Affinage

THRA

Thyroid hormone receptor alpha · UniProt P10827

Round 2 corrected
Length
490 aa
Mass
54.8 kDa
Annotated
2026-04-28
130 papers in source corpus 58 papers cited in narrative 52 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

THRA encodes thyroid hormone receptor alpha (TRα), a ligand-dependent nuclear transcription factor that functions primarily as an RXRα heterodimer on direct-repeat thyroid hormone response elements to control programs of erythroid, neuronal, and skeletal differentiation (PMID:1310350, PMID:8385673, PMID:1972036). In the unliganded state, TRα recruits the corepressors N-CoR and SMRT together with HDAC3 to silence target genes; T3 binding triggers corepressor release and assembly of a multisubunit coactivator complex (TRAP/DRIP–Mediator) anchored by TRAP220/MED1 via LXXLL motifs, with additional recruitment of CBP, ACTR, and P/CAF providing coordinated histone acetyltransferase activity (PMID:7566114, PMID:8710870, PMID:9653119, PMID:9267036). Alternative splicing generates TRα2, a non-T3-binding isoform that acts as a dominant inhibitor of TRα1, and phosphorylation by CK2 (Ser12) and PKA/PKC (Ser28/29) further modulates receptor activity (PMID:2537467, PMID:2552374, PMID:2903825). Loss-of-function THRA mutations that reduce T3 binding affinity and impair corepressor release cause resistance to thyroid hormone alpha (RTHα), characterized by growth retardation, skeletal dysplasia, macrocephaly, and anemia (PMID:25670821, PMID:29205102).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1986 High

    Identification of c-erbA as a high-affinity T3/T4 receptor established that a known proto-oncogene is a nuclear hormone receptor, resolving the molecular identity of the thyroid hormone receptor.

    Evidence Hormone binding assays and nuclear localization studies comparing c-erbA and v-erbA proteins

    PMID:2879242 PMID:2879243

    Open questions at the time
    • No information on DNA target specificity
    • Structure of the receptor unknown
    • Mechanism of transcriptional regulation not addressed
  2. 1988 High

    Discovery of alternative splicing generating TRα2 (non-T3-binding) and identification of PKA/CK2 phosphorylation sites revealed two major regulatory axes—isoform diversity and post-translational modification—that modulate TRα function independently of ligand.

    Evidence cDNA cloning and in vitro T3 binding showing TRα2 lacks hormone binding; tryptic phosphopeptide mapping and in vitro kinase assays with purified PKA and CK2 identifying Ser12 and Ser28/29

    PMID:2537467 PMID:2552374 PMID:2903825

    Open questions at the time
    • Functional consequence of phosphorylation on transcriptional activity not determined
    • Physiological role of TRα2 in vivo unknown
    • No structural basis for why TRα2 cannot bind T3
  3. 1989 High

    Mapping the C-terminal activation domain and demonstrating that unliganded TRα is a transcriptional repressor (while T3 converts it to an activator) established the dual-function switch model and defined the functional importance of the AF-2 helix region.

    Evidence Chimeric v-erbA/c-erbA protein analysis, co-transfection reporter assays, and erythroid differentiation assays

    PMID:1972036 PMID:2733791 PMID:8098843

    Open questions at the time
    • No cofactors identified that mediate repression or activation
    • No structural model of the AF-2 region
    • Mechanism of AP-1 interference unclear
  4. 1992 High

    Demonstration that RXRα is the obligate heterodimerization partner for stable TRα DNA binding and transcriptional activity resolved how TRα engages response elements and explained why unliganded TRα can sequester RXR from RAR, suppressing retinoic acid signaling.

    Evidence Biochemical co-purification, EMSA, co-transfection reporter assays, and mutagenesis of the dimerization interface

    PMID:1310350 PMID:1314167 PMID:8096810

    Open questions at the time
    • Crystal structure of TRα/RXR heterodimer not available
    • In vivo relevance of RXR competition with RAR not established in genetic models
  5. 1995 High

    Identification of N-CoR and SMRT as corepressors that bind unliganded TRα and are released upon T3 binding provided the molecular basis for the repression-to-activation switch.

    Evidence Biochemical purification, co-immunoprecipitation, in vitro binding, and reporter gene assays

    PMID:7566114 PMID:7566127

    Open questions at the time
    • Chromatin context of corepressor recruitment not yet examined
    • Identity of the histone-modifying activity in the corepressor complex unknown
  6. 1996 High

    Purification of the TRAP coactivator complex from T3-treated cells and demonstration of CBP recruitment established that ligand-activated TRα assembles a multisubunit coactivator platform linking to general transcription machinery.

    Evidence Biochemical purification from HeLa cells, cell-free transcription assays on T3-responsive promoters, direct interaction assays for CBP

    PMID:8616895 PMID:8710870

    Open questions at the time
    • Subunit composition of TRAP complex not fully resolved
    • Sequential versus simultaneous coactivator recruitment not distinguished
  7. 1998 High

    Identification of TRAP220/MED1 as the LXXLL-motif-containing anchor subunit for TR, and of ACTR as a HAT-containing coactivator, completed the picture of a coordinated multi-HAT coactivator assembly (ACTR + CBP + P/CAF) recruited to TRα via TRAP220.

    Evidence Direct binding assays with LXXLL motif mutants, dominant negative TRAP220 fragments, purified ACTR HAT assays, cell-free transcription

    PMID:9267036 PMID:9653119

    Open questions at the time
    • Order of coactivator recruitment to endogenous chromatin not defined
    • No genome-wide map of TRα-occupied enhancers
  8. 2000 High

    ChIP-based demonstration that TRα and v-erbA recruit N-CoR with HDAC3 (excluding Sin3, HDAC1, Mi-2) on chromatinized templates in vivo defined the specific HDAC complex used for TRα-mediated repression.

    Evidence Xenopus oocyte ChIP, HDAC inhibitor treatment, in vitro TFIIB binding assays

    PMID:10921888

    Open questions at the time
    • Whether the same N-CoR/HDAC3 complex operates at mammalian endogenous loci not confirmed
    • No structural basis for selective HDAC3 recruitment over other HDACs
  9. 2015 Medium

    Discovery that loss-of-function THRA mutations cause resistance to thyroid hormone alpha (RTHα) in humans linked the molecular mechanism of impaired T3 binding and corepressor release to a defined clinical syndrome of growth retardation, skeletal dysplasia, and macrocephaly.

    Evidence Whole exome sequencing in patient cohorts, in vitro T3 binding and transcriptional assays of mutant TRα1

    PMID:25670821 PMID:26037512

    Open questions at the time
    • Small patient numbers limit genotype-phenotype generalization
    • Tissue-specific consequences of mutations not dissected
    • No rescue experiments in patient-derived cells
  10. 2018 High

    CRISPR-generated mouse models established that RTHα phenotype severity correlates directly with the degree to which mutant TRα1 retains corepressor binding in the presence of T3, providing a unifying mechanistic explanation for genotype-phenotype variability.

    Evidence CRISPR/Cas9 editing of mouse Thra with multiple alleles, phenotypic analysis, corepressor interaction assays ± T3

    PMID:29205102

    Open questions at the time
    • Whether pharmacological corepressor displacement can rescue phenotypes not tested
    • Contribution of non-genomic TRα signaling to RTHα phenotype unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The genome-wide chromatin landscape of TRα1 occupancy, the structural basis of isoform-specific coactivator/corepressor selectivity, and the physiological role of TRα2 in vivo remain incompletely resolved.
  • No genome-wide ChIP-seq map of endogenous TRα1 binding in key tissues
  • TRα2 knockout phenotype not fully characterized
  • Structural basis for HDAC3-selective recruitment unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
CREBBPHDAC3MED1NCOA3NCOR1NCOR2NR0B2RXRA
Complex memberships
N-CoR/SMRT/HDAC3 corepressor complexTRAP/Mediator complexTRα/RXRα heterodimer

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 The c-erb-A protein was identified as a high-affinity receptor for thyroid hormone (T3/T4). The protein is nuclear-localized and binds to DNA, while the viral oncogene product v-erb-A is defective in hormone binding but retains nuclear localization. Hormone binding assays, nuclear localization studies, comparison of c-erbA and v-erbA proteins Nature High 2879242 2879243
1987 A novel thyroid hormone receptor (erbA-T/TRα) encoded by a human testis cDNA clone was shown to bind T3 with high affinity (Kd ~0.38 nM), establishing that multiple human thyroid hormone receptor isoforms exist with potentially different tissue specificities. cDNA cloning, in vitro binding assay (T3 binding with Scatchard analysis) Science High 3672126
1988 The c-erbA alpha-encoded thyroid hormone receptor (TRα) is phosphorylated on serine residues at two distinct sites in its amino-terminal domain. Activation of either protein kinase C (PKC) or cAMP-dependent protein kinase (PKA) enhances phosphorylation at one shared site (Ser28/29), and PKA phosphorylates this site directly in vitro, identifying PKA as a writer of TRα phosphorylation. In vivo phosphorylation labeling, tryptic phosphopeptide mapping, in vitro kinase assay with purified PKA The EMBO journal High 2903825
1988 Alternative splicing of the rat c-erbA alpha (Thra) primary transcript generates r-erbA alpha-2, a protein that retains the DNA-binding domain but lacks T3-binding capacity, and which inhibits T3-dependent transcriptional activation by functional T3 receptors (r-erbA alpha-1 and r-erbA beta). cDNA cloning, in vitro T3 binding assay, transient transfection reporter assay Nature High 2537467 2554288 2903438
1988 The hormone-binding domain of chicken c-erbA (TRα) resides in the carboxy-terminal half of the protein. Multiple mutations present in the carboxy-terminal half of v-erbA cooperate to abolish hormone binding, and a point mutation between the DNA- and ligand-binding domains that abolishes v-erbA biological activity does not affect hormone binding, indicating this region controls transcriptional activity independently of hormone binding. Chimeric c-erbA/v-erbA protein analysis, in vitro T3 binding assay, site-directed mutagenesis The EMBO journal High 3359993
1988 Both c-erbA-alpha (chicken) and c-erbA-beta (human placenta) can function as hormone-dependent modulators of thyroid-hormone-responsive genes (rat GH and PRL). In receptor-deficient cells both act as classical T3 receptors, while in receptor-containing cells they modulate transcription in a hormone-independent manner, demonstrating that events other than ligand binding can activate TRα. Transient transfection reporter assays in multiple cell lines (receptor-deficient and receptor-containing) Molecular endocrinology Medium 2903439
1989 The v-erbA oncogene protein acts as a constitutive transcriptional repressor and dominant negative antagonist of the thyroid hormone receptor (TRα/c-erbA): when coexpressed with TRα, v-erbA blocks thyroid hormone-induced gene activation. Unliganded TRα itself suppresses responsive promoter activity, but hormone converts it to an activator. Transient co-transfection reporter assays; dominant negative functional analysis Nature High 2733791
1989 The c-erbA alpha (THRA) gene locus on chromosome 17 encodes both TRα1 and TRα2 (via alternative splicing) and overlaps with the Rev-ErbA alpha gene, which is encoded on the opposite DNA strand. A 269-bp segment is exonic in both Rev-ErbA alpha and r-erbA alpha-2 mRNAs, generating complementary RNAs from the same genomic locus. Genomic DNA isolation and sequencing, cDNA cloning, Northern blotting, exon mapping Molecular and cellular biology High 2539258 2542765
1989 c-ErbA alpha (TRα) represses AP-1-mediated transcriptional activation of the interstitial collagenase gene promoter by decreasing AP-1 transcription factor activity in a ligand-activated manner. v-ErbA fails to repress AP-1 and instead acts as a dominant negative by overcoming this repression, maintaining a fully active AP-1 complex. Transient transfection reporter assays, AP-1 activity assays, dominant negative analysis Cell High 1682056
1989 c-erbA alpha (TRα) phosphorylated on serine 12 by casein kinase II (CK2) in vitro at a site matching the consensus CK2 substrate motif with flanking acidic residues. Site-directed mutagenesis (Ser12→Ala) abolished CK2 phosphorylation in vitro, identifying CK2 as the kinase for this N-terminal site. The CK2-phosphorylated serine 12 is conserved across all T3-binding c-erbA alpha family members but absent in v-erbA. In vitro kinase assay with purified CK2, two-dimensional phosphopeptide mapping, site-directed mutagenesis Oncogene High 2552374
1990 v-erbA oncoprotein requires phosphorylation at Ser-16/17 (in its v-erbA-encoded domain, corresponding to the PKA/PKC phosphorylation site of c-erbA) for its oncogenic function. Ser→Ala substitution abolished phosphorylation and eliminated the ability to block erythroid differentiation and repress erythrocyte-specific genes (band 3, carbonic anhydrase II), while Ser→Thr preserved basal but not PKA/PKC-enhanced phosphorylation and yielded partial activity. H7 kinase inhibitor recapitulated the differentiation-induction phenotype. Site-directed mutagenesis, in vivo phosphorylation assay, biological differentiation assay in transformed erythroblasts, protein kinase inhibitor treatment Genes & development High 1979040
1990 Overexpressed c-erbA (TRα) modulates erythroid differentiation and erythrocyte-specific gene expression in a T3-dependent fashion in erythroid cells. The v-erbA oncoprotein has lost this hormone-dependent regulatory function. Chimeric v-/c-erbA analysis mapped the loss-of-function to the very C-terminus of c-erbA, encompassing a cluster of conserved amino acids with the potential to form an amphipathic alpha-helix. Retroviral expression, chimeric protein analysis, erythroid differentiation assays, gene expression analysis Cell High 1972036
1990 The v-erbA protein specifically suppresses transcription of the avian erythrocyte anion transporter (band 3) gene at the transcriptional level, establishing band 3 as a direct transcriptional target of v-erbA/TRα. This repression correlates with, and contributes to, the differentiation block caused by v-erbA. Retroviral expression, transcription assays, alkaline pH rescue experiment, pharmacological inhibition of band 3 Cell High 2830979
1990 In S. cerevisiae, the v-erbA protein unexpectedly acts as a hormone-regulated transcriptional activator rather than a repressor, demonstrating that the repressor activity of v-erbA in animal cells requires interaction with, or modification by, specific cellular factors absent in yeast. This establishes that TRα/v-erbA transcriptional activity is determined by cellular context. Yeast transcriptional activation assay, hormone treatment, cross-species comparison Cell Medium 1979758
1991 The human THRA gene (c-erbA-1) is organized in 10 exons spanning ~27 kb on chromosome 17. Each zinc finger of the DNA-binding domain is encoded by a separate exon; the hormone-binding domain is assembled from three exons. The last two exons are alternatively spliced to generate TRα1 and TRα2 mRNAs. The genomic locus also encodes the oppositely transcribed ear-1/Rev-ErbA. Genomic DNA cloning, restriction mapping, exon sequencing, comparison with chicken gene Nucleic acids research High 1850510
1991 A 269-bp complementary RNA (antisense to c-erbA alpha-2 mRNA), representing the 3' end of Rev-ErbA alpha mRNA, inhibits splicing of alpha-2 pre-mRNA in vitro, demonstrating that antisense RNA base-pairing can regulate alternative splicing of the Thra locus to favor formation of alpha-1 (TRα1) over alpha-2 mRNA. In vitro splicing assay with added antisense RNA, competition with sense/antisense controls The Journal of biological chemistry High 1657988
1991 v-erbA overexpression is required to extinguish c-erbA (TRα) function in erythroid cells. When v-erbA and c-erbA are coexpressed at approximately equimolar levels, c-erbA activity is dominant: T3 induces erythroid differentiation and activates CAII transcription via a direct erbA-binding site in the CAII promoter. Very high v-erbA concentrations are required to suppress c-erbA-dependent activation. Stable co-expression in erythroblasts, T3 treatment, reporter gene assays with CAII erbA-binding site, differentiation assays Genes & development High 1682217
1991 A single point mutation in the DNA-binding zinc finger domain differentiates v-erbA from c-erbA (TRα): back-mutation of this viral residue to the c-erbA sequence severely impairs erythroid transformation and produces subtle changes in DNA binding, indicating that altered DNA-binding specificity contributes to v-erbA oncogenic activation. Site-directed mutagenesis (back-mutation), erythroid transformation assay, EMSA/DNA binding assay Journal of virology Medium 1672166
1991 c-erbA alpha (TRα) and retinoic acid receptor alpha (RARα) cooperate in modulating normal erythroid differentiation. T3 and retinoic acid act synergistically, and the receptor dimerization domain of TRα is required for this functional cooperation, suggesting TRα/RARα heterodimers regulate erythroid differentiation. Primary erythroid progenitor culture, ligand treatment, retroviral receptor overexpression, genetic analysis with dimerization-domain mutants Oncogene Medium 1347914
1992 Retinoid X receptor alpha (RXRα) is a required dimerization partner for thyroid hormone receptor (TRα) for stable DNA binding. RXRα co-purifies with TRα, forms heterodimers in solution, and greatly enhances TRα transcriptional activity. TRα is a monomer in solution and cannot form stable homodimeric complexes on response elements without RXRα. Biochemical co-purification, solution binding assays, EMSA, co-transfection reporter assays Nature / The EMBO journal High 1310350 1314167
1993 A conserved 9-amino acid sequence at the extreme carboxy terminus of c-ErbA alpha (TRα), which is deleted in v-ErbA, is essential for T3-dependent transcriptional activation, AP-1 interference, and induction of erythroid differentiation. Single, double, and triple amino acid substitutions within this region abolish all these activities and reduce T3 binding, but a chimera with similarly reduced T3 binding retains function, showing the C-terminal domain has a role beyond just hormone binding. c-ErbA/v-ErbA chimera analysis, site-directed mutagenesis, reporter assays, differentiation assays Molecular and cellular biology High 8098843
1993 c-ErbA alpha (TRα) can act as a ligand-independent transcriptional activator through a novel RSV-T3RE response element, distinct from classical T3REs. This activation utilizes a unique N-terminal activation domain and involves either TRα homodimers or TRα/RXR heterodimers. Ligand (T3) reverses activation through this element. DNA binding to the RSV-T3RE induces a different TRα conformation than binding to classical T3REs, demonstrating response-element-directed selective deployment of activation domains. Transient transfection reporter assays, RXR co-transfection, deletion mutagenesis of activation domains Cell High 7903219
1993 c-erbA alpha (TRα) and v-erbA both enhance c-Jun transcriptional activation in certain promoter contexts, acting as co-activators of AP-1. This reveals a positive transcriptional function for TRα/v-erbA through cooperative interaction with c-Jun, distinct from their repressor activities. Transient co-transfection reporter assays with c-Jun, c-Fos, c-erbA, v-erbA Oncogene Medium 1349165
1993 c-erbA alpha (TRα) promoter is a TATA-less, GC-rich promoter containing multiple Sp1 sites. Glucocorticoid (dexamethasone) enhances THRA promoter activity, but thyroid hormone does not, establishing autoregulation of THRA gene expression is not mediated via its own promoter. Transfection of CAT reporter constructs driven by human THRA promoter, hormone treatment of HeLa cells Oncogene Medium 8455948
1993 Stable expression of unliganded c-erbA alpha (TRα1) in mouse neuroblastoma N2a cells induces trkB mRNA expression and protein (gp145trkB) that is phosphorylated on tyrosine in response to BDNF, while concomitantly suppressing trkA and trkC. This TRα1-driven trkB induction is ligand-independent and is also produced by transient expression of TRβ1, indicating a conserved function of unliganded TR in regulating neurotrophin receptor expression. Stable transfection, Northern blot, Western blot, tyrosine phosphorylation assay, BDNF stimulation Oncogene Medium 8134111
1993 v-erbA oncogenic function in neoplasia best correlates not with suppression of c-erbA/TRα action but with its ability to interfere with retinoic acid receptor (RAR) signaling. v-erbA forms heterodimers with RXR, which dramatically interferes with RXR transcriptional activity. In contrast, v-erbA interferes with thyroid hormone and trans-retinoic acid receptors by competing for DNA response elements, without observable heterodimerization. Co-transfection reporter assays, EMSA for heterodimerization, correlation of transformation with receptor interference Cell / Molecular and cellular biology High 1679679 8105369
1993 Unliganded TRα (c-erbA), but not v-erbA, suppresses RAR-dependent transactivation by titrating out the common dimerization partner RXR. TRα competes with RAR for RXR and dissociates preformed RAR/RXR-RARE complexes in vitro. A single point mutation in the TRα dimerization interface (equivalent to the v-erbA Pro349 position) abolishes this trans-dominant suppression, demonstrating that RXR competition is the mechanism. Co-transfection reporter assays, in vitro EMSA competition, site-directed mutagenesis of dimerization domain The EMBO journal High 8096810
1994 c-erbA alpha (TRα) and RARα control commitment of hematopoietic self-renewing progenitor cells to apoptosis or differentiation; both T3 and RA induce apoptosis and strong inhibition of self-renewal in progenitor cells. The v-erbA oncogene renders erythrocytic progenitor cells insensitive to apoptosis and self-renewal inhibition induced by RA or T3, through its transforming activity. Normal erythrocytic progenitor culture, ligand treatment, apoptosis and self-renewal assays, v-erbA retroviral expression Oncogene Medium 7906409
1994 TRα (c-erbA alpha/TR alpha-1) expressed in the adrenal medulla progenitor cell line PC12 inhibits NGF-induced neuronal differentiation and represses neuron-specific gene expression in the absence of T3, while permitting normal differentiation in the presence of T3. In the absence of T3, TRα-expressing cells become NGF-responsive for proliferation. TRα also constitutively blocks dexamethasone-induced chromaffin differentiation, revealing a role for TRα in controlling progenitor commitment. Stable retroviral expression of TRα in PC12 cells, NGF and T3 treatment, differentiation and gene expression assays The Journal of cell biology Medium 8385673
1994 v-erbA binds as homodimers to thyroid hormone response elements (TREs), and forms heterodimers with RXR, T3 receptor auxiliary protein (TRAP), and TRα. High concentrations of T3 decrease v-erbA homodimer binding to TREs. Multiple v-erbA complexes (homodimers, heterodimers with RXR/TRAP/TRα) all remain bound to DNA in the presence of T3 and can compete with TR-containing complexes, contributing to dominant negative effects. EMSA with in vitro translated proteins, co-transfection reporter assays The Journal of biological chemistry Medium 7904604
1994 c-ErbA (TRα) but not v-ErbA forms heterodimers with RXR that compete with the erythrocyte-specific nuclear factor NFX for binding to the CAII promoter PAL2 site. This competition displaces the repressor NFX, providing a mechanism by which T3-activated TRα/RXR activates CAII transcription. v-ErbA alone or with RXR fails to compete with NFX, explaining why v-ErbA cannot activate CAII. EMSA competition assays, transfection reporter assays, identification of NFX erythrocyte-specific factor Oncogene Medium 7916146
1995 A nuclear receptor co-repressor (N-CoR) of ~270 kDa physically interacts with thyroid hormone receptor (TRα) and mediates ligand-independent transcriptional repression. N-CoR association with TR is destabilized by T3, providing a molecular mechanism for unliganded TR repression and ligand-induced de-repression. Biochemical purification, co-immunoprecipitation, in vitro protein binding, reporter gene assays Nature High 7566114 7566127
1995 SMRT (silencing mediator for retinoid and thyroid-hormone receptors) was identified as a corepressor that interacts with thyroid hormone receptor (TRα) in solution and when bound to DNA response elements. This association is destabilized by ligand. In vivo SMRT functions as a potent corepressor of TR-mediated transcription. Protein interaction screen, co-immunoprecipitation, reporter assays, GAL4 fusion repressor assays Nature High 7566127
1995 Two classes of TR-interacting proteins (TRIPs) were identified by yeast interaction trap: one class interacts with TRβ ligand-binding domain only in the presence of T3 (putative coactivators), another only in its absence (putative corepressors). Neither class interacts with glucocorticoid receptor. Trip4 contains a transcriptional activation domain; Trip9/10 confer indirect T3-dependent activation when co-expressed with TR and RXR in yeast. Yeast interaction trap, in vitro binding, yeast reporter assays Molecular endocrinology Medium 7776974
1996 CBP (CREB-binding protein) directly interacts with the ligand-binding domain of multiple nuclear receptors including TRα, and this interaction is required for ligand-dependent transcriptional activation. CBP also interacts with p160 coactivators (SRC-1 variants). Competition between nuclear receptors and AP-1 for limiting amounts of CBP/p300 underlies AP-1 inhibition by TRα. Direct protein interaction assays, co-immunoprecipitation, reporter assays, dominant negative CBP competition Cell High 8616895
1996 TRα purified from HeLa cells grown in the presence of T3 is associated with a group of nuclear proteins termed thyroid hormone receptor-associated proteins (TRAPs), forming a ligand-induced multisubunit coactivator complex. This TR/TRAP complex markedly activates transcription from T3-responsive promoters in cell-free assays. TRα purified without T3 lacks TRAPs and shows only low-level, ligand-dependent activation. RXR is required for TRAP complex function but is not a TRAP component. Biochemical purification from HeLa cells, in vitro transcription reconstitution, T3-dependent complex assembly Proceedings of the National Academy of Sciences of the United States of America High 8710870
1996 SHP (short heterodimer partner), an orphan nuclear receptor lacking a DNA-binding domain, interacts directly with the thyroid hormone receptor (TRα) via its ligand-binding/dimerization domain in yeast two-hybrid and in vitro binding assays. SHP specifically inhibits TR-dependent transactivation in mammalian cells, functioning as a negative regulator of TR signaling. Yeast two-hybrid, in vitro binding assay, co-transfection reporter assay Science Medium 8650544
1997 ACTR, a nuclear receptor coactivator, directly binds TRα (and other nuclear receptors) in a hormone-dependent manner and recruits CBP and P/CAF to form a multisubunit coactivator complex. ACTR itself possesses intrinsic histone acetyltransferase (HAT) activity, establishing that TRα activation involves coordinated HAT activity from at least three enzymes (ACTR, CBP, P/CAF). Direct protein binding assays, co-immunoprecipitation, in vitro HAT assay with purified ACTR Cell High 9267036
1997 v-ErbA can substitute for the ligand-activated glucocorticoid receptor (GR) and estrogen receptor (ER) to induce proliferation and arrest differentiation of erythroid progenitors, and requires cooperation with c-Kit (receptor tyrosine kinase) for both activities. v-ErbA's biological activities depend on distinct mutations in the DNA-binding domain. v-ErbA acts as a weak, partial repressor of c-ErbA/TRα function (not fully dominant negative) in normal erythroblasts; full dominant-negative activity requires restoration of RXR heterodimerization capacity. Retroviral expression in erythroid progenitors, GR/ER antagonist treatment, c-Kit dependency analysis, RXR heterodimerization mutant rescue Oncogene Medium 9264411
1998 TRAP220, a component of the TRAP coactivator complex, directly interacts with TRα (and other nuclear receptors) in a ligand-dependent manner through its LXXLL motifs engaging the C-terminus of TRα. A fragment containing LXXLL motifs acts as a dominant negative inhibitor of nuclear receptor-mediated transcription. TRAP220 plays a central role in anchoring other TRAPs to TRα. Co-immunoprecipitation, direct binding assays, transfection reporter assays, cell-free transcription assays Proceedings of the National Academy of Sciences of the United States of America High 9653119
1998 NSD1, a novel nuclear protein with SET domain and PHD fingers, contains two distinct TR interaction domains (NID-L and NID+L) with opposing properties: NID-L interacts with unliganded TRα LBD (requiring helix 1 integrity, like corepressors), while NID+L interacts with liganded TRα LBD (requiring helix 12, like coactivators). NSD1 contains both repression and activation domains, functioning as a bifunctional transcriptional intermediary factor. Yeast two-hybrid, in vitro pull-down with defined LBD mutants, transient transfection reporter assays The EMBO journal High 9628876
1998 v-ErbA constitutively binds to the carbonic anhydrase II (CAII) gene intronic erythroid enhancer element (HS2-VRE) in vivo in transformed undifferentiated erythroblasts, as shown by in vivo footprinting. This binding co-occurs with GATA-1. Treatment with histone deacetylase inhibitor trichostatin A derepresses the chromatin-embedded endogenous CAII gene but not a transfected construct, demonstrating that HDAC activity is required for v-ErbA repression at the endogenous chromatin-embedded locus. In vivo footprinting, retroviral expression assays, trichostatin A treatment, transfection assays The EMBO journal High 9857194
1999 The TRAP complex (thyroid hormone receptor-associated proteins) is virtually identical to the SMCC (SRB- and MED-containing cofactor complex) that mediates transcriptional activation by p53. TRAP80 directly interacts with p53 and VP16 activation domains. The TRAP220/SMCC220 subunit binds liganded TRα. This establishes that TRα and other activators share a common coactivator complex targeting RNA Pol II. Mass spectrometry of purified complexes, direct protein binding assays, reporter assays Molecular cell High 10198638
1999 Ligand-dependent activation by TRα requires the DRIP complex (distinct from TRAP only by nomenclature in context of VDR). The DRIP complex mediates ligand-dependent enhancement of transcription by TRα in cell-free transcription assays on chromatin templates, establishing DRIPs as positive coactivators for TRα. Cell-free transcription assay on chromatin templates, biochemical purification of DRIP complex Nature High 10235266
2000 v-ErbA and TRα both recruit N-CoR and concomitantly HDAC3 (without association with Sin3, HDAC1/RPD3, Mi-2, or HDAC5) on thyroid hormone-responsive templates in Xenopus oocytes. v-ErbA repression is more HDAC-inhibitor sensitive than TRα repression and requires mature chromatin (v-ErbA cannot repress on partly chromatinized templates). v-ErbA is less competent than TRα for binding TFIIB in vitro and in vivo, explaining reduced repression on non-chromatinized templates. Xenopus oocyte injection, chromatin immunoprecipitation, HDAC inhibitor treatment, in vitro TFIIB binding assay The EMBO journal High 10921888
2001 A targeted mutation (Thra(tm2)) in the mouse Thra gene that deletes TRα2 and causes overexpression of TRα1 suppresses deafness and thyroid hyperactivity phenotypes caused by Thrb-null mutation. This demonstrates that increased TRα1 expression can functionally substitute for TRβ in auditory and thyroid functions, revealing significant functional overlap between TR isotypes. Mouse genetics (targeted deletion), auditory threshold testing, thyroid function assays, genetic epistasis in double-mutant mice Human molecular genetics High 11726557
2005 v-ErbA dimerizes with TRα and RXR and sequesters a significant fraction of both nuclear receptors in the cytoplasm, partially reversing their normal nuclear localization. Ligand and histone deacetylase inhibitor (trichostatin A) partially restore TRα nuclear localization. This defines cytoplasmic sequestration as an additional dominant-negative mechanism for v-ErbA distinct from DNA competition. Subcellular fractionation, co-immunoprecipitation, immunofluorescence microscopy, histone deacetylase inhibitor treatment Molecular endocrinology Medium 15650025
2009 T3 activates PI3-kinase via Src kinase signaling through an αvβ3 integrin receptor, and PI3-kinase activity mediates shuttling of nuclear TRα from cytoplasm to nucleus. LY-294002 (PI3-kinase inhibitor) blocks T3-induced TRα nuclear translocation and HIF-1α mRNA accumulation. This establishes a non-genomic T3 signaling pathway regulating TRα subcellular localization. PI3-kinase inhibitor treatment, siRNA knockdown of PI3-kinase, subcellular localization assays, integrin antagonist experiments American journal of physiology. Cell physiology Medium 19158403
2015 Truncating and missense mutations in the THRA gene cause resistance to thyroid hormone alpha (RTHα) with a consistent phenotype including growth retardation, macrocephaly, skeletal dysplasia, mental retardation, low fT4/high fT3 ratio, and anemia. A genotype-phenotype correlation was established: truncating mutations cause more severe phenotypes than missense mutations. Whole exome sequencing identified THRA as the causative gene. Whole exome sequencing, Sanger sequencing confirmation, clinical/biochemical characterization of 6 patients from 5 families Journal of medical genetics Medium 25670821
2015 A de novo missense mutation in THRA (N359Y) affecting TRα1 causes RTHα with severe bone malformation, dwarfism, and macrocytic anemia. The mutant TRα1(N359Y) has decreased T3 binding affinity and dominant-negative effect on wild-type TRα1 in transcriptional assays, with low resting energy expenditure normalized by T3 treatment. Whole exome sequencing, in vitro transcription assay, T3 binding assay, clinical T3 treatment trial The Journal of clinical endocrinology and metabolism Medium 26037512
2018 CRISPR/Cas9 editing of the mouse Thra gene producing frameshift or missense mutations recapitulates human RTHα with variable phenotype severity. Phenotype severity correlates with the ability of the mutant TRα1 to interact with transcriptional corepressors in the presence of thyroid hormone (i.e., corepressor release by T3 is impaired in proportion to severity). CRISPR/Cas9 genome editing, mouse phenotypic analysis, corepressor interaction assay in presence/absence of T3 Thyroid High 29205102
2019 THRA missense mutations M259T and T273A in RTHα patients reduce TRα1 affinity for T3, such that corepressors fail to dissociate from the mutant receptor even in the presence of T3. In silico modeling combined with T3 binding assays and corepressor interaction assays demonstrates that the severity of RTHα correlates with reduction in T3 binding affinity and the consequent inability to release corepressors. Biochemical T3 binding assays, corepressor interaction assays, in silico structural modeling, cellular transcriptional assays Thyroid Medium 32204686

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 1894 8616895
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
1995 Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 1694 7566114
1995 A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 1679 7566127
1986 The c-erb-A gene encodes a thyroid hormone receptor. Nature 1504 2879243
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1986 The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature 1317 2879242
1997 Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell 1255 9267036
2009 A census of human transcription factors: function, expression and evolution. Nature reviews. Genetics 1191 19274049
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
1992 Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature 932 1310350
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1986 The chicken oestrogen receptor sequence: homology with v-erbA and the human oestrogen and glucocorticoid receptors. The EMBO journal 645 3755102
1989 Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist. Nature 616 2733791
1999 Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 583 10235266
2010 An atlas of combinatorial transcriptional regulation in mouse and man. Cell 573 20211142
2003 Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. The Journal of biological chemistry 554 12871948
1996 Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proceedings of the National Academy of Sciences of the United States of America 466 8710870
1996 An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Science (New York, N.Y.) 441 8650544
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1992 RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors. The EMBO journal 433 1314167
1989 Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing. Nature 433 2537467
1995 Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor. Molecular endocrinology (Baltimore, Md.) 408 7776974
1998 The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion. Proceedings of the National Academy of Sciences of the United States of America 381 9653119
1987 Amplification of the neu (c-erbB-2) oncogene in human mammmary tumors is relatively frequent and is often accompanied by amplification of the linked c-erbA oncogene. Molecular and cellular biology 368 3299059
1999 Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Molecular cell 353 10198638
2006 An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature 335 16799563
1988 Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone. Proceedings of the National Academy of Sciences of the United States of America 312 2901090
1989 A novel member of the thyroid/steroid hormone receptor family is encoded by the opposite strand of the rat c-erbA alpha transcriptional unit. Molecular and cellular biology 309 2542765
1983 Transforming capacities of avian erythroblastosis virus mutants deleted in the erbA or erbB oncogenes. Cell 300 6297784
1988 Genetic alterations of the c-erbB-2 oncogene occur frequently in tubular adenocarcinoma of the stomach and are often accompanied by amplification of the v-erbA homologue. Oncogene 284 3281095
1990 Relationship of c-erbA mRNA content to tissue triiodothyronine nuclear binding capacity and function in developing and adult rats. The Journal of biological chemistry 283 2162351
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
1988 Identification of a rat c-erbA alpha-related protein which binds deoxyribonucleic acid but does not bind thyroid hormone. Molecular endocrinology (Baltimore, Md.) 275 2903438
1990 Differential and tissue-specific regulation of the multiple rat c-erbA messenger RNA species by thyroid hormone. The Journal of clinical investigation 249 2153150
1989 Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus. Cell 244 2539258
1990 v-erbA oncogene activation entails the loss of hormone-dependent regulator activity of c-erbA. Cell 240 1972036
1987 A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library. Science (New York, N.Y.) 237 3672126
1991 Characterization of seven novel mutations of the c-erbA beta gene in unrelated kindreds with generalized thyroid hormone resistance. Evidence for two "hot spot" regions of the ligand binding domain. The Journal of clinical investigation 234 1661299
1998 Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators. The EMBO journal 218 9628876
1988 Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other. Nucleic acids research 212 2905047
2009 L-Thyroxine vs. 3,5,3'-triiodo-L-thyronine and cell proliferation: activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. American journal of physiology. Cell physiology 208 19158403
1993 The orphan receptor Rev-ErbA alpha activates transcription via a novel response element. Molecular and cellular biology 208 8474464
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
1984 Chromosomal localisation of the human homologues to the oncogenes erbA and B. The EMBO journal 199 6323162
1991 Independent expression of the alpha and beta c-erbA genes in developing rat brain. Molecular endocrinology (Baltimore, Md.) 194 1663215
1990 A base mutation of the C-erbA beta thyroid hormone receptor in a kindred with generalized thyroid hormone resistance. Molecular heterogeneity in two other kindreds. The Journal of clinical investigation 178 2153155
1988 Tight linkage between the syndrome of generalized thyroid hormone resistance and the human c-erbA beta gene. Molecular endocrinology (Baltimore, Md.) 160 2905763
1991 A novel mechanism of action for v-ErbA: abrogation of the inactivation of transcription factor AP-1 by retinoic acid and thyroid hormone receptors. Cell 159 1682056
1986 v-erbA cooperates with sarcoma oncogenes in leukemic cell transformation. Cell 159 3009024
1988 v-erbA specifically suppresses transcription of the avian erythrocyte anion transporter (band 3) gene. Cell 157 2830979
1988 Activation of protein kinase C or cAMP-dependent protein kinase increases phosphorylation of the c-erbA-encoded thyroid hormone receptor and of the v-erbA-encoded protein. The EMBO journal 155 2903825
1991 Inhibition of c-erbA mRNA splicing by a naturally occurring antisense RNA. The Journal of biological chemistry 149 1657988
1988 c-erbA protooncogenes mediate thyroid hormone-dependent and independent regulation of the rat growth hormone and prolactin genes. Molecular endocrinology (Baltimore, Md.) 147 2903439
1984 A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America 141 6589608
1989 Human carboxyl-terminal variant of alpha-type c-erbA inhibits trans-activation by thyroid hormone receptors without binding thyroid hormone. Proceedings of the National Academy of Sciences of the United States of America 134 2554288
1988 Characterization of the hormone-binding domain of the chicken c-erbA/thyroid hormone receptor protein. The EMBO journal 127 3359993
1989 Presence of two members of c-erbA receptor gene family (c-erbA beta and c-erbA2) in smallest region of somatic homozygosity on chromosome 3p21-p25 in human breast carcinoma. Journal of the National Cancer Institute 126 2573734
1993 A novel cis element mediating ligand-independent activation by c-ErbA: implications for hormonal regulation. Cell 120 7903219
1991 v-erbA oncogene function in neoplasia correlates with its ability to repress retinoic acid receptor action. Cell 119 1679679
1987 Expression of the v-erbA oncogene in chicken embryo fibroblasts stimulates their proliferation in vitro and enhances tumor growth in vivo. Cell 113 2884040
1991 Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene. Nucleic acids research 106 1850510
1984 Sequencing the erbA gene of avian erythroblastosis virus reveals a new type of oncogene. Science (New York, N.Y.) 103 6328658
1993 A conserved C-terminal sequence that is deleted in v-ErbA is essential for the biological activities of c-ErbA (the thyroid hormone receptor). Molecular and cellular biology 102 8098843
2002 Expression of thyroid hormone receptor/erbA genes is altered in human breast cancer. Oncogene 98 12082618
1989 Expression of the v-erbA product, an altered nuclear hormone receptor, is sufficient to transform erythrocytic cells in vitro. Cell 98 2568887
2000 Increased cell death and delayed development in the cerebellum of mice lacking the rev-erbA(alpha) orphan receptor. Development (Cambridge, England) 97 10704394
1993 Unliganded T3R, but not its oncogenic variant, v-erbA, suppresses RAR-dependent transactivation by titrating out RXR. The EMBO journal 92 8096810
1992 Modulation of normal erythroid differentiation by the endogenous thyroid hormone and retinoic acid receptors: a possible target for v-erbA oncogene action. Oncogene 92 1347914
1987 A single point mutation in erbA restores the erythroid transforming potential of a mutant avian erythroblastosis virus (AEV) defective in both erbA and erbB oncogenes. The EMBO journal 92 2884103
1991 v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII. Genes & development 89 1682217
1990 Phosphorylation of the v-erbA protein is required for its function as an oncogene. Genes & development 89 1979040
1990 The viral erbA oncogene protein, a constitutive repressor in animal cells, is a hormone-regulated activator in yeast. Cell 87 1979758
1989 The c-erbA alpha-encoded thyroid hormone receptor is phosphorylated in its amino terminal domain by casein kinase II. Oncogene 86 2552374
1980 Nucleotide sequence of the thrA gene of Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America 86 7003595
1989 c-erbB-2/c-erbA co-amplification indicative of lymph node metastasis, and c-myc amplification of high tumour grade, in human breast carcinoma. British journal of cancer 81 2572268
1996 Two receptor interaction domains in the corepressor, N-CoR/RIP13, are required for an efficient interaction with Rev-erbA alpha and RVR: physical association is dependent on the E region of the orphan receptors. Nucleic acids research 79 8948627
1994 Thyroid abnormalities and hepatocellular carcinoma in mice transgenic for v-erbA. The EMBO journal 76 7925269
1993 v-erbA and citral reduce the teratogenic effects of all-trans retinoic acid and retinol, respectively, in Xenopus embryogenesis. Development (Cambridge, England) 76 7910550
1993 Thyroid hormone receptor/c-erbA: control of commitment and differentiation in the neuronal/chromaffin progenitor line PC12. The Journal of cell biology 76 8385673
1988 Regulation of two c-erbA messenger ribonucleic acids in rat GH3 cells by thyroid hormone. Molecular endocrinology (Baltimore, Md.) 72 2901667
2015 Thyroid hormone resistance syndrome due to mutations in the thyroid hormone receptor α gene (THRA). Journal of medical genetics 69 25670821
1991 A new point mutation in the 3,5,3'-triiodothyronine-binding domain of the c-erbA beta thyroid hormone receptor is tightly linked to generalized thyroid hormone resistance. The Journal of clinical endocrinology and metabolism 67 1846005
1994 c-erbA alpha/T3R and RARs control commitment of hematopoietic self-renewing progenitor cells to apoptosis or differentiation and are antagonized by the v-erbA oncogene. Oncogene 61 7906409
2000 Targeting of N-CoR and histone deacetylase 3 by the oncoprotein v-erbA yields a chromatin infrastructure-dependent transcriptional repression pathway. The EMBO journal 59 10921888
1993 The erbA oncogene represses the actions of both retinoid X and retinoid A receptors but does so by distinct mechanisms. Molecular and cellular biology 56 8105369
1992 Transcriptional repression of band 3 and CAII in v-erbA transformed erythroblasts accounts for an important part of the leukaemic phenotype. The EMBO journal 56 1354613
2000 Structure-function analysis of the Rev-erbA and RVR ligand-binding domains reveals a large hydrophobic surface that mediates corepressor binding and a ligand cavity occupied by side chains. Molecular endocrinology (Baltimore, Md.) 55 10809233
1991 Regulation of c-erbA-alpha messenger RNA species in tadpole erythrocytes by thyroid hormone. Molecular endocrinology (Baltimore, Md.) 54 1645454
1992 The v-erbA oncogene requires cooperation with tyrosine kinases to arrest erythroid differentiation induced by ligand-activated endogenous c-erbA and retinoic acid receptor. Oncogene 53 1347913
1991 The thyroid hormone receptor gene (c-erbA alpha) is expressed in advance of thyroid gland maturation during the early embryonic development of Xenopus laevis. Molecular and cellular biology 51 1656222
1989 Expression of the ErbA-beta class of thyroid hormone receptors is selectively lost in human colon carcinoma. The Journal of clinical investigation 50 2553781
2015 A Novel Mutation in THRA Gene Associated With an Atypical Phenotype of Resistance to Thyroid Hormone. The Journal of clinical endocrinology and metabolism 47 26037512
1991 Ontogeny of the v-erbA oncoprotein from the thyroid hormone receptor: an alteration in the DNA binding domain plays a role crucial for v-erbA function. Journal of virology 42 1672166
1984 Cellular homologs of the avian erythroblastosis virus erb-A and erb-B genes are syntenic in mouse but asyntenic in man. Proceedings of the National Academy of Sciences of the United States of America 42 6087351
2001 Suppression of the deafness and thyroid dysfunction in Thrb-null mice by an independent mutation in the Thra thyroid hormone receptor alpha gene. Human molecular genetics 40 11726557
1990 Expression of erbA alpha and beta mRNAs in regions of adult rat brain. Molecular and cellular endocrinology 40 2160381
1987 Nucleotide sequence of the chicken proto-oncogene c-erbA corresponding to domain 1 of v-erbA. European journal of biochemistry 40 3036525
1998 Identification and characterization of a novel corepressor interaction region in RVR and Rev-erbA alpha. Molecular endocrinology (Baltimore, Md.) 39 9482666
1994 Roles of v-erbA homodimers and heterodimers in mediating dominant negative activity by v-erbA. The Journal of biological chemistry 38 7904604
1993 NeP1. A ubiquitous transcription factor synergizes with v-ERBA in transcriptional silencing. Journal of molecular biology 38 8102652
1988 Genetic dissection of functional domains within the avian erythroblastosis virus v-erbA oncogene. Molecular and cellular biology 37 2847034
1999 The v-erbA oncogene (review). International journal of molecular medicine 35 10493974
1994 The erbA/thyroid hormone receptor genes in development of the central nervous system. Seminars in cancer biology 34 8061332
2019 Bisphenol A Alters Bmal1, Per2, and Rev-Erba mRNA and Requires Bmal1 to Increase Neuropeptide Y Expression in Hypothalamic Neurons. Endocrinology 33 30500912
1990 Sequence-specific DNA binding by the v-erbA oncogene protein of avian erythroblastosis virus. Journal of virology 33 1968105
1988 Triiodothyronine nuclear binding capacity in rat tissues correlates with a 6.0 kilobase (kb) and not a 2.6 kb messenger ribonucleic acid hybridization signal generated by a human c-erbA probe. Molecular endocrinology (Baltimore, Md.) 33 2460752
1987 The chicken c-erbA proto-oncogene is preferentially expressed in erythrocytic cells during late stages of differentiation. Molecular and cellular biology 33 3614196
1998 Leukemic transformation by the v-ErbA oncoprotein entails constitutive binding to and repression of an erythroid enhancer in vivo. The EMBO journal 32 9857194
1994 Unliganded c-erbA/thyroid hormone receptor induces trkB expression in neuroblastoma cells. Oncogene 31 8134111
1992 V-erbA and c-erbA proteins enhance transcriptional activation by c-jun. Oncogene 31 1349165
1988 Antipeptide antibodies recognize c-erbA and a related protein in human A431 carcinoma cells. Endocrinology 30 2904357
1990 Requirement for the C-terminal domain of the v-erbA oncogene protein for biological function and transcriptional repression. Oncogene 29 1969136
1990 A subpopulation of the avian erythroblastosis virus v-erbA protein, a member of the nuclear hormone receptor family, is glycosylated. Journal of virology 28 1967151
1997 Mechanism of transformation by v-ErbA: substitution for steroid hormone receptor function in self renewal induction. Oncogene 25 9264411
1994 Cloning of a thyroid hormone-responsive Rana catesbeiana c-erbA-beta gene. Developmental genetics 24 7923937
1990 The chicken c-erbA alpha-product induces expression of thyroid hormone-responsive genes in 3,5,3'-triiodothyronine receptor-deficient rat hepatoma cells. Molecular endocrinology (Baltimore, Md.) 24 2158623
2018 CRISPR/Cas9 Editing of the Mouse Thra Gene Produces Models with Variable Resistance to Thyroid Hormone. Thyroid : official journal of the American Thyroid Association 23 29205102
1993 Characterization of a functional promoter for the human thyroid hormone receptor alpha (c-erbA-1) gene. Oncogene 23 8455948
1994 Rat Rev-erbA alpha, an orphan receptor related to thyroid hormone receptor, binds to specific thyroid hormone response elements. Molecular endocrinology (Baltimore, Md.) 22 8015547
1992 The nuclear oncogenes v-erbA and v-ets cooperate in the induction of avian erythroleukemia. Oncogene 22 1347919
2019 New Case of Thyroid Hormone Resistance α Caused by a Mutation of THRA /TRα1. Journal of the Endocrine Society 21 30842990
2005 Cancer promoted by the oncoprotein v-ErbA may be due to subcellular mislocalization of nuclear receptors. Molecular endocrinology (Baltimore, Md.) 21 15650025
1994 c-ErbA, but not v-ErbA, competes with a putative erythroid repressor for binding to the carbonic anhydrase II promoter. Oncogene 21 7916146
1993 ErbA: tumor suppressor turned oncogene? FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 8102105
1993 Ontogeny of thyroid hormone receptors and c-erbA expression during brown adipose tissue development: evidence of fetal acquisition of the mature thyroid status. Endocrinology 21 8386604
1979 Construction and expression of a hybrid plasmid containing the Escherichia coli thrA and thrB genes. Molecular & general genetics : MGG 21 390305
2020 Two Novel Cases of Resistance to Thyroid Hormone Due to THRA Mutation. Thyroid : official journal of the American Thyroid Association 20 32204686