Affinage

ASPSCR1

Tether containing UBX domain for GLUT4 · UniProt Q9BZE9

Length
553 aa
Mass
60.2 kDa
Annotated
2026-06-09
100 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASPSCR1 (TUG/ASPL/UBXD9) is a multifunctional tethering protein that controls insulin-regulated vesicle trafficking and that, when fused to TFE3, becomes a sarcoma-driving oncogenic transcription factor (PMID:17202135, PMID:36246906, PMID:37029109). In fat and muscle, intact TUG traps GLUT4 storage vesicles intracellularly by binding GLUT4 through its N-terminal region and the Golgi matrix through its acetylated C-terminus, holding vesicles in perinuclear membranes until insulin acts (PMID:17202135, PMID:22610098, PMID:36246906); its N-terminus adopts a ubiquitin-like beta-grasp fold that serves as a protein-interaction module rather than a covalent modifier (PMID:16501224). Insulin triggers site-specific endoproteolytic cleavage of TUG by the muscle splice form of the Usp25 protease in a TC10α-dependent manner, releasing vesicles for translocation; the N-terminal TUGUL product modifies the KIF5B kinesin to load cargo onto microtubule motors, while the C-terminal product enters the nucleus to bind PPARγ/PGC-1α and drive fatty acid oxidation and thermogenesis, with its stability controlled by the ATE1 N-degron pathway (PMID:22610098, PMID:29773651, PMID:33686286). This proteolytic switch governs coordinated translocation of both GLUT4 and IRAP and regulates systemic glucose homeostasis and energy expenditure in vivo (PMID:23744065, PMID:25944897). Independently, TUG binds the p97/VCP AAA-ATPase N-terminal domain through an extended UBX domain and stoichiometrically disassembles p97 hexamers into p97:ASPL heterotetramers with loss of D2 ATPase activity, regulating ERAD, membrane trafficking, and Golgi reassembly (PMID:22207755, PMID:27762274). In alveolar soft part sarcoma, the der(17)t(X;17) translocation fuses ASPSCR1 in-frame to TFE3, producing a nuclear oncoprotein that acts as a strong transactivator binding thousands of genomic loci and directly upregulating MET, CYP17A1, and other targets (PMID:11244503, PMID:23288701); in vivo it remodels super-enhancers to drive angiogenesis via Pdgfb, Rab27a, and Sytl2, activates lysosome-autophagy programs, and induces p21-dependent senescence with SASP secretion (PMID:37029109, PMID:33846569, PMID:27673450).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 High

    Established that ASPSCR1 is recurrently disrupted by chromosomal translocation, defining its oncogenic relevance and revealing a C-terminal UBX-like domain.

    Evidence RT-PCR, cDNA sequencing, and FISH across alveolar soft part sarcoma cases

    PMID:11244503

    Open questions at the time
    • Did not establish how the fusion deregulates transcription
    • Did not characterize the normal function of the UBX-like domain
  2. 2006 Medium

    Determined that the N-terminal TUG region folds as a ubiquitin-like domain lacking the diglycine motif, indicating a protein-interaction rather than conjugation role.

    Evidence NMR solution structure of the isolated UBL1 domain

    PMID:16501224

    Open questions at the time
    • No functional mutagenesis in the same study
    • Binding partners of the UBL1 domain not identified structurally
  3. 2007 High

    Identified TUG's physiological role: it directly binds GLUT4 and sequesters it intracellularly, making it a gatekeeper of insulin-responsive glucose uptake.

    Evidence siRNA knockdown, dominant-negative fragment, microscopy, binding and glucose-uptake assays in 3T3-L1 adipocytes

    PMID:17202135

    Open questions at the time
    • Mechanism of insulin-triggered release not defined
    • Did not identify the C-terminal anchoring partner
  4. 2011 High

    Revealed a trafficking-regulatory function distinct from GLUT4: TUG binds the p97/VCP N-domain and disassembles p97 hexamers at the ERGIC/ER exit sites.

    Evidence Co-IP, in vitro disassembly assays, domain mapping, and brefeldin A washout in cells

    PMID:22207755

    Open questions at the time
    • Structural basis of hexamer disassembly not resolved
    • Relationship between p97 binding and GLUT4 tethering unclear
  5. 2012 High

    Defined the molecular switch: insulin drives site-specific TUG cleavage that severs the GLUT4-binding from the Golgi-anchoring half, releasing vesicles.

    Evidence Cleavage-resistant mutant rescue, TC10α RNAi epistasis, Co-IP, and glucose-uptake assays

    PMID:22610098

    Open questions at the time
    • The protease responsible was not identified
    • Fate of the cleavage products not established
  6. 2013 High

    Showed the TUG proteolytic pathway controls systemic physiology, linking cleavage to glucose turnover and whole-body energy expenditure in muscle.

    Evidence Muscle-specific UBX-Cter transgenic mice, hyperinsulinemic clamp, and indirect calorimetry

    PMID:23744065

    Open questions at the time
    • Did not define the nuclear effectors of energy expenditure
    • Mechanism connecting cleavage to thermogenesis unresolved
  7. 2013 High

    Demonstrated that the ASPSCR1-TFE3 fusion is a nuclear transactivator with genome-wide binding and proliferation-promoting targets, providing the transcriptional mechanism implied in 2001.

    Evidence Nuclear localization, genome-wide ChIP-seq, inducible expression, and an RNAi target screen

    PMID:23288701

    Open questions at the time
    • Did not address in vivo tumor requirement
    • Chromatin/enhancer mechanism not yet defined
  8. 2015 High

    Established post-translational control of TUG by acetylation, with SIRT2 deacetylation tuning GLUT4/IRAP trafficking and proteolysis.

    Evidence Acetylation MS, Co-IP, mutagenesis, RNAi, and SIRT2 knockout mice with glucose tolerance tests

    PMID:25561724

    Open questions at the time
    • Acetyltransferase (writer) not identified
    • How acetylation influences cleavage kinetics unresolved
  9. 2015 High

    Extended TUG's cargo control beyond GLUT4 to IRAP, showing coordinated regulation of multiple vesicle cargoes with measurable physiological consequences.

    Evidence Transgenic mice, recombinant binding mapping, Co-IP, and in vivo vasopressin/copeptin assays

    PMID:25944897

    Open questions at the time
    • Full cargo repertoire not enumerated
    • Tissue specificity of cargo selection unclear
  10. 2016 High

    Provided the structural mechanism of p97 regulation: an extended UBX domain converts hexamers into stable heterotetramers, reorienting D2 and abolishing its ATPase activity.

    Evidence X-ray crystallography, quantitative interaction mapping, ATPase and ERAD assays

    PMID:27762274

    Open questions at the time
    • Physiological trigger for disassembly in cells not defined
    • Reversal of disassembly not characterized
  11. 2016 Medium

    Connected ASPSCR1-mediated p97 disassembly to disease, showing pathogenic p97 mutations reduce disassembly efficiency.

    Evidence Co-IP, pull-down, surface plasmon resonance, and density-gradient disassembly assays

    PMID:27132113

    Open questions at the time
    • Single lab without orthogonal cellular validation
    • Disease relevance of altered disassembly not demonstrated in vivo
  12. 2016 Medium

    Showed the ASPL-TFE3 fusion drives p53-independent p21 activation, cell-cycle arrest, and senescence with SASP secretion, adding a growth-modulatory facet to the oncoprotein.

    Evidence Reporter assay, RT-PCR, SA-β-gal staining, p21 RNAi rescue, and inducible expression in MSCs

    PMID:27673450

    Open questions at the time
    • Single-lab evidence
    • Reconciliation of senescence with tumor proliferation unresolved
  13. 2018 High

    Identified the protease and the downstream effector of TUG cleavage: muscle Usp25m generates TUGUL, which modifies KIF5B to load GLUT4 onto microtubule motors, and is reduced in insulin resistance.

    Evidence Isoform-specific reconstitution, Co-IP, in vitro proteolysis, colocalization, and diet-induced insulin resistance mice

    PMID:29773651

    Open questions at the time
    • Mechanism of TUGUL attachment to KIF5B not structurally defined
    • Regulation of Usp25m isoform expression unresolved
  14. 2021 High

    Defined the nuclear function of the C-terminal cleavage product, linking TUG proteolysis to PPARγ/PGC-1α-driven lipid oxidation/thermogenesis and to ATE1 N-degron-controlled stability.

    Evidence Muscle-specific knockout and constitutive-cleavage mice, nuclear Co-IP, calorimetry, and ATE1 knockout

    PMID:33686286

    Open questions at the time
    • Direct transcriptional targets of the nuclear product not enumerated
    • Mechanism coupling cleavage to nuclear entry unresolved
  15. 2021 Medium

    Showed the ASPL-TFE3 fusion in renal cell carcinoma activates lysosome-autophagy genes and bypasses mTOR-TFE3 regulation to enable energy-stress evasion.

    Evidence Nuclear localization, promoter binding, autophagy flux, mTOR inhibition, and proliferation assays

    PMID:33846569

    Open questions at the time
    • Single-lab evidence
    • Mechanism of escape from mTOR regulation not fully defined
  16. 2023 High

    Established that ASPSCR1::TFE3 is dispensable in vitro but required for in vivo tumor angiogenesis through super-enhancer remodeling and activation of vesicle-trafficking genes.

    Evidence Conditional in vivo knockdown, CUT&RUN/ChIP-seq super-enhancer mapping, and dCas9 epigenomic CRISPR screen

    PMID:37029109

    Open questions at the time
    • Direct mechanism of super-enhancer recruitment unresolved
    • Whether normal ASPSCR1 functions contribute to fusion activity unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the normal trafficking/p97-regulatory functions of ASPSCR1 relate to the oncogenic activity of the ASPSCR1-TFE3 fusion, and whether retained ASPSCR1 domains shape fusion behavior, remains unresolved.
  • No study connects TUG's tethering/p97 biology to fusion oncogenesis
  • Contribution of the UBX/UBL domains to the fusion protein not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3 GO:0031386 protein tag activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005783 endoplasmic reticulum 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-382551 Transport of small molecules 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-392499 Metabolism of proteins 2
Partners
ACBD3GLUT4GOLGIN-160KIF5BPPARGSIRT2USP25VCP
Complex memberships
ASPSCR1-TFE3 fusion transcription factorGLUT4 storage vesicle tethering complexp97/VCP:ASPL heterotetramer

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 ASPSCR1 (ASPL) at 17q25 is fused in-frame to the TFE3 transcription factor gene at Xp11.2 via the der(17)t(X;17)(p11.2;q25) translocation in alveolar soft part sarcoma, generating ASPL-TFE3 fusion proteins (type 1 and type 2) that retain the TFE3 DNA-binding domain, implying transcriptional deregulation as the oncogenic mechanism. The ASPL protein contains a UBX-like domain in its C-terminal region. Southern blotting, RT-PCR, cDNA sequencing, FISH Oncogene High 11244503
2007 TUG (ASPSCR1) directly binds GLUT4 via a large intracellular loop in GLUT4, retains GLUT4 in perinuclear (non-endosomal) membranes in unstimulated 3T3-L1 adipocytes, and is required for intracellular sequestration of GLUT4; siRNA-mediated depletion or dominant-negative TUG expression causes GLUT4 translocation and enhanced glucose uptake resembling insulin stimulation. siRNA knockdown, dominant-negative overexpression, fluorescence microscopy, glucose uptake assay, direct binding assay The Journal of biological chemistry High 17202135
2011 TUG (ASPSCR1) binds p97/VCP at its N-terminal domain via an extended sequence comprising three TUG regions (not the UBX domain alone), causes stoichiometric conversion of p97 hexamers into monomers (hexamer disassembly), and localizes to the ER-to-Golgi intermediate compartment (ERGIC) and ER exit sites. TUG overexpression accumulates ubiquitylated substrates and targets p97 to the nucleus; TUG depletion impairs Golgi reassembly after brefeldin A removal. Co-immunoprecipitation, in vitro binding/disassembly assays, siRNA knockdown, immunofluorescence, brefeldin A washout assay The Journal of biological chemistry High 22207755
2012 Insulin stimulates site-specific endoproteolytic cleavage of TUG (ASPSCR1) in adipocytes in a TC10α-dependent manner, separating an N-terminal GLUT4-binding fragment (generating an 18-kDa ubiquitin-like modifier called TUGUL) from a C-terminal fragment that had bound the Golgi matrix anchor. Intact TUG links GLUT4 to PIST (a TC10α effector) and to Golgin-160 via its C-terminus. A cleavage-resistant TUG mutant does not support insulin-responsive GLUT4 translocation or glucose uptake. Site-specific mutagenesis (cleavage-resistant mutant), RNAi (TC10α knockdown), co-immunoprecipitation, immunoblotting, glucose uptake assay, cell fractionation The Journal of biological chemistry High 22610098
2013 Muscle-specific transgenic expression of the TUG C-terminal UBX-Cter fragment in mice causes constitutive TUG proteolysis and GLUT4 translocation to T-tubules during fasting, decreases fasting plasma glucose and insulin, increases whole-body glucose turnover, and elevates oxygen consumption and energy expenditure by 12–13%, demonstrating that the TUG proteolytic pathway regulates systemic glucose homeostasis and energy metabolism in muscle. Tissue-specific transgenic mouse model, hyperinsulinemic clamp, 2-deoxyglucose uptake, cell fractionation, indirect calorimetry The Journal of biological chemistry High 23744065
2013 ASPSCR1-TFE3 fusion protein localizes predominantly to the nucleus, functions as a stronger transcriptional transactivator than native TFE3, binds 2193 genomic loci genome-wide, and up-regulates direct target genes including MET, CYP17A1, and UPP1. RNAi screening identified 11 additional ASPSCR1-TFE3 target genes that contribute to cancer cell proliferation. Nuclear localization assay, genome-wide ChIP-seq (location analysis), inducible expression system, RNAi high-throughput screen, reporter assay The Journal of pathology High 23288701
2015 TUG (ASPSCR1) C-terminus is acetylated; acetylation reduces binding of TUG to ACBD3 (but not Golgin-160), and mutation of acetylated residues impairs insulin-responsive GLUT4 trafficking. SIRT2 deacetylase binds TUG, deacetylates it, and its overexpression redistributes GLUT4 and IRAP to the plasma membrane. SIRT2 knockout mice show increased TUG acetylation and proteolytic processing and enhanced glucose disposal. Mass spectrometry/acetylation detection, co-immunoprecipitation, site-directed mutagenesis, RNAi, SIRT2 knockout mouse, glucose tolerance test The Journal of biological chemistry High 25561724
2015 TUG proteolysis controls IRAP (insulin-regulated aminopeptidase) targeting to T-tubules in muscle as well as GLUT4 translocation; IRAP binds TUG through a short peptide previously shown critical for GLUT4 intracellular retention. Constitutive TUG proteolysis in transgenic mice increases vasopressin degradation in vivo, demonstrating that TUG controls coordinated translocation of both GLUT4 and IRAP vesicle cargoes. Transgenic mouse model, recombinant protein binding/mapping, co-immunoprecipitation, cell fractionation, vasopressin/copeptin assay, renal AQP2 measurement The Journal of biological chemistry High 25944897
2016 ASPSCR1 (ASPL) contains an extended UBX domain (eUBX) that is critical for disassembly of p97 hexamers, generating stable p97:ASPL heterotetramers. Hexamer disassembly is accompanied by reorientation of the p97 D2 ATPase domain and loss of D2 ATPase activity. Overproduction of ASPL disrupts p97 hexamer function in ERAD. Quantitative interaction mapping, high-resolution structural studies (X-ray crystallography), biochemical disassembly assays, ATPase activity assay, ERAD functional assay Nature communications High 27762274
2016 ASPL-TFE3 fusion oncoprotein functions as an aberrant transcription factor that directly activates p21 (CDKN1A) expression in a p53-independent manner through binding to the p21 promoter, causing cell cycle arrest and cellular senescence; senescent cells secrete proinflammatory SASP cytokines. Ectopic expression, luciferase reporter assay, RT-PCR, senescence-associated β-galactosidase staining, RNAi (p21 knockdown), tetracycline-inducible expression in mesenchymal stem cells Neoplasia Medium 27673450
2016 Mutant p97 (disease-causing R93C, R155H, R155C) reduces the efficiency of UBXD9/TUG (ASPSCR1)/ASPL-mediated p97 hexamer disassembly into monomers, with species- and mutation-specific differences in binding affinity (assessed by surface plasmon resonance) and ATP-dependent interactions. Co-immunoprecipitation, pull-down assay, surface plasmon resonance, sucrose density gradient ultracentrifugation, ATPase activity measurement European journal of cell biology Medium 27132113
2018 The muscle splice form of Usp25 (Usp25m), but not the Usp25a isoform, is the protease required for insulin-stimulated TUG cleavage and GLUT4 translocation in adipocytes. Usp25m binds TUG and GLUT4, colocalizes with TUG in unstimulated cells, and dissociates from TUG-bound vesicles after insulin. TUG cleavage generates TUGUL, which modifies the KIF5B kinesin motor, and this is required to load GLUT4 onto microtubule-based motors. TUG proteolysis and Usp25m are reduced in insulin-resistant adipose tissue. Co-immunoprecipitation, RNAi knockdown, transfection reconstitution (isoform specificity), in vitro proteolysis assay, immunofluorescence/colocalization, diet-induced insulin resistance mouse model The Journal of biological chemistry High 29773651
2021 Insulin-stimulated TUG (Aspscr1) cleavage in muscle releases a C-terminal cleavage product that enters the nucleus, binds PPARγ and PGC-1α, and regulates gene expression to promote lipid oxidation and thermogenesis, upregulating sarcolipin in muscle and UCP1 in adipocytes. This pathway is independent of PI3K/Akt. The PPARγ2 Pro12Ala polymorphism (associated with reduced diabetes risk) enhances TUG binding. The ATE1 arginyltransferase regulates stability of the TUG C-terminal product via an N-degron pathway. Muscle-specific Tug knockout and constitutive-cleavage mouse models confirmed regulation of insulin-stimulated glucose uptake and whole-body energy expenditure. Muscle-specific Aspscr1 knockout mice, muscle-specific constitutive TUG cleavage mice, nuclear co-immunoprecipitation (PPARγ/PGC-1α binding), gene expression analysis, indirect calorimetry, ATE1 knockout, glucose/insulin tolerance tests Nature metabolism High 33686286
2022 TUG (Aspscr1, UBXD9) proteins act as central tethers that trap GLUT4 storage vesicles at the Golgi matrix via N-terminal GLUT4-binding and C-terminal Golgi matrix-binding; insulin triggers Usp25m-mediated endoproteolytic cleavage generating the TUGUL ubiquitin-like modifier (N-terminal product) that modifies KIF5B kinesin in adipocytes, enabling microtubule-based vesicle transport to the cell surface. After cleavage, the TUG C-terminal product is extracted from the Golgi matrix by p97/VCP ATPase. In both muscle and fat, the C-terminal product enters the nucleus to bind PPARγ/PGC-1α and regulate fatty acid oxidation. Stability of the C-terminal product is regulated by Ate1-dependent N-degron pathway. Review integrating genetic mouse models, biochemical reconstitution, co-immunoprecipitation, and functional assays from multiple prior studies Frontiers in endocrinology Medium 36246906
2006 The N-terminal region of TUG (ASPSCR1; residues 10–83) adopts a ubiquitin-like (beta-grasp) fold as determined by NMR spectroscopy. This UBL1 domain lacks the C-terminal diglycine motif and canonical ubiquitin 'Ile-44 hydrophobic face', suggesting it functions as a protein-protein interaction module rather than as a covalent modifier. NMR spectroscopy (solution structure and backbone dynamics) Protein science Medium 16501224
2023 ASPSCR1::TFE3 fusion transcription factor is dispensable for in vitro tumor cell maintenance but is required for in vivo tumor development via angiogenesis. ASPSCR1::TFE3 associates with super-enhancers (SEs) at its DNA binding sites; its loss causes SE redistribution affecting angiogenesis pathway genes. ASPSCR1::TFE3 transcriptionally activates Pdgfb, Rab27a, Sytl2, and Vwf; Rab27a and Sytl2 promote angiogenic factor trafficking to facilitate ASPS vascular network construction. Conditional knockdown (in vitro vs. in vivo comparison), CUT&RUN/ChIP-seq (SE mapping), epigenomic CRISPR/dCas9 functional screen, gene expression analysis Nature communications High 37029109
2021 ASPL-TFE3 fusion protein translocates to the nucleus in renal cell carcinoma cells and transcriptionally activates lysosome-autophagy pathway genes by binding their promoters. This autophagy activation enables energy stress evasion by promoting protein and lipid utilization. The fusion protein escapes regulation by the classic mTOR-TFE3 signaling axis and instead activates phospho-mTOR and its downstream targets. Nuclear localization assay, ChIP/promoter binding assay, autophagy flux assay, mTOR pathway inhibition, in vitro and in vivo proliferation assay Oncogene Medium 33846569

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Genomic imprinting in mammalian development: a parental tug-of-war. Trends in genetics : TIG 859 2035190
2001 Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. The American journal of pathology 487 11438465
2001 The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 458 11244503
2005 Kinesin and dynein move a peroxisome in vivo: a tug-of-war or coordinated movement? Science (New York, N.Y.) 425 15817813
2019 PARP Inhibitor Resistance: A Tug-of-War in BRCA-Mutated Cells. Trends in cell biology 371 31421928
2012 Tug-of-war in motor protein ensembles revealed with a programmable DNA origami scaffold. Science (New York, N.Y.) 307 23065903
2020 A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses. Emerging microbes & infections 253 32172672
2009 Tug-of-war between dissimilar teams of microtubule motors regulates transport and fission of endosomes. Proceedings of the National Academy of Sciences of the United States of America 252 19864630
2013 The pharmacology of TUG-891, a potent and selective agonist of the free fatty acid receptor 4 (FFA4/GPR120), demonstrates both potential opportunity and possible challenges to therapeutic agonism. Molecular pharmacology 180 23979972
2019 The Iron Tug-of-War between Bacterial Siderophores and Innate Immunity. Journal of innate immunity 124 30605903
2022 Molecular tug-of-war: Plant immune recognition of herbivory. The Plant cell 117 35026025
2014 Tug-of-war between driver and passenger mutations in cancer and other adaptive processes. Proceedings of the National Academy of Sciences of the United States of America 104 25277973
2002 Nuclear-cytoplasmic "tug of war" during cloning: effects of somatic cell nuclei on culture medium preferences of preimplantation cloned mouse embryos. Biology of reproduction 100 11906939
2024 A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle. Journal of experimental & clinical cancer research : CR 99 38459595
2018 The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat. EMBO molecular medicine 87 29343498
2011 Switches and latches: a biochemical tug-of-war between the kinases and phosphatases that control mitosis. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 84 22084385
2007 The glucose transporter 4-regulating protein TUG is essential for highly insulin-responsive glucose uptake in 3T3-L1 adipocytes. The Journal of biological chemistry 80 17202135
2019 Cell sensing and decision-making in confinement: The role of TRPM7 in a tug of war between hydraulic pressure and cross-sectional area. Science advances 72 31355337
2011 Detection of ASPL/TFE3 fusion transcripts and the TFE3 antigen in formalin-fixed, paraffin-embedded tissue in a series of 18 cases of alveolar soft part sarcoma: useful diagnostic tools in cases with unusual histological features. Virchows Archiv : an international journal of pathology 66 21279521
2019 The Tug-of-War between Plants and Viruses: Great Progress and Many Remaining Questions. Viruses 60 30823402
2019 A Tug-of-War between Cell Shape and Polarity Controls Division Orientation to Ensure Robust Patterning in the Mouse Blastocyst. Developmental cell 60 31735668
2013 Combining integrated genomics and functional genomics to dissect the biology of a cancer-associated, aberrant transcription factor, the ASPSCR1-TFE3 fusion oncoprotein. The Journal of pathology 60 23288701
2013 A subcellular tug of war involving three MYB-like proteins underlies a molecular antagonism in Antirrhinum flower asymmetry. The Plant journal : for cell and molecular biology 58 23638688
2013 Assembly of the type II secretion system such as found in Vibrio cholerae depends on the novel Pilotin AspS. PLoS pathogens 55 23326233
2008 Axonal degeneration and regeneration: a mechanistic tug-of-war. Journal of neurochemistry 55 19054282
2015 Tug of war--the influence of opposing physical forces on epithelial cell morphology. Developmental biology 53 25576028
2011 Clustering of GLUT4, TUG, and RUVBL2 protein levels correlate with myosin heavy chain isoform pattern in skeletal muscles, but AS160 and TBC1D1 levels do not. Journal of applied physiology (Bethesda, Md. : 1985) 52 21799128
2015 Acetylation of TUG protein promotes the accumulation of GLUT4 glucose transporters in an insulin-responsive intracellular compartment. The Journal of biological chemistry 49 25561724
2012 Endoproteolytic cleavage of TUG protein regulates GLUT4 glucose transporter translocation. The Journal of biological chemistry 49 22610098
2011 The ubiquitin regulatory X (UBX) domain-containing protein TUG regulates the p97 ATPase and resides at the endoplasmic reticulum-golgi intermediate compartment. The Journal of biological chemistry 49 22207755
2007 Detection of the ASPSCR1-TFE3 gene fusion in paraffin-embedded alveolar soft part sarcomas. Histopathology 49 17543078
2022 Translation-A tug of war during viral infection. Molecular cell 48 36334591
2012 Competitive cell interactions in cancer: a cellular tug of war. Trends in cell biology 47 23219382
2019 A Tug of War: DNA-Sensing Antiviral Innate Immunity and Herpes Simplex Virus Type I Infection. Frontiers in microbiology 43 31849849
2009 The PI3K-PTEN tug-of-war, oxidative stress and retinal degeneration. Trends in molecular medicine 43 19380252
2001 aspS encoding an unusual aspartyl protease from Sclerotinia sclerotiorum is expressed during phytopathogenesis. FEMS microbiology letters 41 11150661
2019 Bacterial Manipulation of Wnt Signaling: A Host-Pathogen Tug-of-Wnt. Frontiers in immunology 40 31681283
2016 Quantitative interaction mapping reveals an extended UBX domain in ASPL that disrupts functional p97 hexamers. Nature communications 40 27762274
2018 Usp25m protease regulates ubiquitin-like processing of TUG proteins to control GLUT4 glucose transporter translocation in adipocytes. The Journal of biological chemistry 39 29773651
2011 Technique for differentiating alveolar soft part sarcoma from other tumors in paraffin-embedded tissue: comparison of immunohistochemistry for TFE3 and CD147 and of reverse transcription polymerase chain reaction for ASPSCR1-TFE3 fusion transcript. Human pathology 39 21835426
2022 A Tug of War: Pseudorabies Virus and Host Antiviral Innate Immunity. Viruses 37 35336954
2021 Interferons: Tug of War Between Bacteria and Their Host. Frontiers in cellular and infection microbiology 37 33777837
1988 Simultaneous analysis of multiple polymorphic loci using amplified sequence polymorphisms (ASPs). Genomics 36 2906038
2020 Tug-of-war between actomyosin-driven antagonistic forces determines the positioning symmetry in cell-sized confinement. Nature communications 35 32541780
2002 Identification and characterization of novel small RNAs in the aspS-yrvM intergenic region of the Bacillus subtilis genome. Microbiology (Reading, England) 34 12177353
2019 Winning the Tug-of-War Between Effector Gene Design and Pathogen Evolution in Vector Population Replacement Strategies. Frontiers in genetics 32 31737050
2021 Insulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake. Nature metabolism 31 33686286
2020 Catalysis of proline isomerization and molecular chaperone activity in a tug-of-war. Nature communications 31 33247146
2018 Tug of war between Acinetobacter baumannii and host immune responses. Pathogens and disease 31 30657912
2009 Therapeutic vulnerability of an in vivo model of alveolar soft part sarcoma (ASPS) to antiangiogenic therapy. Journal of pediatric hematology/oncology 31 19636271
2019 Controlling DNA Tug-of-War in a Dual Nanopore Device. Small (Weinheim an der Bergstrasse, Germany) 30 31192541
2017 Tiam1/Vav2-Rac1 axis: A tug-of-war between islet function and dysfunction. Biochemical pharmacology 30 28202288
2024 Patterns of recombination in snakes reveal a tug-of-war between PRDM9 and promoter-like features. Science (New York, N.Y.) 29 38386752
2022 PEComa-like Neoplasms Characterized by ASPSCR1-TFE3 Fusion: Another Face of TFE3-related Mesenchymal Neoplasia. The American journal of surgical pathology 28 35848761
2022 ASPS Exhibits Anti-Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ-Glutamylcysteine Level. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 28 36417588
2018 Biomechanical Control of Lysosomal Secretion Via the VAMP7 Hub: A Tug-of-War between VARP and LRRK1. iScience 28 30240735
2014 Biochemical and structural characterization of mycobacterial aspartyl-tRNA synthetase AspS, a promising TB drug target. PloS one 28 25409504
2008 Alveolar soft part sarcoma: a bimarker diagnostic strategy using TFE3 immunoassay and ASPL-TFE3 fusion transcripts in paraffin-embedded tumor tissues. Diagnostic molecular pathology : the American journal of surgical pathology, part B 28 18382356
2024 Entropy Tug-of-War Determines Solvent Effects in the Liquid-Liquid Phase Separation of a Globular Protein. The journal of physical chemistry letters 27 38580324
2023 ASPSCR1::TFE3 orchestrates the angiogenic program of alveolar soft part sarcoma. Nature communications 27 37029109
2016 ASPL-TFE3 Oncoprotein Regulates Cell Cycle Progression and Induces Cellular Senescence by Up-Regulating p21. Neoplasia (New York, N.Y.) 27 27673450
2021 Nuclear translocation of ASPL-TFE3 fusion protein creates favorable metabolism by mediating autophagy in translocation renal cell carcinoma. Oncogene 26 33846569
2021 A glutamine 'tug-of-war': targets to manipulate glutamine metabolism for cancer immunotherapy. Immunotherapy advances 26 34541580
2021 Metallo-β-lactamases and a tug-of-war for the available zinc at the host-pathogen interface. Current opinion in chemical biology 26 34864439
2020 Viral non-coding RNAs: Stealth strategies in the tug-of-war between humans and herpesviruses. Seminars in cell & developmental biology 26 32631785
2013 Enhanced fasting glucose turnover in mice with disrupted action of TUG protein in skeletal muscle. The Journal of biological chemistry 25 23744065
2016 Engineered Tug-of-War Between Kinesin and Dynein Controls Direction of Microtubule Based Transport In Vivo. Traffic (Copenhagen, Denmark) 24 26843027
2015 Hepatitis C virus and antiviral innate immunity: who wins at tug-of-war? World journal of gastroenterology 24 25852264
2016 A tug-of-war between tolerance and rejection - New evidence for 3'UTR HLA-G haplotypes influence in recurrent pregnancy loss. Human immunology 23 27397898
2014 Tug of war between survival and death: exploring ATM function in cancer. International journal of molecular sciences 23 24681585
2021 FFAR1/GPR40: One target, different binding sites, many agonists, no drugs, but a continuous and unprofitable tug-of-war between ligand lipophilicity, activity, and toxicity. Bioorganic & medicinal chemistry letters 22 33771587
2009 Direct observation of tug-of-war during the folding of a mutually exclusive protein. Journal of the American Chemical Society 22 19719116
2015 Coordinated Regulation of Vasopressin Inactivation and Glucose Uptake by Action of TUG Protein in Muscle. The Journal of biological chemistry 21 25944897
2012 Robustness analysis of cellular systems using the genetic tug-of-war method. Molecular bioSystems 21 22722869
2021 NK Cells in a Tug-of-War With Cancer: The Roles of Transcription Factors and Cytoskeleton. Frontiers in immunology 20 34594338
2021 Weak multivalent biomolecular interactions: a strength versus numbers tug of war with implications for phase partitioning. RNA (New York, N.Y.) 20 34772790
2012 Giving the right tug for migration: cadherins in tissue movements. Archives of biochemistry and biophysics 20 22387375
2005 HIV-1 and the hijacking of dendritic cells: a tug of war. Springer seminars in immunopathology 20 15609004
2015 Newly designed break-apart and ASPL-TFE3 dual-fusion FISH assay are useful in diagnosing Xp11.2 translocation renal cell carcinoma and ASPL-TFE3 renal cell carcinoma: a STARD-compliant article. Medicine 19 25984679
2011 IFN-α/β and autophagy: tug-of-war between HCV and the host. Autophagy 19 21997372
2011 ASPS-1, a novel cell line manifesting key features of alveolar soft part sarcoma. Journal of pediatric hematology/oncology 18 21552147
2006 Solution structure and backbone dynamics of an N-terminal ubiquitin-like domain in the GLUT4-regulating protein, TUG. Protein science : a publication of the Protein Society 17 16501224
2020 Tug of War between Condensate Phases in a Minimal Macromolecular System. Journal of the American Chemical Society 16 32326697
2013 Targeted therapies in rare sarcomas: IMT, ASPS, SFT, PEComa, and CCS. Hematology/oncology clinics of North America 16 24093175
2008 Immunohistochemical discrimination between the ASPL-TFE3 fusion proteins of alveolar soft part sarcoma. Journal of pediatric hematology/oncology 16 18176180
2024 Patients with ASPSCR1-TFE3 fusion achieve better response to ICI based combination therapy among TFE3-rearranged renal cell carcinoma. Molecular cancer 15 38926757
2019 Cediranib phase-II study in children with metastatic alveolar soft-part sarcoma (ASPS). Pediatric blood & cancer 15 31502400
2001 Physiological and metabolic characteristics of elite tug of war athletes. British journal of sports medicine 15 11726473
2022 Tug-of-War between Internal and External Frictions and Viscosity Dependence of Rate in Biological Reactions. Physical review letters 14 35333093
2020 Stable tug-of-war between kinesin-1 and cytoplasmic dynein upon different ATP and roadblock concentrations. Journal of cell science 14 33257498
2019 Evolutionary history of burrowing asps (Lamprophiidae: Atractaspidinae) with emphasis on fang evolution and prey selection. PloS one 14 30995262
2016 Mutant p97 exhibits species-specific changes of its ATPase activity and compromises the UBXD9-mediated monomerisation of p97 hexamers. European journal of cell biology 14 27132113
2024 HTLV-1 Tax Tug-of-War: Cellular Senescence and Death or Cellular Transformation. Pathogens (Basel, Switzerland) 13 38276160
2023 TUG-891 inhibits neuronal endoplasmic reticulum stress and pyroptosis activation and protects neurons in a mouse model of intraventricular hemorrhage. Neural regeneration research 13 37056148
2023 PEComa with ASPSCR1::TFE3 fusion: expanding the molecular genetic spectrum of TFE3-rearranged PEComa with an emphasis on overlap with alveolar soft part sarcoma. Histopathology 13 37936565
2022 Ubiquitin-like processing of TUG proteins as a mechanism to regulate glucose uptake and energy metabolism in fat and muscle. Frontiers in endocrinology 13 36246906
2019 Docosahexaenoic acid and TUG-891 activate free fatty acid-4 receptor in bovine neutrophils. Veterinary immunology and immunopathology 13 30885306
2018 miRNA-mediated 'tug-of-war' model reveals ceRNA propensity of genes in cancers. Molecular oncology 13 29603582
2004 Establishment and characterization of a renal cell carcinoma cell line (FU-UR-1) with the reciprocal ASPL-TFE3 fusion transcript. Oncology reports 13 15138551
2000 APC and beta-catenin in alveolar soft part sarcoma (ASPS)--immunohistochemical and molecular genetic analysis. Pathology, research and practice 13 10834386

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