21 steroidal glycosides from the roots of Cynanchum paniculatum. Fitoterapia 14 27380712
2015 C21 steroidal glycosides from Cynanchum stauntonii induce apoptosis in HepG2 cells. Steroids 14 26708267
2022 Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML. Cell reports 13 35263585
2019 Acute promyelocytic leukemia with a cryptic insertion of RARA into TBL1XR1. Genes, chromosomes & cancer 13 31350930
2017 A heritable microduplication encompassing TBL1XR1 causes a genomic sister-disorder for the 3q26.32 microdeletion syndrome. American journal of medical genetics. Part A 13 28574232
2016 Bioactive Octahydroxylated C21 Steroids from the Root Bark of Lycium chinense. Journal of natural products 13 26982999
2016 Nuclear TBLR1 as an ER corepressor promotes cell proliferation, migration and invasion in breast and ovarian cancer. American journal of cancer research 13 27822424
2024 Two decades of a protooncogene TBL1XR1: from a transcription modulator to cancer therapeutic target. Frontiers in oncology 12 38347836
2021 Anticancer properties of caudatin and related C-21 steroidal glycosides from Cynanchum plants. Steroids 12 33945800
2020 C21 Fraction Refined from Marsdenia tenacissima-Induced Apoptosis is Enhanced by Suppression of Autophagy in Human Gastric Cell Lines. ACS omega 12 33043194
2020 A C21-steroidal derivative suppresses T-cell lymphoma in mice by inhibiting SIRT3 via SAP18-SIN3. Communications biology 12 33273692
2018 TBL1XR1 mutations in Pierpont syndrome are not restricted to the recurrent p.Tyr446Cys mutation. American journal of medical genetics. Part A 12 30365874
2017 Cytotoxic and apoptosis-inducing activity of C21 steroids from the roots of Cynanchum atratum. Steroids 12 28327355
2014 Novel TBL1XR1, EPHA7 and SLFN12 mutations in a Sezary syndrome patient discovered by whole exome sequencing. Experimental dermatology 12 24689486
2020 Genotype and Phenotype Correlations for TBL1XR1 in Neurodevelopmental Disorders. Journal of molecular neuroscience : MN 11 32524419

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