Affinage

CASP4

Caspase-4 · UniProt P49662

Round 2 corrected
Length
377 aa
Mass
43.3 kDa
Annotated
2026-04-28
130 papers in source corpus 15 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Caspase-4 is an inflammatory cysteine protease that functions as an intracellular receptor for cytosolic lipopolysaccharide (LPS), directly binding LPS via its CARD domain to undergo oligomerization, autoprocessing, and activation, thereby driving pyroptotic cell death through cleavage of gasdermin D (GSDMD) (PMID:25119034, PMID:26375003, PMID:32109412). Caspase-4-dependent pyroptosis triggers secondary activation of the NLRP3 inflammasome for IL-1β maturation and independently mediates IL-1α release in human macrophages and epithelial cells during gram-negative bacterial infection (PMID:26174085, PMID:25964352, PMID:25121752). GBP1 serves as an upstream LPS sensor that recruits caspase-4 to cytosolic bacterial surfaces, assembling the platform required for noncanonical inflammasome activation (PMID:32581219). Caspase-4 also localizes to the endoplasmic reticulum membrane and functions as an ER stress-activated caspase that promotes apoptosis independently of mitochondrial Bcl-2 pathways (PMID:15123740).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1995 High

    Establishing caspase-4 as a distinct ICE-family protease resolved whether additional ICE-like enzymes existed and showed that, despite structural similarity to caspase-1, caspase-4 cannot process pro-IL-1β and instead has pro-apoptotic activity.

    Evidence cDNA cloning, in vitro cleavage assays, and COS/fibroblast transfection showing self-processing and apoptosis induction

    PMID:7743998 PMID:7797592

    Open questions at the time
    • Physiological substrates of caspase-4 were unknown
    • Upstream signals triggering caspase-4 activation in vivo were not identified
    • Relationship to other apoptotic caspase cascades was not defined
  2. 1996 Medium

    Placement of caspase-4 downstream of caspase-8 in the Fas signaling cascade addressed how caspase-4 is activated during receptor-mediated apoptosis, suggesting it participates as a downstream effector.

    Evidence In vitro processing of TX/CASP4 by recombinant caspase-8 (Mch5)

    PMID:8962078

    Open questions at the time
    • Single in vitro study without cellular validation of the caspase-8→caspase-4 cascade
    • Whether caspase-4 is a physiologically relevant Fas-pathway effector was not tested in loss-of-function experiments
  3. 2004 High

    Localization of caspase-4 to the ER membrane and its specific activation by ER stress — not blocked by Bcl-2 — revealed a previously unknown mitochondria-independent apoptotic pathway and linked caspase-4 to amyloid-β-induced cell death.

    Evidence Subcellular fractionation, ER stress reagent treatment, Bcl-2 epistasis, siRNA knockdown reducing ER stress- and Aβ-induced apoptosis

    PMID:15123740

    Open questions at the time
    • Direct ER-stress substrates of caspase-4 were not identified
    • Whether caspase-4 ER function is relevant in vivo (e.g., in neurodegeneration) was not demonstrated
    • The mechanism linking ER stress to caspase-4 cleavage/activation remained undefined
  4. 2014 High

    The landmark discovery that caspase-4 directly binds LPS via its CARD domain, oligomerizes, and triggers pyroptosis established it as a bona fide intracellular innate immune receptor — fundamentally redefining its biology from an apoptotic caspase to a pattern-recognition receptor.

    Evidence Purified caspase-4 LPS-binding assays, oligomerization upon LPS addition, CARD mutagenesis ablating binding and pyroptosis, LPS electroporation and bacterial infection in cells

    PMID:25119034

    Open questions at the time
    • The downstream effector substrate of caspase-4-mediated pyroptosis was unknown
    • How caspase-4 encounters cytosolic LPS during infection was not resolved
    • Structural basis of CARD–LPS interaction was not determined
  5. 2014 High

    Demonstration that caspase-4 drives pyroptotic extrusion of infected epithelial cells and IL-18 activation established its role in mucosal barrier defense against enteric pathogens.

    Evidence siRNA depletion of caspase-4 in polarized intestinal epithelial monolayers infected with Salmonella, measuring pyroptosis, IL-18, and bacterial colonization

    PMID:25121752

    Open questions at the time
    • Relative contributions of caspase-4 versus caspase-5 in intestinal epithelium were not fully resolved
    • In vivo human relevance relies on extrapolation from mouse caspase-11 knockout data
  6. 2015 High

    Identification of GSDMD as the essential pyroptosis-executing substrate of caspase-4 resolved the long-standing question of how inflammatory caspase activation leads to cell lysis, revealing that caspase-4 cleaves the GSDMD interdomain linker to release the pore-forming N-terminal domain.

    Evidence Genome-wide CRISPR screen in macrophages, GSDMD KO validation, in vitro cleavage by caspase-1/4/5/11, domain mapping

    PMID:26375003

    Open questions at the time
    • Structural basis for how caspase-4 recognizes GSDMD was not yet determined
    • Whether GSDMD is the sole pyroptotic effector downstream of caspase-4 was not excluded
  7. 2015 High

    Genetic studies in human monocytic cells clarified the division of labor: caspase-4-dependent pyroptosis is sufficient for cell death and secondarily activates NLRP3/caspase-1 for IL-1β maturation, while caspase-4 independently governs IL-1α release in primary macrophages.

    Evidence CRISPR knockout of caspase-4/5 in THP1 cells, primary macrophage knockdown, LPS transfection, Salmonella infection, NLRP3 inhibitor MCC950, IL-1α/IL-1β ELISA

    PMID:25964352 PMID:26173988 PMID:26174085 PMID:26508369

    Open questions at the time
    • Precise mechanism by which caspase-4-induced pyroptosis triggers NLRP3 (beyond potassium efflux) remained incompletely defined
    • Functional redundancy between caspase-4 and caspase-5 in different human cell types was not fully resolved
  8. 2020 High

    Crystal structures of the autoprocessed caspase-4–GSDMD-C complex revealed that autoprocessing generates a unique β-sheet interface in the p10 subunit that binds the GSDMD-C domain, explaining how caspase-4 recognizes GSDMD independently of canonical tetrapeptide motifs.

    Evidence X-ray crystallography of caspase-4/11–GSDMD-C complexes, site-directed mutagenesis, in vitro cleavage and binding assays

    PMID:32109412

    Open questions at the time
    • Full-length caspase-4–GSDMD complex structure (including GSDMD-N release) was not captured
    • How LPS-bound oligomeric caspase-4 transitions to GSDMD cleavage in a cellular context was not structurally resolved
  9. 2020 High

    Identification of GBP1 as the upstream cytosolic LPS sensor that assembles a GBP coat on bacteria and recruits caspase-4 resolved how caspase-4 accesses LPS on intact bacterial surfaces during infection.

    Evidence GBP knockout cell lines, confocal imaging of GBP/caspase-4 colocalization on cytosolic Salmonella, LPS-binding assay with purified GBP1

    PMID:32581219

    Open questions at the time
    • Whether GBP1-dependent recruitment is required in all cell types or only epithelial cells was not determined
    • The precise molecular interface between the GBP coat and the caspase-4 CARD is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the CARD–LPS interaction, how GBP-dependent caspase-4 recruitment is coordinated with oligomerization and autoprocessing in vivo, and whether the ER-stress and innate-immune functions of caspase-4 represent distinct or interconnected pathways.
  • No structure of the CARD–LPS complex exists
  • In vivo relevance of the ER-stress function versus the LPS-sensing function in human disease is unresolved
  • Functional redundancy with caspase-5 in different tissue contexts is incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0140299 molecular sensor activity 2
Localization
GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-5357801 Programmed Cell Death 5
Partners
CASP8GBP1GSDMDNLRP3

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 CASP4 (originally named TX or ICErelII/ICH-2) was identified as a novel cysteine protease with >50% sequence identity to ICE (caspase-1), capable of self-cleavage and cleavage of the p30 ICE precursor but not of pro-IL-1β; overexpression induced apoptosis in COS cells, establishing CASP4 as a pro-apoptotic member of the ICE/CED-3 family. cDNA cloning, transfection of COS cells, in vitro protease cleavage assays, computer homology modeling The EMBO journal High 7743998 7797592
1995 ICErelII (CASP4) and ICErelIII (CASP5), cloned from human monocytic cells, share the conserved catalytic pentapeptide QACRG with ICE; truncated (pro-domain-less) forms of ICErelII effectively induce fibroblast apoptosis; neither ICErelII nor ICErelIII processes pro-IL-1β, indicating substrate specificity distinct from caspase-1. cDNA cloning from human monocytes, transfection of fibroblasts, in vitro protease assay with pro-IL-1β substrate The Journal of biological chemistry High 7797592
1996 Recombinant Mch5 (caspase-8) can process and activate CASP4 (referred to as TX in the cascade), placing CASP4 downstream of Mch5 in the Fas apoptotic protease cascade; CASP4 is identified as one of the ICE-like proteases activated by the upstream initiator caspase. Bacterial expression of recombinant Mch5, in vitro processing assays with ICE-like caspase substrates including TX/CASP4 Proceedings of the National Academy of Sciences of the United States of America Medium 8962078
1998 Apaf-1 associates with caspase-4 (among other death proteases) in mammalian cells, as shown by co-immunoprecipitation; however, the functional activation of caspase-9 by Apaf-1 is the primary pathway, and Bcl-XL inhibits Apaf-1-dependent caspase processing. Co-immunoprecipitation in mammalian cells, recombinant Bcl-XL inhibition assay Proceedings of the National Academy of Sciences of the United States of America Medium 9539746
2002 Caspase-4 cleaves IL-1F7b (IL-1H4) at a caspase recognition site, albeit less efficiently than caspase-1, generating mature IL-1F7b; other caspases and Granzyme-B did not cleave IL-1F7b, identifying IL-1F7b as a substrate for both caspase-1 and caspase-4. In vitro cleavage assay with purified caspases and recombinant IL-1F7b substrate Cytokine Medium 12096920
2004 Human caspase-4 localizes to the endoplasmic reticulum (ER) membrane and is specifically cleaved/activated in response to ER stress-inducing reagents but not by other apoptotic stimuli; this cleavage is not blocked by Bcl-2 overexpression, indicating a mitochondria-independent pathway. siRNA knockdown of caspase-4 reduces ER stress-induced apoptosis. Caspase-4 is also cleaved by amyloid-beta (Aβ), and Aβ-induced apoptosis is reduced by caspase-4 siRNA, suggesting a role in Alzheimer's disease pathogenesis. Subcellular fractionation/localization, western blot of caspase-4 cleavage upon ER stress, Bcl-2 overexpression epistasis, siRNA knockdown with cell death quantification, Aβ treatment assays The Journal of cell biology High 15123740
2014 Human caspase-4 (and mouse caspase-11) directly bind LPS and lipid A with high specificity and affinity via their CARD domain; LPS binding induces caspase-4/11 oligomerization and activation, triggering pyroptosis. CARD-domain point mutants that cannot bind LPS fail to oligomerize, activate, or induce pyroptosis upon LPS electroporation or bacterial infection, establishing caspase-4 as an intracellular LPS pattern recognition receptor. Insect-cell purification of caspase-4/11, LPS-binding assay, oligomerization assay upon LPS addition, CARD-domain point mutagenesis, electroporation of LPS into cells, bacterial infection assays Nature High 25119034
2014 In polarized intestinal epithelial cells, caspase-4 (human ortholog of murine caspase-11) mediates noncanonical inflammasome activation in response to intracellular LPS from Salmonella Typhimurium and extracellular enteric pathogens, driving pyroptotic cell death that extrudes infected cells from the epithelium and governing IL-18 activation; siRNA depletion of caspase-4 increased bacterial colonization. siRNA depletion of caspase-4 in polarized epithelial monolayers, bacterial colonization assay, pyroptosis/cell death quantification, IL-18 measurement, caspase-11 KO mouse intestinal colonization model Cell host & microbe High 25121752
2015 Gasdermin D (GSDMD) was identified as the essential pyroptosis executioner cleaved by caspase-4 (and caspase-1/5/11); caspase-4/5/11 specifically cleave the linker between the gasdermin-N and gasdermin-C domains of GSDMD, releasing the intramolecularly inhibited gasdermin-N domain which has intrinsic pyroptosis-inducing activity; GSDMD-deficient cells resist pyroptosis induced by cytosolic LPS. Genome-wide CRISPR-Cas9 screen in mouse macrophages, GSDMD knockout cell validation, in vitro cleavage assay of GSDMD by caspase-1/4/5/11, domain mapping of cleavage site Nature High 26375003
2015 Caspase-4 (but not caspase-5 alone) is the primary mediator of pyroptotic cell death and IL-1β production in human monocytic THP1 cells in response to cytosolic LPS delivered by transfection or Salmonella infection; caspase-4-dependent pyroptosis drives NLRP3 inflammasome activation (requiring potassium efflux, NLRP3, ASC, and caspase-1) for IL-1β maturation, while caspase-4 activation alone is sufficient for pyroptosis. Genetic deletion of caspase-4 and caspase-5 (individually and together) in THP1 cells, LPS transfection, Salmonella infection, IL-1β ELISA, cell death assay, NLRP3 inhibitor (MCC950) treatment European journal of immunology High 26173988 26174085
2015 In primary human macrophages infected with gram-negative bacteria, caspase-4 mediates IL-1α release and cell death via the noncanonical inflammasome, independently of caspase-1; caspase-1 is required for IL-1β secretion, while caspase-4 specifically governs IL-1α release and pyroptotic death in response to bacteria that introduce LPS into the cytosol via specialized secretion systems. Primary human macrophage infection assays with diverse gram-negative pathogens, caspase-1 and caspase-4 inhibition/knockdown, IL-1α and IL-1β ELISA, cell death assay Proceedings of the National Academy of Sciences of the United States of America High 25964352
2015 In human monocytes, caspase-4 and caspase-5 mediate IL-1α and IL-1β release upon LPS stimulation through a one-step noncanonical inflammasome pathway; caspase-5 (but not caspase-4) undergoes rapid processing upon LPS treatment; this pathway requires Syk kinase activity and Ca²⁺ flux initiated by CD14/TLR4-mediated LPS internalization. siRNA knockdown of caspase-4 and caspase-5 in primary human monocytes, LPS stimulation, IL-1 ELISA, western blot for caspase cleavage, pharmacological inhibition of Syk and Ca²⁺ flux Nature communications High 26508369
2020 Site-specific autoprocessing of caspase-4 (and caspase-11), generating a p10 product, is required and sufficient for GSDMD cleavage and pyroptosis induction; autoprocessed caspase-4/11 binds the GSDMD-C domain with high affinity through a β-sheet interface induced by autoprocessing; crystal structures of caspase-4/11-GSDMD-C complexes reveal a hydrophobic GSDMD-binding interface unique to the p10 form, enabling substrate recognition independently of the canonical tetrapeptide cleavage-site sequence. Crystal structure determination of caspase-4/11-GSDMD-C complex, mutagenesis of autoprocessing sites, in vitro cleavage assays, affinity binding measurements Cell High 32109412
2020 Human GBP1 (guanylate-binding protein 1) binds LPS with high affinity through electrostatic interactions and associates with the surface of cytosolic Salmonella, recruiting GBP2-4 to form a GBP coat that then promotes caspase-4 recruitment to the bacterial surface and caspase-4 activation; GBPs are required for noncanonical inflammasome activation in human epithelial cells, identifying GBP1 as an upstream LPS sensor that assembles a platform for caspase-4 recruitment. GBP knockout cell lines, confocal microscopy of GBP and caspase-4 localization on cytosolic bacteria, LPS-binding assay with purified GBP1, pyroptosis and IL-1β assays Nature communications High 32581219

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 5307 26375003
1999 Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annual review of biochemistry 2196 10872455
2014 Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 1868 25119034
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
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2004 Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death. The Journal of cell biology 728 15123740
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma. Nature genetics 653 7951320
1999 Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB. The Journal of biological chemistry 621 10329646
2020 Structural Mechanism for GSDMD Targeting by Autoprocessed Caspases in Pyroptosis. Cell 587 32109412
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
1996 Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases. Proceedings of the National Academy of Sciences of the United States of America 489 8962078
2021 Gasdermin D pore structure reveals preferential release of mature interleukin-1. Nature 486 33883744
1998 Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation. Proceedings of the National Academy of Sciences of the United States of America 479 9539746
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2014 Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens. Cell host & microbe 371 25121752
2016 The All E. coli TX-TL Toolbox 2.0: A Platform for Cell-Free Synthetic Biology. ACS synthetic biology 330 26818434
1995 A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells. The EMBO journal 323 7743998
2015 NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5. European journal of immunology 322 26173988
2015 Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes. Nature communications 291 26508369
1991 IL-1-converting enzyme requires aspartic acid residues for processing of the IL-1 beta precursor at two distinct sites and does not cleave 31-kDa IL-1 alpha. Journal of immunology (Baltimore, Md. : 1950) 277 1919001
2015 Caspase-4 mediates non-canonical activation of the NLRP3 inflammasome in human myeloid cells. European journal of immunology 275 26174085
1995 Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases. The Journal of biological chemistry 274 7797592
2002 PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). The American journal of surgical pathology 268 12459622
2013 Protocols for implementing an Escherichia coli based TX-TL cell-free expression system for synthetic biology. Journal of visualized experiments : JoVE 267 24084388
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
1995 Identification and characterization of ICH-2, a novel member of the interleukin-1 beta-converting enzyme family of cysteine proteases. The Journal of biological chemistry 265 7797510
2022 Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3. Nature 233 35114687
2015 Human caspase-4 mediates noncanonical inflammasome activation against gram-negative bacterial pathogens. Proceedings of the National Academy of Sciences of the United States of America 229 25964352
2020 Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria. Nature communications 226 32581219
2003 A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23). Oncogene 215 12917640
2002 Interleukin-1F7B (IL-1H4/IL-1F7) is processed by caspase-1 and mature IL-1F7B binds to the IL-18 receptor but does not induce IFN-gamma production. Cytokine 209 12096920
1997 Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23). Oncogene 207 9010221
2013 Linear DNA for rapid prototyping of synthetic biological circuits in an Escherichia coli based TX-TL cell-free system. ACS synthetic biology 200 24303785
1996 The SSX-2 gene, which is involved in the t(X;18) translocation of synovial sarcomas, codes for the human tumor antigen HOM-MEL-40. Cancer research 193 8840996
2020 Biodegradable and Electroactive Regenerated Bacterial Cellulose/MXene (Ti3 C2 Tx ) Composite Hydrogel as Wound Dressing for Accelerating Skin Wound Healing under Electrical Stimulation. Advanced healthcare materials 189 32864898
1996 Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas. Proceedings of the National Academy of Sciences of the United States of America 178 8986805
2002 Monophasic fibrous and poorly differentiated synovial sarcoma: immunohistochemical reassessment of 60 t(X;18)(SYT-SSX)-positive cases. The American journal of surgical pathology 165 12409719
1994 Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family. Genes, chromosomes & cancer 155 7529552
2008 DIALIGN-TX: greedy and progressive approaches for segment-based multiple sequence alignment. Algorithms for molecular biology : AMB 136 18505568
2001 Detection of the synovial sarcoma translocation t(X;18) (SYT;SSX) in paraffin-embedded tissues using reverse transcriptase-polymerase chain reaction: a reliable and powerful diagnostic tool for pathologists. A molecular analysis of 221 mesenchymal tumors fixed in different fixatives. Human pathology 130 11172303
1997 The SYT protein involved in the t(X;18) synovial sarcoma translocation is a transcriptional activator localised in nuclear bodies. Human molecular genetics 125 9285794
2014 Rapidly characterizing the fast dynamics of RNA genetic circuitry with cell-free transcription-translation (TX-TL) systems. ACS synthetic biology 120 24621257
1988 Inherited prenatal hydrocephalus in the H-Tx rat: a morphological study. Neuropathology and applied neurobiology 114 3221976
2005 Loss of ZDHHC15 expression in a woman with a balanced translocation t(X;15)(q13.3;cen) and severe mental retardation. European journal of human genetics : EJHG 95 15915161
2002 Deficient cortical development in the hydrocephalic Texas (H-Tx) rat: a role for CSF. Brain : a journal of neurology 91 12135976
2010 TLE1 is a robust diagnostic biomarker for synovial sarcomas and correlates with t(X;18): analysis of 319 cases. European journal of cancer (Oxford, England : 1990) 82 20189377
2007 Mitochondrial structure and function in the untreated Jackson toxic milk (tx-j) mouse, a model for Wilson disease. Molecular genetics and metabolism 76 17981064
2006 The Vitamin D analogue TX 527 blocks NF-kappaB activation in peripheral blood mononuclear cells of patients with Crohn's disease. The Journal of steroid biochemistry and molecular biology 76 17049230
2001 Effect of the toxic milk mutation (tx) on the function and intracellular localization of Wnd, the murine homologue of the Wilson copper ATPase. Human molecular genetics 74 11157799
1996 Expression of p13MTCP1 is restricted to mature T-cell proliferations with t(X;14) translocations. Blood 70 8634440
2021 Ultrathin 2D Titanium Carbide MXene (Ti3 C2 Tx ) Nanoflakes Activate WNT/HIF-1α-Mediated Metabolism Reprogramming for Periodontal Regeneration. Advanced healthcare materials 64 34586717
2017 Streptomyces venezuelae TX-TL - a next generation cell-free synthetic biology tool. Biotechnology journal 64 28139884
1980 Primary and secondary nonrandom X chromosome inactivation in early female mouse embryos carrying Searle's translocation T(X; 16)16H. Chromosoma 64 7449570
2001 Impairment of MAD2B-PRCC interaction in mitotic checkpoint defective t(X;1)-positive renal cell carcinomas. Proceedings of the National Academy of Sciences of the United States of America 62 11717438
2023 Small-size Ti3C2Tx MXene nanosheets coated with metal-polyphenol nanodots for enhanced cancer photothermal therapy and anti-inflammation. Acta biomaterialia 57 36708854
1994 The t(X;18)(p11.2;q11.2) translocation found in human synovial sarcomas involves two distinct loci on the X chromosome. Oncogene 54 8152806
2002 SYT-SSX is critical for cyclin D1 expression in synovial sarcoma cells: a gain of function of the t(X;18)(p11.2;q11.2) translocation. Cancer research 53 12097301
1993 The chromosomal translocation t(X;14)(q28;q11) in T-cell pro-lymphocytic leukaemia breaks within one gene and activates another. Oncogene 52 8247530
2022 Ti3 C2 Tx MXene Composite 3D Hydrogel Potentiates mTOR Signaling to Promote the Generation of Functional Hair Cells in Cochlea Organoids. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 51 36117048
1992 Localization of the synovial sarcoma t(X;18)(p11.2;q11.2) breakpoint by fluorescence in situ hybridization. Human molecular genetics 48 1338692
2012 t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth. Blood 45 22966169
1996 A novel Krüppel-associated box containing the SSX gene (SSX3) on the human X chromosome is not implicated in t(X;18)-positive synovial sarcomas. Cytogenetics and cell genetics 42 8697803
2006 Rearrangement of the COL12A1 and COL4A5 genes in subungual exostosis: molecular cytogenetic delineation of the tumor-specific translocation t(X;6)(q13-14;q22). International journal of cancer 41 16284948
2006 Expression of the water-channel protein aquaporin 4 in the H-Tx rat: possible compensatory role in spontaneously arrested hydrocephalus. Journal of neurosurgery 41 17184078
2010 Minocycline inhibits glial proliferation in the H-Tx rat model of congenital hydrocephalus. Cerebrospinal fluid research 40 20507614
2006 Modified ELISPOT technique--highly significant inverse correlation of post-Tx donor-reactive IFNgamma-producing cell frequencies with 6 and 12 months graft function in kidney transplant recipients. Transplant immunology 39 17138059
1993 Identification of a yeast artificial chromosome (YAC) spanning the synovial sarcoma-specific t(X;18)(p11.2;q11.2) breakpoint. Genes, chromosomes & cancer 39 7682104
1990 Prenatal identification of a girl with a t(X;4)(p21;q35) translocation: molecular characterisation, paternal origin, and association with muscular dystrophy. Journal of medical genetics 39 2395160
1996 The effect of inherited hydrocephalus and shunt treatment on cortical pyramidal cell dendrites in the infant H-Tx rat. Experimental neurology 38 8812160
1993 Sublocalization of the synovial sarcoma-associated t(X;18) chromosomal breakpoint in Xp11.2 using cosmid cloning and fluorescence in situ hybridization. Oncogene 38 8389029
1984 Behavioral testing of progenies of Tx (hypothyroid) and growth hormone-treated Tx rats: an animal model for mental retardation. Neuroendocrinology 38 6539858
1994 The MTCP-1/c6.1B gene encodes for a cytoplasmic 8 kD protein overexpressed in T cell leukemia bearing a t(X;14) translocation. Oncogene 36 7970717
2011 t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34. Haematologica 35 22058210
2011 The t(X;6) in subungual exostosis results in transcriptional deregulation of the gene for insulin receptor substrate 4. International journal of cancer 33 20340132
2012 Biochemical, pharmacological, and structural characterization of new basic PLA2 Bbil-TX from Bothriopsis bilineata snake venom. BioMed research international 31 23509754
2021 Muscle Fatigue Sensor Based on Ti3 C2 Tx MXene Hydrogel. Small methods 29 34928032
2005 Translocation t(X;11)(q13;q23) in B-cell chronic lymphocytic leukemia disrupts two novel genes. Genes, chromosomes & cancer 29 15543602
2022 Accessory Genomes Drive Independent Spread of Carbapenem-Resistant Klebsiella pneumoniae Clonal Groups 258 and 307 in Houston, TX. mBio 28 35357213
2018 Kidney Transplantation in a Patient Lacking Cytosolic Phospholipase A2 Proves Renal Origins of Urinary PGI-M and TX-M. Circulation research 27 29298774
2016 Human genome meeting 2016 : Houston, TX, USA. 28 February - 2 March 2016. Human genomics 27 27294413
2006 The SYT-SSX fusion protein down-regulates the cell proliferation regulator COM1 in t(x;18) synovial sarcoma. Molecular and cellular biology 27 17101797
2000 The expression of inherited hydrocephalus in H-Tx rats. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 26 11048632
2021 Impact of a School-Based Gardening, Cooking, Nutrition Intervention on Diet Intake and Quality: The TX Sprouts Randomized Controlled Trial. Nutrients 25 34578959
2000 Effect of DT-TX 30, a combined thromboxane synthase inhibitor and thromboxane receptor antagonist, on retinal vascularity in experimental diabetes mellitus. Thrombosis research 25 10680643
2023 Biocompatible and Oxidation-Resistant Ti3 C2 Tx MXene with Halogen-Free Surface Terminations. Small methods 24 36929585
2002 Cryptic t(X;18), ins(6;18), and SYT-SSX2 gene fusion in a case of intraneural monophasic synovial sarcoma. Cancer genetics and cytogenetics 24 12505262
2001 Genome-wide linkage analysis of inherited hydrocephalus in the H-Tx rat. Mammalian genome : official journal of the International Mammalian Genome Society 24 11178739
2023 Ti3C2Tx MXene -facilitated non-selective trapping effect: Efficient SERS detection of exosomal PD-L1. Biosensors & bioelectronics 23 37364303
2004 Functional disomy of Xp including duplication of DAX1 gene with sex reversal due to t(X;Y)(p21.2;p11.3). American journal of medical genetics. Part A 23 15216557
2003 Endometrial stromal sarcoma with a sole t(X;17) chromosome change: report of a case and review of the literature. Gynecologic oncology 23 12648605
2001 Functional disomy for Xq26.3-qter in a boy with an unbalanced t(X;21)(q26.3;p11.2) translocation. American journal of medical genetics 23 11241467
2001 Chromosomal linkage associated with disease severity in the hydrocephalic H-Tx rat. Behavior genetics 23 11529267
2020 Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway. Evidence-based complementary and alternative medicine : eCAM 22 33456485
2018 Epigenetic changes of the thioredoxin system in the tx-j mouse model and in patients with Wilson disease. Human molecular genetics 22 30010856
2013 Vitamin D analogue TX 527 down-regulates the NF-κB pathway and controls the proliferation of endothelial cells transformed by Kaposi sarcoma herpesvirus. British journal of pharmacology 22 23647513
2008 Disruption of the IQSEC2 transcript in a female with X;autosome translocation t(X;20)(p11.2;q11.2) and a phenotype resembling X-linked infantile spasms (ISSX) syndrome. Molecular medicine reports 22 21479374
1990 The role of thromboxane (TX) A2 in rabbit arterial thrombosis induced by endothelial damage. Thrombosis research 22 2119075
2008 Inactivation of the CDKL3 gene at 5q31.1 by a balanced t(X;5) translocation associated with nonspecific mild mental retardation. American journal of medical genetics. Part A 21 18412109
2004 Relationship between plasma Cystatin C and creatinine in chronic renal diseases and Tx-transplant patients. Clinical biochemistry 21 14725938
2019 Functional iron deficiency in toxic milk mutant mice (tx-J) despite high hepatic ferroportin: a critical role of decreased GPI-ceruloplasmin expression in liver macrophages. Metallomics : integrated biometal science 20 31011744
2006 Minimal phenotype in a girl with trisomy 15q due to t(X;15)(q22.3;q11.2) translocation. American journal of medical genetics. Part A 20 16470732
2004 Angiogenesis inhibitor TX-1898: syntheses of the enantiomers of sterically diverse haloacetylcarbamoyl-2-nitroimidazole hypoxic cell radiosensitizers. Bioorganic & medicinal chemistry 20 15336271
1993 A mutant mouse (tx) with increased hepatic metallothionein stability and accumulation. The Biochemical journal 20 8257436
2013 Cell cycle arrest and apoptosis induced by 1α,25(OH)2D3 and TX 527 in Kaposi sarcoma is VDR dependent. The Journal of steroid biochemistry and molecular biology 19 24316429
2000 Hydrocephalus in the H-Tx rat: a monogenic disease? Experimental neurology 19 10785451
2003 Antiangiogenic hypoxic cytotoxin TX-402 inhibits hypoxia-inducible factor 1 signaling pathway. Anticancer research 18 14666730
2023 Nanoenzyme-Reinforced Multifunctional Scaffold Based on Ti3C2Tx MXene Nanosheets for Promoting Structure-Functional Skeletal Muscle Regeneration via Electroactivity and Microenvironment Management. Nano letters 17 37578316
1994 Clonal evolution of malignant and non-malignant T cells carrying t(14;14) and t(X;14) in patients with ataxia telangiectasia. Oncogene 17 8036021
2023 Surface Functional Modification by Ti3 C2 Tx MXene on PLLA Nanofibers for Optimizing Neural Stem Cell Engineering. Advanced healthcare materials 16 37341969
2022 Ti3C2Tx MXene nanosheets enhance the tolerance of Torreya grandis to Pb stress. Journal of hazardous materials 16 37056011
2021 Tuning Cell-Free Composition Controls the Time Delay, Dynamics, and Productivity of TX-TL Expression. ACS synthetic biology 16 34498860
2006 Combustion-generated nanoparticulates in the El Paso, TX, USA / Juarez, Mexico Metroplex: their comparative characterization and potential for adverse health effects. International journal of environmental research and public health 16 16823077
1993 Association of HSP72 with the nuclear (TX-100-insoluble) fraction upon heating tolerant and non-tolerant HeLa S3 cells. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 16 8433029
2022 Coupling W18 O49 /Ti3 C2 Tx MXene Pseudocapacitive Electrodes with Redox Electrolytes to Construct High-Performance Asymmetric Supercapacitors. Small (Weinheim an der Bergstrasse, Germany) 15 36344426
2020 Feeding Habits of Vector Mosquitoes in Harris County, TX, 2018. Journal of medical entomology 15 32574364
2008 Molecular and cytogenetic analysis of the spreading of X inactivation in a girl with microcephaly, mild dysmorphic features and t(X;5)(q22.1;q31.1). European journal of human genetics : EJHG 15 18301446
2008 Analysis of neuronal cell death in the cerebral cortex of H-Tx rats with compensated hydrocephalus. Journal of neurosurgery. Pediatrics 15 18352806
2004 Analysis of TGF-beta2 and TGF-beta3 expression in the hydrocephalic H-Tx rat brain. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 15 15375625
2001 Fate of the biological control agent Pseudomonas aureofaciens TX-1 after application to turfgrass. Applied and environmental microbiology 15 11472930
2019 In vitro studies revealed a downregulation of Wnt/β-catenin cascade by active vitamin D and TX 527 analog in a Kaposi's sarcoma cellular model. Toxicology in vitro : an international journal published in association with BIBRA 14 31838186
2011 Spread of X-chromosome inactivation into chromosome 15 is associated with Prader-Willi syndrome phenotype in a boy with a t(X;15)(p21.1;q11.2) translocation. Human genetics 14 21735174
2006 Heterotaxy and cardiac defect in a girl with chromosome translocation t(X;1)(q26;p13.1) and involvement of ZIC3. European journal of human genetics : EJHG 14 16926859
2002 Nonrandom X chromosome inactivation in mouse embryos carrying Searle's T(X;16)16H translocation visualized using X-linked LACZ and GFP transgenes. Cytogenetic and genome research 14 12900545
2023 Ti3 C2 TX MXene Ink Direct Writing Flexible Sensors for Disposable Paper Toys. Small (Weinheim an der Bergstrasse, Germany) 13 37162447
2000 Molecular cytogenetics of t(X;1)(p11.2;q21) with complex rearrangements in a renal cell carcinoma. Cancer genetics and cytogenetics 13 11120337
1999 Acute myeloid leukemia with hypergranular cytoplasm accompanied by t(X;11)(q24;q23) and rearrangement of the MLL gene. Leukemia research 13 9933140