Affinage

TBXT

T-box transcription factor T · UniProt O15178

Round 2 corrected
Length
435 aa
Mass
47.4 kDa
Annotated
2026-04-28
130 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TBXT (brachyury) is a deeply conserved T-box transcription factor that serves as a master regulator of mesoderm specification, notochord differentiation, and axial elongation across chordates. It binds T-box DNA elements in target gene promoters primarily as a transcriptional activator, partnering context-dependently with SMAD1 during BMP4-driven mesoderm induction or with SMAD2/3 during activin-A-driven endoderm patterning, and directly represses CDKN1A (p21) to slow cell-cycle progression (PMID:26015544, PMID:22847733, PMID:23788039). TBXT expression is maintained by KDM6A/B-mediated H3K27 demethylation and participates in a positive FGFR/MEK/ERK feedback loop; germline duplication or common coding variants at the TBXT locus confer susceptibility to chordoma, while loss-of-function mutations cause congenital vertebral malformations (PMID:32855205, PMID:24445144, PMID:19801981, PMID:32672867). In hominoids, an Alu-element-mediated alternative splicing event produces an exon-skipped isoform whose relative abundance governs tail loss and modulates neural tube closure risk (PMID:38418917).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1995 Medium

    Cloning of amphioxus brachyury established that the gene is conserved across all three chordate subphyla and suggested that its ancestral role in notochord differentiation predates its functions in mesoderm formation.

    Evidence cDNA cloning, in situ hybridization, and phylogenetic analysis in amphioxus

    PMID:8575328

    Open questions at the time
    • Functional conservation inferred from expression only; no loss-of-function data in amphioxus
    • Regulatory elements driving notochord versus mesoderm expression not dissected
  2. 1996 High

    Cloning of the human T gene revealed near-complete identity of the T-box DNA-binding domain with mouse T and restricted expression to notochord-derived cells, establishing the molecular foundation for studying TBXT function in humans.

    Evidence cDNA cloning, genomic library screening, expression analysis, chromosomal mapping to 6q27

    PMID:8963900

    Open questions at the time
    • Downstream transcriptional targets in human cells unknown
    • No functional assay of human T protein activity
  3. 2001 Medium

    Synthesis of promoter-binding studies clarified that T-box proteins including brachyury achieve target gene specificity through sequence-specific recognition of T-box binding elements, with flanking nucleotide context governing individual factor selectivity.

    Evidence Review integrating gel-shift assays, reporter assays, and mutagenesis from multiple labs

    PMID:11148447

    Open questions at the time
    • Genome-wide binding landscape not yet mapped
    • No structural explanation for flanking-sequence discrimination
  4. 2009 High

    Identification of germline TBXT locus duplications in four multiplex chordoma families established copy-number gain of this single gene as a heritable susceptibility mechanism for familial chordoma, directly linking TBXT dosage to tumorigenesis.

    Evidence High-resolution array-CGH in familial chordoma kindreds and controls

    PMID:19801981

    Open questions at the time
    • Mechanism by which extra TBXT copies drive transformation not defined
    • Penetrance and modifier loci uncharacterized
  5. 2010 High

    Functional knockdown of TBXT in chordoma cells demonstrated that its expression is essential for chordoma proliferation, and genomic analyses revealed somatic copy-number gain in nearly half of sporadic chordomas, confirming TBXT as a bona fide oncogenic driver in this tumor type.

    Evidence FISH, qPCR, array-CGH, shRNA knockdown in U-CH1, xenograft validation

    PMID:21171078

    Open questions at the time
    • Direct transcriptional targets mediating the proliferative requirement not identified at this stage
    • Whether TBXT knockdown effect is cytostatic versus apoptotic not fully resolved
  6. 2011 High

    Epistasis experiments in human ESCs resolved a long-standing question about BMP4-induced cell fate by showing that TBXT is required for and precedes CDX2 expression during mesoderm specification, placing it upstream in the BMP4/FGF2-to-mesoderm differentiation cascade.

    Evidence shRNA knockdown in hESCs, gene expression analysis, epistasis with FGF/BMP signaling

    PMID:21816365

    Open questions at the time
    • Direct versus indirect regulation of CDX2 by TBXT not distinguished
    • Mechanism of FGF2 cooperation with BMP4 at the TBXT locus not resolved
  7. 2012 High

    ChIP-seq in chordoma cells revealed that TBXT acts predominantly as a transcriptional activator, directly binding 99 target genes through the conserved T-box motif and orchestrating an oncogenic network encompassing cell-cycle and extracellular matrix genes; concurrently, a GWAS identified a coding SNP (rs2305089) as a strong chordoma risk allele.

    Evidence ChIP-seq, shRNA knockdown, expression microarray in chordoma; GWAS with replication cohort

    PMID:22847733 PMID:23064415

    Open questions at the time
    • How the risk SNP alters TBXT protein function or expression not mechanistically resolved
    • Whether the 99 direct targets are universal or chordoma-specific unknown
  8. 2013 High

    Direct ChIP and reporter assays demonstrated that TBXT represses CDKN1A (p21) by binding a half T-box site in its promoter, thereby slowing cell-cycle progression and conferring resistance to chemotherapy and radiation—revealing a specific mechanism for TBXT-driven therapeutic resistance.

    Evidence ChIP, luciferase reporter assays, in vitro cytotoxicity, in vivo xenograft chemotherapy in lung carcinoma cells

    PMID:23788039

    Open questions at the time
    • Whether p21 repression is the sole or primary mediator of therapeutic resistance not established
    • Applicability of this mechanism to chordoma versus other TBXT-expressing tumors not tested
  9. 2014 High

    A positive feedback loop was delineated in which FGF2 activates FGFR/MEK/ERK to upregulate TBXT, and TBXT in turn maintains FGF2 secretion and pathway phosphorylation, promoting chordoma growth, survival, and EMT.

    Evidence Western blot, ELISA, selective kinase inhibitors, shRNA knockdown in chordoma cells

    PMID:24445144

    Open questions at the time
    • Whether TBXT directly transcribes FGF2 or acts indirectly not resolved
    • Contribution of other RTK pathways to the feedback loop not assessed
  10. 2015 High

    Genome-wide binding analysis in differentiating hESCs showed that TBXT occupies distinct chromatin landscapes depending on signaling context, physically interacting with SMAD1 in BMP4-induced mesoderm and with SMAD2/3 in activin-A-induced endoderm, establishing context-dependent cofactor usage as the basis for lineage-specific transcriptional programs.

    Evidence ChIP-seq, co-immunoprecipitation, BRA-level manipulation in hESCs

    PMID:26015544

    Open questions at the time
    • Structural basis for selective SMAD1 versus SMAD2/3 interaction unknown
    • Whether additional cofactors participate in each complex not addressed
  11. 2020 High

    Pharmacologic and genetic ablation of KDM6A/B demethylases increased H3K27me3 at the TBXT locus, silencing its expression and killing chordoma cells—an effect rescued by ectopic TBXT—thereby identifying KDM6A/B-mediated epigenetic maintenance as essential for TBXT transcription in chordoma, and a de novo TBXT missense mutation (R16L) in a congenital scoliosis patient was shown to impair DNA binding and act dominant-negatively, linking TBXT loss-of-function to vertebral malformation.

    Evidence KDM6A/B inhibitor + CRISPR KO + ChIP-seq + rescue overexpression in chordoma; WES + DNA-binding and reporter assays for R16L variant

    PMID:32672867 PMID:32855205

    Open questions at the time
    • Whether KDM6A versus KDM6B has non-redundant roles at the TBXT locus not fully resolved
    • R16L finding from a single patient; population-level confirmation of congenital scoliosis link pending
  12. 2024 High

    A hominoid-specific Alu-element insertion was shown to generate an exon-skipped TBXT isoform whose co-expression with full-length TBXT in transgenic mice phenocopied tail loss in a dose-dependent manner, directly explaining hominoid tail-loss evolution; expression of the exon-skipped isoform alone also caused neural tube defects, revealing a pleiotropic consequence of the same splicing event.

    Evidence Multiple transgenic mouse lines with controlled Tbxt isoform expression, genetic epistasis, embryological phenotyping

    PMID:38418917

    Open questions at the time
    • Molecular mechanism by which the truncated isoform interferes with full-length TBXT function not defined
    • Whether neural tube defect risk in humans is modulated by quantitative isoform balance remains untested
    • No structural data on the exon-skipped protein product

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for context-dependent SMAD cofactor selection, whether the exon-skipped isoform acts as a dominant-negative or has independent activity, and the full catalog of direct transcriptional targets during normal human embryogenesis versus oncogenesis.
  • No crystal structure of TBXT in complex with SMAD partners
  • Genome-wide target maps in normal human gastrulation tissue lacking
  • Therapeutic window for TBXT inhibition in chordoma versus developmental toxicity undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 5
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3
Partners
CDX2FGFR1KDM6AKDM6BSMAD1SMAD2SMAD3

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Brachyury (T) orthologs were cloned from amphioxus, demonstrating conservation of the gene across all three chordate subphyla. Spatial and temporal expression studies showed Brachyury transcripts distributed throughout the notochord anteroposterior axis and in presumptive mesoderm, supporting ancient roles in notochord differentiation predating roles in mesoderm formation. cDNA cloning, in situ hybridization, phylogenetic analysis Development (Cambridge, England) Medium 8575328
1996 The human T gene was cloned and characterized: it encodes a transcription factor with 91% overall amino acid identity to mouse T protein and 100% identity across the 77-amino-acid T-box DNA-binding domain. Human T expression is confined to notochord-derived cells, and the gene maps to chromosome 6q27. cDNA cloning, genomic library screening, expression analysis, chromosomal mapping Genome research High 8963900
2001 T-box proteins including Brachyury regulate downstream effector genes by binding T-box binding elements (T-sites) in target gene promoters; the specificity of individual T-box factors is determined by the precise sequence of the T-site and flanking nucleotides, enabling distinct transcriptional programs. Review integrating reporter assays, gel-shift assays, and mutagenesis from multiple studies Development, growth & differentiation Medium 11148447
2006 Brachyury (T) protein was localized by immunohistochemistry to the primitive streak, nascent embryonic mesoderm, node, notochord, notochord-associated endoderm, posterior neurectoderm, and allantois midline during mouse gastrulation. Novel sites including the developing heart, visceral endoderm, extraembryonic ectoderm, and chorionic ectoderm were also identified, demonstrating broader spatiotemporal activity than previously appreciated. Sectional immunohistochemistry in mouse conceptus across gastrulation stages Gene expression patterns : GEP Medium 16545989
2009 Germline duplication of the T (brachyury) gene locus on chromosome 6q27 was identified in four multiplex chordoma families with at least three affected members each. The duplicated region contained only the T gene, establishing T gene copy-number gain as a susceptibility mechanism for familial chordoma. High-resolution array-CGH on familial chordoma cases and controls Nature genetics High 19801981
2010 Chromosomal aberrations resulting in copy-number gain of the T locus are common in sporadic chordomas (~46% of cases including polysomy and amplification). Knockdown of T in chordoma cell line U-CH1 caused marked decrease in cell proliferation and morphological features of senescence, demonstrating that brachyury expression is critical for chordoma cell proliferation in vitro. FISH, qPCR, array-CGH, shRNA knockdown, xenograft validation in NOD/SCID mice The Journal of pathology High 21171078
2011 BMP4 cooperates with FGF2/ERK signaling to induce mesoderm differentiation from human and mouse pluripotent stem cells via BRACHYURY (BRA). BRA was necessary for and preceded CDX2 expression; both genes were required for mesodermal and trophoblast-associated gene expression, establishing BRA as a key mediator of BMP-induced mesoderm specification rather than trophoblast lineage commitment. shRNA knockdown in hESCs, gene expression analysis, epistasis experiments with FGF/BMP signaling Cell stem cell High 21816365
2012 Using shRNA-mediated knockdown, ChIP-seq, and gene expression microarray in a chordoma cell line, brachyury was shown to act primarily as a transcriptional activator, binding 99 direct target genes via the T-box binding motif (identical to that in mouse, Xenopus, and zebrafish). Brachyury was identified as a master regulator of an oncogenic transcriptional network encompassing cell cycle components and extracellular matrix genes. shRNA knockdown, ChIP-seq, gene expression microarray, bioinformatics, validation in human chordoma samples The Journal of pathology High 22847733
2012 A common nonsynonymous SNP in the T gene (rs2305089) was strongly associated with chordoma risk (OR=6.1, P=4.4×10⁻⁹) in a genome-wide association study replicated in an independent cohort, implicating variation in TBXT itself as a direct genetic risk factor for chordoma. GWAS with whole-exome and Sanger sequencing, replication cohort Nature genetics High 23064415
2013 Brachyury expression in human lung carcinoma cells correlates with resistance to chemotherapy and radiation. Chromatin immunoprecipitation and luciferase reporter assays demonstrated that Brachyury directly binds a half T-box consensus site in the CDKN1A (p21) gene promoter, repressing its expression, downregulating cyclin D1 and phosphorylated Rb, and thereby slowing cell cycle progression to confer therapeutic resistance. ChIP, luciferase reporter assays, in vitro cytotoxicity, in vivo xenograft chemotherapy experiments Cell death & disease High 23788039
2014 In chordoma cell lines, FGF2 activates the FGFR/MEK/ERK signaling cascade, which phosphorylates FRS2-α and promotes nuclear translocation of phospho-ERK, resulting in increased brachyury expression. Brachyury in turn maintains FGF2 secretion and FGFR/MEK/ERK phosphorylation, forming a positive feedback loop that promotes cell growth, survival, and epithelial-mesenchymal transition. Knockdown of brachyury disrupted this loop and induced apoptosis. Western blot, ELISA, immunofluorescence, selective kinase inhibitors, shRNA knockdown of brachyury Carcinogenesis High 24445144
2015 Genome-wide ChIP-seq in differentiating hESCs revealed that Brachyury (BRA) has distinct binding landscapes in BMP4-induced mesoderm versus activin-A-induced endoderm progenitors. BRA physically interacts and collaborates with SMAD1 (in mesoderm) or SMAD2/3 (in endoderm) to regulate cell-specific target gene expression. Manipulation of BRA levels showed it is essential for mesoderm but not endoderm formation. ChIP-seq, co-immunoprecipitation, gene expression analysis, BRA level manipulation in hESCs Development (Cambridge, England) High 26015544
2017 Somatic duplications of the brachyury (T) locus were identified in up to 27% of sporadic chordoma cases, with rearrangement architecture recapitulating the pathogenic germline duplications of familial chordoma. PI3K signaling mutations were found in 16% of cases, and LYST was recurrently inactivated in 10%. Whole-genome sequencing, copy-number analysis of 104 sporadic chordoma cases Nature communications High 29026114
2019 Two linked TBXT variants (missense c.334G>T causing p.Gly112Trp in the T-box domain, plus synonymous c.333G>C) were associated with the tailless phenotype in fat-rumped sheep. Crossbreeding showed the CT/CT genotype (recessive) causes tail shortening, indicating the Gly112Trp substitution in the T-box DNA-binding domain impairs TBXT function in tail development. Direct sequencing of exon 2 in 301 individuals from 13 breeds, genotyping of 380 samples, crossbreeding experiments Animal genetics Medium 31475743
2020 Pharmacologic inhibition of H3K27 demethylases KDM6A (UTX) and KDM6B (JMJD3) with compound KDOBA67 caused genome-wide increase in repressive H3K27me3 at the TBXT locus with concomitant reduction of active marks (H3K27ac, H3K9ac, H3K4me3), leading to reduced TBXT protein levels and chordoma cell death. Ectopic overexpression of TBXT rescued viability, demonstrating that TBXT is a direct target of KDM6A/B-dependent epigenetic regulation and is required for chordoma cell survival. Pharmacologic KDM6A/B inhibition, CRISPR/Cas9 dual KO of KDM6A/B, ChIP-seq (H3K27me3, H3K27ac, H3K4me3), TBXT overexpression rescue, primary patient-derived cultures Cancer research High 32855205
2020 A de novo missense mutation in TBXT (c.G47T; p.R16L) was identified by whole-exome sequencing in a congenital scoliosis patient. The R16L substitution compromised TBXT binding to its target DNA sequence, reduced transcriptional activity, and exhibited a dominant-negative effect on wild-type TBXT, establishing that TBXT transcriptional activity in the T-box domain is required for normal vertebral development. Whole-exome sequencing, DNA-binding assay, transcriptional activity reporter assay, dominant-negative functional analysis Journal of orthopaedic research Medium 32672867
2024 A hominoid-specific Alu element insertion in an intron of TBXT pairs with an ancestral reverse-oriented Alu element to produce an alternative splicing event that skips an exon. Mouse models co-expressing full-length and exon-skipped Tbxt isoforms (mimicking hominoid TBXT expression) displayed complete tail loss or shortened tails depending on relative isoform abundance in the embryonic tail bud. Mice expressing only the exon-skipped isoform also developed neural tube defects, linking TBXT alternative splicing to both tail-loss evolution and neural tube defect risk. Transgenic mouse models with controlled Tbxt isoform expression, genetic epistasis, embryological phenotyping Nature High 38418917

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 T-cell antigen receptor genes and T-cell recognition. Nature 2938 3043226
2009 T cell activation. Annual review of immunology 1555 19132916
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
2009 A census of human transcription factors: function, expression and evolution. Nature reviews. Genetics 1191 19274049
2001 T cell anergy. Annual review of immunology 1030 12471050
2017 Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science (New York, N.Y.) 934 28473536
1990 Stimulation of p21ras upon T-cell activation. Nature 885 2201921
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2015 G&T-seq: parallel sequencing of single-cell genomes and transcriptomes. Nature methods 571 25915121
1997 Homotypic vacuolar fusion mediated by t- and v-SNAREs. Nature 390 9144293
2021 An NK-like CAR T cell transition in CAR T cell dysfunction. Cell 314 34861191
2011 BRACHYURY and CDX2 mediate BMP-induced differentiation of human and mouse pluripotent stem cells into embryonic and extraembryonic lineages. Cell stem cell 304 21816365
2006 Cytotoxic T cells. The Journal of investigative dermatology 299 16417215
2008 Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification. Cell stem cell 290 18593560
2014 Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proceedings of the National Academy of Sciences of the United States of America 264 24958858
1996 Mechanism of telomerase induction during T cell activation. Experimental cell research 258 8892971
2002 Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10. Blood 253 11781247
2003 The DNA sequence and analysis of human chromosome 6. Nature 242 14574404
2024 T Cell Exhaustion. Annual review of immunology 237 38166256
2009 T (brachyury) gene duplication confers major susceptibility to familial chordoma. Nature genetics 231 19801981
2012 Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS genetics 222 22589738
2005 How T cells 'see' antigen. Nature immunology 201 15716973
2011 Mechanisms of necroptosis in T cells. The Journal of experimental medicine 197 21402742
1986 A common mechanism of chromosomal translocation in T- and B-cell neoplasia. Science (New York, N.Y.) 189 3490692
2008 Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue. The American journal of surgical pathology 182 18301055
2007 Human TBX1 missense mutations cause gain of function resulting in the same phenotype as 22q11.2 deletions. American journal of human genetics 165 17273972
1995 Conservation of Brachyury (T) genes in amphioxus and vertebrates: developmental and evolutionary implications. Development (Cambridge, England) 165 8575328
2010 Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study. The Journal of pathology 158 21171078
1992 Costimulation of T-cell growth. Current opinion in immunology 155 1418704
2010 T regulatory cells maintain intestinal homeostasis by suppressing γδ T cells. Immunity 151 21074460
2016 Mutant KRAS Conversion of Conventional T Cells into Regulatory T Cells. Cancer immunology research 141 26880715
2002 The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor gene p14ARF via a variant T-site in the initiator. The Journal of biological chemistry 135 12000749
2008 Brachyury, SOX-9, and podoplanin, new markers in the skull base chordoma vs chondrosarcoma differential: a tissue microarray-based comparative analysis. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 129 18820665
2016 Separation and parallel sequencing of the genomes and transcriptomes of single cells using G&T-seq. Nature protocols 126 27685099
2022 Human transcription factor protein interaction networks. Nature communications 123 35140242
2015 Brachyury and SMAD signalling collaboratively orchestrate distinct mesoderm and endoderm gene regulatory networks in differentiating human embryonic stem cells. Development (Cambridge, England) 123 26015544
2017 The driver landscape of sporadic chordoma. Nature communications 122 29026114
2012 Brachyury, a driver of the epithelial-mesenchymal transition, is overexpressed in human lung tumors: an opportunity for novel interventions against lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 107 22611028
2009 Activating systemic autoimmunity: B's, T's, and tolls. Current opinion in immunology 106 19800208
2003 T-bet regulates T-independent IgG2a class switching. International immunology 106 12882831
2015 Nuclear Brachyury Expression Is Consistent in Chordoma, Common in Germ Cell Tumors and Small Cell Carcinomas, and Rare in Other Carcinomas and Sarcomas: An Immunohistochemical Study of 5229 Cases. The American journal of surgical pathology 105 26099010
2021 Base-edited CAR T cells for combinational therapy against T cell malignancies. Leukemia 104 34035409
2001 T-targets: clues to understanding the functions of T-box proteins. Development, growth & differentiation 100 11148447
2012 A common single-nucleotide variant in T is strongly associated with chordoma. Nature genetics 99 23064415
1986 A new translocation, t(10;14)(q24;q11), in T cell neoplasia. Blood 99 3485458
2001 Upregulation of CD4 on CD8+ T cells: CD4dimCD8bright T cells constitute an activated phenotype of CD8+ T cells. Immunology 94 11454056
2010 Regulatory T cells interfere with glutathione metabolism in dendritic cells and T cells. The Journal of biological chemistry 92 21037289
1999 CD47 signals T cell death. Journal of immunology (Baltimore, Md. : 1950) 92 10358145
2008 The T-body approach: redirecting T cells with antibody specificity. Handbook of experimental pharmacology 90 18071952
2010 Revisiting chordoma with brachyury, a "new age" marker: analysis of a validation study on 51 cases. Archives of pathology & laboratory medicine 82 20670140
2001 Morphine directs T cells toward T(H2) differentiation. Surgery 82 11490364
2006 Why photoreceptors die (and why they don't). BioEssays : news and reviews in molecular, cellular and developmental biology 81 16547945
2004 Notch signaling in T- and B-cell development. Current opinion in immunology 78 15023410
1999 Analysis of select folate pathway genes, PAX3, and human T in a Midwestern neural tube defect population. Teratology 78 10332959
2018 Transient T-bet expression functionally specifies a distinct T follicular helper subset. The Journal of experimental medicine 75 30232200
2017 STAT5BN642H is a driver mutation for T cell neoplasia. The Journal of clinical investigation 75 29200404
2012 An integrated functional genomics approach identifies the regulatory network directed by brachyury (T) in chordoma. The Journal of pathology 75 22847733
1992 Endowing T cells with antibody specificity using chimeric T cell receptors. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 74 1464371
2024 On the genetic basis of tail-loss evolution in humans and apes. Nature 72 38418917
2004 TCR trafficking in resting and stimulated T cells. Critical reviews in immunology 72 14995914
2014 CD3bright signals on γδ T cells identify IL-17A-producing Vγ6Vδ1+ T cells. Immunology and cell biology 69 25385067
2014 The FGFR/MEK/ERK/brachyury pathway is critical for chordoma cell growth and survival. Carcinogenesis 67 24445144
2014 T-box transcription factor brachyury is associated with prostate cancer progression and aggressiveness. Clinical cancer research : an official journal of the American Association for Cancer Research 67 25009296
2013 The embryonic transcription factor Brachyury blocks cell cycle progression and mediates tumor resistance to conventional antitumor therapies. Cell death & disease 67 23788039
2012 Genome-wide association identifies the T gene as a novel asthma pharmacogenetic locus. American journal of respiratory and critical care medicine 67 22538805
2011 Brachyury expression predicts poor prognosis at early stages of colorectal cancer. European journal of cancer (Oxford, England : 1990) 67 21220197
1996 The human homolog T of the mouse T(Brachyury) gene; gene structure, cDNA sequence, and assignment to chromosome 6q27. Genome research 67 8963900
2010 Molecular mechanisms by which T-bet regulates T-helper cell commitment. Immunological reviews 64 20969596
2006 A genomic analysis of adult T-cell leukemia. Oncogene 63 16909099
2007 Sympatric occurrence of Taenia solium, T. saginata, and T. asiatica, Thailand. Emerging infectious diseases 60 18252126
2014 How steroids steer T cells. Cell reports 59 24856295
2006 Localization of Brachyury (T) in embryonic and extraembryonic tissues during mouse gastrulation. Gene expression patterns : GEP 58 16545989
2000 Costimulation of T cells. American journal of respiratory and critical care medicine 57 11029388
2023 Characteristics of premanufacture CD8+T cells determine CAR-T efficacy in patients with diffuse large B-cell lymphoma. Signal transduction and targeted therapy 56 37875502
1980 Evidence for unequal crossing over within the mouse T/t complex. Proceedings of the National Academy of Sciences of the United States of America 55 6934533
2002 Expression regulation of the endochitinase chit36 from Trichoderma asperellum (T. harzianum T-203). Current genetics 54 12478390
1997 Mechanisms of transcriptional regulation of cellular genes by SV40 large T- and small T-antigens. Virus genes 54 9421878
2020 The Physiopathology of T- Cell Acute Lymphoblastic Leukemia: Focus on Molecular Aspects. Frontiers in oncology 53 32185137
2008 Intracellular signals of T cell costimulation. Cellular & molecular immunology 53 18761811
1997 T cell signalling through CD73. Cellular signalling 52 9113412
2015 T- and B-cell subsets in periodontitis. Periodontology 2000 51 26252409
2006 Depletion of alloreactive T cells via CD69: implications on antiviral, antileukemic and immunoregulatory T lymphocytes. Bone marrow transplantation 51 16327814
2021 T Cell Exhaustion and CAR-T Immunotherapy in Hematological Malignancies. BioMed research international 50 33728333
2009 Is there a difference between T- and B-lymphocyte morphology? Journal of biomedical optics 49 20059274
2015 T cells, teeth and tissue destruction - what do T cells do in periodontal disease? Molecular oral microbiology 48 26505640
2002 Ceramide: does it matter for T cells? Trends in immunology 48 11801441
2016 T Cells Going Innate. Trends in immunology 47 27402226
2025 T cell malignancies after CAR T cell therapy in the DESCAR-T registry. Nature medicine 46 39779930
2023 Effects of lactate on metabolism and differentiation of CD4+T cells. Molecular immunology 46 36621062
2014 The emergence of T-bodies/CAR T cells. Cancer journal (Sudbury, Mass.) 43 24667957
1995 T-cell activation. Two for T. Current biology : CB 43 7583143
2018 SATB1 in Malignant T Cells. The Journal of investigative dermatology 41 29751003
2013 Functional T cell immunodeficiencies (with T cells present). Annual review of immunology 41 23298211
2003 T lymphocytes. The international journal of biochemistry & cell biology 41 12672468
2020 Inhibition of Histone H3K27 Demethylases Inactivates Brachyury (TBXT) and Promotes Chordoma Cell Death. Cancer research 39 32855205
2016 Life and cancer without telomerase: ALT and other strategies for making sure ends (don't) meet. Critical reviews in biochemistry and molecular biology 37 27892716
2010 T-bet-mediated differentiation of the activated CD8+ T cell. European journal of immunology 37 21182077
2005 The yins of T cell activation. Science's STKE : signal transduction knowledge environment 36 15632417
2002 Induction of T --> G and T --> A transversions by 5-formyluracil in mammalian cells. Mutation research 36 11719107
1993 T-cell receptors are expressed but down-regulated on intradecidual T lymphocytes. American journal of reproductive immunology (New York, N.Y. : 1989) 36 8503990
2017 Detection of the circulating tumor DNAs in angioimmunoblastic T- cell lymphoma. Annals of hematology 35 28634614
2022 T Cell Recognition of Tumor Neoantigens and Insights Into T Cell Immunotherapy. Frontiers in immunology 33 35222422
2012 Typhoid fever: "you can't hit what you can't see". Gut microbes 33 22156762
1998 Requirement for Jak3 in mature T cells: its role in regulation of T cell homeostasis. Journal of immunology (Baltimore, Md. : 1950) 32 9498750
1992 T helper cells. Current opinion in immunology 32 1418713
2022 Engineered T Cells: CAR T Cell Therapy and Beyond. Current oncology reports 31 35059997
2020 DP1 Activation Reverses Age-Related Hypertension Via NEDD4L-Mediated T-Bet Degradation in T Cells. Circulation 30 31893939
1994 Localization of clonal T cells to the epidermis in cutaneous T-cell lymphoma. Journal of the American Academy of Dermatology 29 7929915
2021 Exploiting T cell signaling to optimize engineered T cell therapies. Trends in cancer 28 34810156
2022 Donor T cells for CAR T cell therapy. Biomarker research 27 35365224
2016 Loss of Functionally Redundant p38 Isoforms in T Cells Enhances Regulatory T Cell Induction. The Journal of biological chemistry 27 28011639
2010 Critical requirement of GABPalpha for normal T cell development. The Journal of biological chemistry 27 20139079
2021 For whom the T cells troll? Bispecific T-cell engagers in glioblastoma. Journal for immunotherapy of cancer 26 34795007
2009 Learning our L.I.M.I.T.S.: less is more in teaching science. Advances in physiology education 25 19261755
2019 Two linked TBXT (brachyury) gene polymorphisms are associated with the tailless phenotype in fat-rumped sheep. Animal genetics 24 31475743
2019 T-cells "à la CAR-T(e)" - Genetically engineering T-cell response against cancer. Advanced drug delivery reviews 23 30653988
1982 Expression of glucagon receptors on T- and B- lymphoblasts: comparison with insulin receptors. Endocrinology 23 6284489
2023 CAR T cell therapy becomes CHIC: "cytokine help intensified CAR" T cells. Frontiers in immunology 22 36700225
1978 T- and B-cell distribution in pregnancy. JAMA 22 306448
2010 γδ T lymphocytes kill T regulatory cells through CD1d. Immunology 21 21050191
2021 MicroRNA Regulation of T-Cell Exhaustion in Cutaneous T Cell Lymphoma. The Journal of investigative dermatology 20 34774537
2000 T-cell immunodeficiencies. Pediatric clinics of North America 20 11130995
2010 Hepatocellular carcinoma with immature T-cell (T-lymphoblastic) proliferation. Journal of Korean medical science 18 20119589
1995 Regulation and function of p21ras in T lymphocytes. Cancer surveys 18 7720060
2020 Genetic variants of TBX6 and TBXT identified in patients with congenital scoliosis in Southern China. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 17 32672867
2017 Genetic alterations affecting GTPases and T-cell receptor signaling in peripheral T-cell lymphomas. Small GTPases 17 27898263
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