Affinage

TXNIP

Thioredoxin-interacting protein · UniProt Q9H3M7

Length
391 aa
Mass
43.7 kDa
Annotated
2026-06-10
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TXNIP is a redox-responsive α-arrestin scaffold that couples cellular oxidative and metabolic state to glucose handling, antioxidant capacity, inflammation, and cell-fate decisions (PMID:38329960, PMID:27437069). Its defining redox switch is the C247 disulfide bond with thioredoxin: this cysteine-dependent inhibition of thioredoxin oxidoreductase drives pro-oxidative, cytotoxic outcomes, and a cardiomyocyte C247S knock-in limits infarct size with reduced ROS (PMID:33652022). Rising ROS releases TXNIP from thioredoxin and redirects it through its C-terminal arrestin (C-ARR) domain and di-leucine endocytic motif onto class I glucose transporters GLUT1–4, which TXNIP internalizes (binding GLUT1 in a 1:1, PI(4,5)P2-dependent manner) and routes to lysosomal degradation, thereby restraining glucose uptake, glycolysis, the hexosamine and pentose phosphate pathways (PMID:34478732, PMID:38329960). TXNIP additionally acts as a tumor suppressor: it is required in vivo to prevent hepatocellular carcinoma, stabilizes p27(kip1) by blocking JAB1/CSN5-mediated nuclear export, promotes pVHL/CRM1-dependent nuclear export and degradation of HIF1α to suppress invasion, and restrains genome-wide Myc occupancy (PMID:16607285, PMID:15930262, PMID:18062927, PMID:36930677). Under oxidative stress TXNIP relocates and directly binds NLRP3 to activate the inflammasome and downstream caspase-1/IL-1β release, linking it to gout, glucocorticoid/corticosterone, and high-glucose inflammatory responses (PMID:30833078, PMID:31586460, PMID:36881408). It also engages signaling and stability partners including AMPK (driving mTORC1 inactivation, TFEB nuclear translocation, autophagy and fatty acid oxidation), STAT3, TAK1, and CHOP, the last stabilized by TXNIP to promote ER-stress apoptosis (PMID:33190588, PMID:33781783, PMID:38169654, PMID:37153733). TXNIP abundance is set by extensive transcriptional control via glucose-6-phosphate/MondoA-Mlx, ChREBP, FoxO1, the glucocorticoid receptor, and SIRT6/SIRT1-dependent histone deacetylation, and by post-translational stability control through ERK phosphorylation at Thr349, NEDD4L-mediated ubiquitination, and USP5-mediated deubiquitination (PMID:31993438, PMID:33748706, PMID:16301999, PMID:35562171, PMID:37742607, PMID:31320475, PMID:37153733, PMID:37534934).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2003 Medium

    Established an early function for TXNIP as a transcriptional co-repressor controlling cell-cycle exit, the first hint that it acts as a scaffold within nuclear complexes.

    Evidence Co-IP, reporter and cell-cycle assays linking TXNIP to PLZF/FAZF/HDAC1 repression of IL-3 receptor and cyclin A2

    PMID:12821938

    Open questions at the time
    • Direct DNA binding by TXNIP not demonstrated
    • Physiological relevance outside overexpression unclear
  2. 2005 High

    Defined how TXNIP restrains proliferation, by stabilizing the CDK inhibitor p27 through inhibition of JAB1-driven nuclear export, and showed it is required for NK cell maturation in vivo.

    Evidence Reciprocal co-IP and VDUP1-/- fibroblasts (p27); VDUP1-/- mice and flow cytometry (NK/CD122)

    PMID:15723808 PMID:15930262

    Open questions at the time
    • Whether p27 and NK phenotypes share a single molecular mechanism unresolved
    • Structural basis of JAB1 inhibition not defined
  3. 2006 High

    Demonstrated that TXNIP is a glucocorticoid-receptor primary response gene mediating apoptosis and a bona fide tumor suppressor required to prevent hepatocellular carcinoma in vivo.

    Evidence GRE promoter mutagenesis with gain/loss-of-function (Oncogene 2006); HcB-19 Txnip-mutant congenic mice with HCC cosegregation

    PMID:16301999 PMID:16607285

    Open questions at the time
    • Molecular effectors of TXNIP-driven apoptosis not defined in 2006
    • Link between tumor suppression and redox/metabolic functions not yet made
  4. 2007 Medium

    Connected TXNIP to hypoxia signaling and metastasis suppression by showing it enhances pVHL–HIF1α interaction and promotes CRM1-dependent nuclear export/degradation of HIF1α.

    Evidence Co-IP with pVHL, leptomycin B and NES-mutant export blockade, invasion/metastasis assays

    PMID:18062927

    Open questions at the time
    • Direct vs scaffolded contribution to HIF1α degradation not separated
    • In vivo metastasis dependence on this axis not genetically tested
  5. 2016 High

    Resolved how inflammatory cytokines tune TXNIP, with IL-1β repressing ChREBP-driven transcription and IFNγ raising TXNIP post-transcriptionally via IRE1α/miR-17.

    Evidence ChIP, promoter analysis, miR-17 gain/loss-of-function and IRE1α inhibition in INS-1 cells and primary islets

    PMID:26858253

    Open questions at the time
    • Integration of opposing cytokine inputs on net TXNIP level in vivo unclear
    • Whether miR-17 directly binds TXNIP 3'UTR shown only indirectly
  6. 2018 High

    Established TXNIP as a direct adaptor for GLUT1 internalization and identified two distinct upstream controls — ZFP36-mediated mRNA decay and Ras-mediated translational elongation repression — that lower TXNIP to boost glycolysis.

    Evidence Glycolytic driver screen, ZFP36 mRNA-decay and surface-GLUT1 assays, xenografts (Cell 2018); ribosome transit assays and mRNA/N-terminal mutants (MCB 2018)

    PMID:30037981 PMID:30197082

    Open questions at the time
    • Whether elongation control and decay act on the same TXNIP pool unknown
    • Endocytic machinery for GLUT1 internalization not yet structurally defined
  7. 2019 High

    Mapped multiple regulatory and effector arms: ERK-Thr349 phosphorylation triggering proteasomal degradation, direct NLRP3 binding to activate the inflammasome, AMPK–mTORC1–TFEB control of autophagy, and a redox-dependent BioID interactome.

    Evidence Thr349 mutagenesis/ubiquitination/ROS assays; TXNIP–NLRP3 co-IP and siRNA; TXNIP–AMPK co-IP with Txnip-KO and rapamycin rescue; BioID with C247S comparison

    PMID:27437069 PMID:30833078 PMID:31320475 PMID:31615975 PMID:33190588

    Open questions at the time
    • Whether single TXNIP molecule scaffolds multiple effectors or pools partition by condition unresolved
    • Direct NLRP3 binding interface not defined
  8. 2021 High

    Provided biophysical and genetic anchors for core mechanisms: reconstituted 1:1 PI(4,5)P2-dependent TXNIP–GLUT1 binding, and an in vivo C247S knock-in proving the thioredoxin disulfide drives pro-oxidative cardiac injury; expanded the partner set to STAT3 and nuclear HMW redox complexes.

    Evidence GLUT1 nanodiscs, ITC and EM (BBA Biomembranes); cardiac C247S knock-in with ROS/infarct readouts; STAT3 co-IP with KO/inhibitor; tandem-affinity proteomics (HSP90/HSP70/Prp31)

    PMID:31586460 PMID:31669268 PMID:33652022 PMID:33748706 PMID:33781783 PMID:34478732

    Open questions at the time
    • Stoichiometry and composition of nuclear HMW complexes not fully defined
    • STAT3 and TAK1 binding interfaces not mapped
  9. 2022 High

    Extended transcriptional control via SIRT6 histone deacetylation and identified context-specific roles in vascular calcification (BMP suppression), ferroptosis (downstream of PIAS3/TGF-β), and inflammasome regulation by SIRT1.

    Evidence SIRT6 ChIP with H3K9/H3K56ac; VSMC-specific Txnip KO with scRNA-seq and BMP inhibitor rescue; PIAS3–SMAD2/3 co-IP with TXNIP epistasis; SIRT1 gain/loss in lens epithelium

    PMID:35562171 PMID:36448450 PMID:36881408 PMID:37689128

    Open questions at the time
    • How TXNIP toggles between pro-survival and pro-death outputs not mechanistically unified
    • Direct molecular target through which TXNIP modulates BMP signaling unknown
  10. 2023 High

    Consolidated the ROS-gated TRX-to-GLUT shuttling model, defined the NEDD4L–USP5 ubiquitin/deubiquitin axis (and CHOP stabilization), added SIRT1/XBP1s promoter control, and revealed TXNIP restrains genome-wide Myc occupancy and shapes T-cell metabolism via MondoA.

    Evidence Domain-swap co-IP and metabolic flux (PLoS ONE); NEDD4L E3 screen and TXNIP–CHOP co-IP across NASH models; USP5 DUB screen; SIRT1 ChIP-qPCR/XBP1s; Myc ChIP-seq/RNA-seq in CRISPR-KO TNBC; MondoA-deletion T cells with SENP1 axis

    PMID:36930677 PMID:37153733 PMID:37534934 PMID:37742607 PMID:38329960 PMID:40846790

    Open questions at the time
    • Mechanism by which TXNIP loss permits Myc promoter/enhancer invasion is unresolved
    • Whether GLUT-binding and Myc-restraining functions are linked unknown
  11. 2024 Medium

    Added an endothelial protective role in which TXNIP suppresses TAK1 to preserve nitric oxide and limit liver sinusoidal capillarization.

    Evidence TXNIP–TAK1 co-IP, endothelial-specific Txnip KO, overexpression and TAK1 inhibitor rescue in LSECs

    PMID:38169654

    Open questions at the time
    • TAK1 binding interface and whether inhibition is direct vs scaffolded not defined
    • Single-lab co-IP without reciprocal structural validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unifying structural and biochemical model explaining how one redox-sensing α-arrestin partitions among thioredoxin, GLUT transporters, NLRP3, p27/JAB1, HIF1α, and Myc-restraining functions across cell types remains undefined.
  • No structure of full-length TXNIP bound to its major partners
  • Rules governing condition-specific complex selection not established
  • Direct DNA/chromatin relationship underlying Myc restraint unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0038024 cargo receptor activity 2 GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1640170 Cell Cycle 2 R-HSA-382551 Transport of small molecules 2 R-HSA-9612973 Autophagy 1
Partners
AMPKCHOPGLUT1JAB1NLRP3STAT3TAK1VHL
Complex memberships
NLRP3 inflammasomePLZF/FAZF/HDAC1 transcriptional repressor complexpVHL-HIF1α complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 VDUP1/TXNIP interacts with promyelocytic leukemia zinc-finger (PLZF), Fanconi anemia zinc-finger (FAZF), and histone deacetylase 1 (HDAC1), forming a transcriptional repressor complex that suppresses IL-3 receptor and cyclin A2 promoter activity, causing G0/G1 cell-cycle arrest. Co-immunoprecipitation, transfection/overexpression, reporter assays, cell-cycle analysis Oncogene Medium 12821938
2005 VDUP1/TXNIP interacts with JAB1 (CSN5) and blocks JAB1-mediated nuclear-to-cytoplasm translocation of p27(kip1), thereby stabilizing p27 and inhibiting cell proliferation. VDUP1-/- fibroblasts show reduced p27 and increased proliferation. Co-immunoprecipitation, VDUP1-/- fibroblast analysis, subcellular fractionation, cell proliferation assays Cancer research Medium 15930262
2005 VDUP1/TXNIP is required for NK cell development in vivo; VDUP1-/- mice show profound reduction in NK cell numbers and decreased NK activity, with reduced CD122 expression demonstrating that VDUP1 is required for CD122 expression and NK maturation. VDUP1-/- mouse model, flow cytometry, NK cytotoxicity assays Immunity High 15723808
2006 TXNIP is a glucocorticoid receptor primary response gene; a functional glucocorticoid response element (GRE) in the TXNIP promoter mediates dexamethasone-induced transcription, and TXNIP expression is sufficient to induce apoptosis in T lymphoma cells; RNAi knockdown of TXNIP inhibits glucocorticoid-induced apoptosis. Promoter deletion/mutation analysis, reporter assays, GFP-TXNIP overexpression, siRNA knockdown, Northern blot Oncogene High 16301999
2006 Txnip deficiency in mice (HcB-19 strain with spontaneous Txnip mutation) causes spontaneous hepatocellular carcinoma (~40% incidence), with increased alpha-fetoprotein and p53, demonstrating Txnip is a tumor suppressor gene required in vivo to prevent HCC. Recombinant inbred congenic mouse model, cosegregation analysis, histology, BrdU labeling, microarray Oncogene High 16607285
2007 VDUP1/TXNIP associates with the beta-domain of pVHL, enhances the pVHL–HIF1α interaction, and promotes CRM1-dependent nuclear export and degradation of HIF1α, suppressing cell invasiveness and tumor metastasis. Blocking VDUP1 nuclear export with leptomycin B or NES mutation inhibits HIF1α destabilization. Co-immunoprecipitation, nuclear export inhibition (leptomycin B), NES mutation, invasion/metastasis assays Biochimica et biophysica acta Medium 18062927
2016 IL-1β down-regulates TXNIP transcription via inhibition of carbohydrate response element binding protein (ChREBP) activity, while IFNγ increases TXNIP post-transcriptionally by inducing ER stress, activating IRE1α, and suppressing miR-17, a microRNA that targets TXNIP mRNA. miR-17 knockdown mimics IFNγ effects on TXNIP; miR-17 overexpression blunts IFNγ-induced TXNIP elevation. TXNIP promoter analysis, chromatin immunoprecipitation (ChIP), miR-17 overexpression/knockdown, IRE1α inhibition, primary islet studies The Journal of biological chemistry High 26858253
2018 Hyaluronan/ECM remodeling triggers receptor tyrosine kinase-mediated induction of the mRNA decay factor ZFP36, which targets TXNIP transcripts for degradation; acute TXNIP decline enriches GLUT1 at the plasma membrane because TXNIP normally promotes internalization (endocytosis) of GLUT1, thereby increasing glycolysis and cell migration. Unbiased glycolytic driver screen, hyaluronidase treatment of cells and xenografts, ZFP36 induction assays, GLUT1 surface trafficking analysis Cell High 30197082
2019 TXNIP directly interacts with and positively regulates phosphorylated AMPK (p-PRKAA), leading to inactivation of mTORC1 and nuclear translocation of TFEB, which promotes autophagy and fatty acid oxidation. Txnip-KO mice show impaired autophagy and fatty acid oxidation; rapamycin rescues this phenotype. Co-immunoprecipitation (TXNIP–AMPK), txnip-KO mice, rapamycin rescue, Atg7 silencing epistasis, nuclear TFEB localization Autophagy Medium 33190588
2019 ERK MAPK phosphorylates TXNIP at Thr349 within a PXTP motif in its C-terminal α-arrestin domain, triggering ubiquitination and proteasomal degradation of TXNIP, thereby releasing thioredoxin oxidoreductase activity; ERK inhibition augments intracellular ROS and S-nitrosothiols. ERK inhibitor pharmacology, site-directed mutagenesis of Thr349, ubiquitination assay, proteasome inhibition, ROS/S-nitrosothiol measurement The Journal of biological chemistry High 31320475
2019 TXNIP interacts with and shifts intracellularly from the nucleus to mitochondria under oxidative stress (MSU crystals); TXNIP directly binds NLRP3 under these conditions to activate the NLRP3 inflammasome and NF-κB signaling; antioxidants and TXNIP siRNA block this interaction and suppress inflammasome activation. Western blot, co-immunoprecipitation, TXNIP siRNA, subcellular fractionation, immunofluorescence localization Biochemical and biophysical research communications Medium 30833078
2019 TXNIP nucleoprotein complex: TXNIP forms redox-sensitive high molecular weight complexes (~1000–1300 kDa) in the nuclear fraction, partially dissolved by DTT; binding partners identified by tandem affinity purification and proteomics include HSP90, HSP70, and Prp31. Tandem affinity purification, proteomics (MS), native PAGE, DTT disruption, RNAse treatment Archives of biochemistry and biophysics Medium 31669268
2021 TXNIP interacts with GLUT1 in a 1:1 ratio, and this interaction requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2); TXNIP acts as an adaptor for GLUT1 in clathrin-mediated endocytosis to reduce glucose uptake, using its C-terminal arrestin domain and di-leucine endocytic motif. GLUT1 lipid nanodiscs, isothermal titration calorimetry (ITC), single-particle electron microscopy, PIP2 requirement tested Biochimica et biophysica acta. Biomembranes High 34478732
2021 Txnip C247S mutation abolishes disulfide bond formation with thioredoxin; cardiomyocyte-specific C247S knock-in mice have smaller infarct sizes after myocardial infarction with reduced ROS, demonstrating that Txnip's inhibition of thioredoxin via C247 disulfide is required for its pro-oxidative, cytotoxic effects in the heart. Site-directed mutagenesis, conditional knock-in mouse model, ROS measurement, infarct size quantification, RNA-seq Journal of molecular and cellular cardiology High 33652022
2021 Txnip directly binds STAT3 (confirmed by co-immunoprecipitation) and activates the STAT3 signaling pathway in renal tubular epithelial cells, thereby promoting a profibrotic response and accelerating renal aging; STAT3 inhibitor blocks TXNIP-mediated fibrosis. Co-immunoprecipitation, TXNIP overexpression/siRNA in tubular cells, TXNIP-KO mice, STAT3 inhibitor rescue Mechanisms of ageing and development Medium 33781783
2021 Corticosterone (chronic stress hormone) increases TXNIP protein and TXNIP–NLRP3 binding in microglia; CRISPR/Cas9 knockout of Txnip inhibits corticosterone-induced caspase-1 activity and IL-1β release, placing Txnip upstream of the NLRP3 inflammasome in corticosterone-induced neuroinflammation. Co-immunoprecipitation (TXNIP–NLRP3), CRISPR/Cas9 Txnip knockout, caspase-1 activity assay, ELISA for IL-1β Neurochemistry international Medium 31586460
2022 SIRT6 transcriptionally suppresses TXNIP by deacetylating H3K9ac and H3K56ac at the TXNIP locus (confirmed by ChIP), reducing TXNIP expression and thereby inhibiting microglial activation and promoting angiogenesis in cerebral ischemia. ChIP assay for SIRT6 occupancy and H3 deacetylation, SIRT6 overexpression, energy restriction diet model Cell death & disease Medium 35562171
2022 PIAS3 interacts with SMAD2/3 to activate TGF-β signaling, increasing TXNIP expression; TXNIP is required downstream of PIAS3 for ferroptotic cell death in hepatocellular carcinoma cells. TXNIP knockdown reduces PIAS3-overexpression-induced ferroptosis; forced TXNIP re-expression restores ferroptosis sensitivity. TMT-based proteomics, RNA-seq, co-immunoprecipitation (PIAS3–SMAD2/3), TXNIP knockdown/overexpression, ferroptosis assays Pharmacological research Medium 37689128
2022 SIRT1 acts as an upstream negative regulator of TXNIP/NLRP3 inflammasome activity in lens epithelial cells under high glucose; si-SIRT1 and LV-SIRT1 had inverse effects on NLRP3 inflammasome activation, and TXNIP knockdown inhibited NLRP3-induced IL-1β secretion. siRNA knockdown, lentiviral overexpression, NLRP3/TXNIP siRNA, Western blot, ROS measurement in HLECs and ex vivo rat lenses Investigative ophthalmology & visual science Medium 36881408
2022 TXNIP suppresses the osteochondrogenic transition of vascular smooth muscle cells (VSMCs) by inhibiting BMP signaling; smooth-muscle-specific Txnip knockout (Tagln-Cre; Txnip-flox) recapitulates increased atherosclerotic calcification and expanded osteochondrogenic clusters; BMP inhibitor K02288 abrogates the effect of TXNIP suppression on osteodifferentiation. Conditional VSMC-specific KO mice, single-cell RNA-seq, BMP inhibitor rescue, primary VSMC culture with TXNIP suppression Circulation research High 36448450
2023 NEDD4L is the E3 ubiquitin ligase responsible for TXNIP ubiquitination and proteasomal degradation in hepatocytes; decreased NEDD4L in NASH leads to impaired TXNIP ubiquitination and accumulation of TXNIP protein. TXNIP C-terminus associates with the α-helix domain N-terminus of CHOP, decreasing CHOP ubiquitination and stabilizing CHOP protein to drive ER stress-mediated apoptosis. Four NASH mouse models, E3 ligase screen, co-immunoprecipitation (TXNIP–CHOP), ubiquitination assay, adenovirus-mediated shRNA KD, gain/loss-of-function studies Theranostics High 37153733
2023 TXNIP shuttles between thioredoxin (TRX) and class I GLUTs (GLUT1–4) depending on intracellular ROS levels; elevated ROS shifts TXNIP from TRX to GLUTs via the C-terminal arrestin (C-ARR) domain; TXNIP then promotes lysosomal degradation of GLUTs through its di-leucine endocytic motif, reducing glucose uptake and suppressing glycolysis, hexosamine biosynthesis, and the pentose phosphate pathway. Co-immunoprecipitation, domain-swap/deletion mutants, ROS manipulation, GLUT surface expression, lysosomal inhibition, metabolic flux assays PloS one High 38329960
2023 USP5 deubiquitylase interacts with TXNIP (confirmed by co-immunoprecipitation) and stabilizes TXNIP by removing its ubiquitin modifications; USP5 knockdown reduces TXNIP levels, increases cell viability, and decreases inflammasome/apoptotic signaling in LPS-treated hepatocytes. Overexpression screen for deubiquitinase stabilizing TXNIP, co-immunoprecipitation, siRNA knockdown, ubiquitination assay Hepatology communications Medium 37534934
2023 SIRT1 deacetylates H3K9 at the TXNIP promoter (demonstrated by ChIP-qPCR) to repress TXNIP transcription; exenatide (exendin-4) upregulates SIRT1, which reduces TXNIP H3K9ac and decreases XBP1s recruitment to the TXNIP promoter, lowering TXNIP expression and protecting against diabetic kidney disease. ChIP-qPCR, whole-body and kidney-specific Sirt1 KO mice, exendin-4 treatment, XBP1s recruitment analysis Biomedicine & pharmacotherapy Medium 37742607
2019 Txnip BioID proximity labeling identified 31 interacting proteins; many interactions were disrupted by C247S mutation, demonstrating redox-dependent binding; hyperglycemia dynamically alters Txnip interactions, revealing that Txnip's pleiotropic functions are mediated through distinct, condition-specific protein complexes. BioID proximity labeling fused to Txnip in HEK293 cells, C247S mutant comparison, mass spectrometry Oxidative medicine and cellular longevity Medium 27437069
2018 Oncogenic Ras suppresses TXNIP protein synthesis by reducing ribosome transit rate along the TXNIP mRNA coding region (translational elongation); the N-terminal nascent TXNIP polypeptide is the target for Ras-dependent translational repression, independent of codon usage, mRNA secondary structure, or miRNAs. Ribosome profiling-based translational elongation assay, codon-randomized/optimized TXNIP mRNA variants, N-terminal truncation mutants Molecular and cellular biology High 30037981
2021 ChREBP and FoxO1 both up-regulate TxNIP expression in hepatocytes; genetic studies in mice with liver-specific deletion of ChREBP or FoxO1 show that both transcription factors are required for full TxNIP induction in response to glucose and fasting, respectively. Genetically modified mice (ChREBP and FoxO1 liver-specific models), gene expression analysis, db/db hyperglycemia model iScience Medium 33748706
2020 Glucose-6-phosphate (G6P) directly activates the transcription factor heterodimer MondoA/Mlx to upregulate TXNIP expression; EMSA and endogenous knockdown confirmed G6P (not glucose itself) as the activating metabolic intermediate. Mutational analysis of MondoA identified GKL139-141 residues as mediating G6P binding. EMSA (gel mobility shift), endogenous knockdown of MondoA, molecular docking, mutational analysis of MondoA binding residues Frontiers in molecular biosciences Medium 31993438
2023 MondoA-induced TXNIP transcription is activated by lactic acid via SENP1-dependent deSUMOylation of MondoA; in CD8+ T cells, the MondoA–TXNIP axis impairs TCR/CD28 signaling-induced activation by reducing glucose uptake and glycolysis; in Treg cells, TXNIP promotes immunosuppressive function. MondoA-deficient T cell models, glucose uptake assays, TCR activation assays, tumor immunotherapy models with anti-PD-1 combination Nature metabolism High 40846790
2024 TXNIP interacts with TAK1 (transforming growth factor β-activated kinase 1) in liver sinusoidal endothelial cells (LSECs) and suppresses the TAK1 pathway, thereby maintaining nitric oxide (NO) production; endothelial Txnip deletion leads to sinusoidal capillarization, reduced NO, increased pro-inflammatory cytokines, and aggravated alcohol-associated liver disease. Co-immunoprecipitation (TXNIP–TAK1), endothelial-specific Txnip KO mice, TXNIP overexpression in LSECs, TAK1 inhibitor rescue International journal of biological sciences Medium 38169654
2019 Elevated TXNIP in RPE cells undergoes downregulation under oxidative stress; TXNIP knockdown induces autophagic flux causing nuclear localization of p53, enhanced AMPK phosphorylation, disruption of tight junctions (via Src kinase phosphorylation), and increased HIF-1α leading to VEGF secretion from RPE cells. TXNIP siRNA knockdown in RPE cells, autophagy flux assay, subcellular localization of p53, Src kinase activity measurement, VEGF ELISA, co-culture angiogenesis assay Experimental & molecular medicine Medium 31615975
2023 TXNIP loss in MDA-MB-231 TNBC cells increases global Myc genome occupancy, allowing Myc to invade promoters and enhancers of additional target genes, expanding the Myc-dependent transcriptome without increasing Myc protein levels or Myc's intrinsic transcriptional activity. TXNIP null (CRISPR KO) MDA-MB-231 cells, ChIP-seq for Myc genome-wide occupancy, RNA-seq PLoS biology High 36930677

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Thioredoxin/Txnip: redoxisome, as a redox switch for the pathogenesis of diseases. Frontiers in immunology 310 24409188
2023 TXNIP: A key protein in the cellular stress response pathway and a potential therapeutic target. Experimental & molecular medicine 256 37394581
2003 VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression. Oncogene 234 12821938
2018 Extracellular Matrix Remodeling Regulates Glucose Metabolism through TXNIP Destabilization. Cell 216 30197082
2020 TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation. Autophagy 183 33190588
2017 TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook. Current drug targets 180 28137209
2012 Roles of thioredoxin binding protein (TXNIP) in oxidative stress, apoptosis and cancer. Mitochondrion 148 22750447
2018 Thioredoxin-Interacting Protein (TXNIP) in Cerebrovascular and Neurodegenerative Diseases: Regulation and Implication. Molecular neurobiology 140 29488135
2006 Hepatocellular carcinoma in Txnip-deficient mice. Oncogene 131 16607285
2005 VDUP1 is required for the development of natural killer cells. Immunity 123 15723808
2005 Tumor suppressor VDUP1 increases p27(kip1) stability by inhibiting JAB1. Cancer research 123 15930262
2020 Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases. International journal of molecular sciences 119 33302545
2013 Thioredoxin Interacting Protein (TXNIP) and Pathogenesis of Diabetic Retinopathy. Journal of clinical & experimental ophthalmology 110 24353900
2022 TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook. Oxidative medicine and cellular longevity 99 35450411
2007 Diverse functions of VDUP1 in cell proliferation, differentiation, and diseases. Cellular & molecular immunology 99 17976314
2006 Thioredoxin-interacting protein (txnip) is a glucocorticoid-regulated primary response gene involved in mediating glucocorticoid-induced apoptosis. Oncogene 99 16301999
2019 Thioredoxin-Interacting Protein (TXNIP) Associated NLRP3 Inflammasome Activation in Human Alzheimer's Disease Brain. Journal of Alzheimer's disease : JAD 97 30741672
2011 TXNIP (VDUP-1, TBP-2): a major redox regulator commonly suppressed in cancer by epigenetic mechanisms. The international journal of biochemistry & cell biology 96 21964212
2006 Structure of the Escherichia coli ThiS-ThiF complex, a key component of the sulfur transfer system in thiamin biosynthesis. Biochemistry 93 16388576
2017 ROS/TXNIP pathway contributes to thrombin induced NLRP3 inflammasome activation and cell apoptosis in microglia. Biochemical and biophysical research communications 92 28202418
2018 Diabetes pathogenic mechanisms and potential new therapies based upon a novel target called TXNIP. Current opinion in endocrinology, diabetes, and obesity 88 29356688
2020 TXNIP/TBP-2: A Master Regulator for Glucose Homeostasis. Antioxidants (Basel, Switzerland) 84 32824669
2022 Corilagin Restrains NLRP3 Inflammasome Activation and Pyroptosis through the ROS/TXNIP/NLRP3 Pathway to Prevent Inflammation. Oxidative medicine and cellular longevity 82 36299604
2007 TXNIP links redox circuitry to glucose control. Cell metabolism 72 17550776
2002 Vitamin D3 up-regulated protein 1 (VDUP1) expression in gastrointestinal cancer and its relation to stage of disease. Anticancer research 72 12553030
2021 TXNIP positively regulates the autophagy and apoptosis in the rat müller cell of diabetic retinopathy. Life sciences 69 33412212
2023 The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control. British journal of cancer 65 37794178
2019 Role of TXNIP/NLRP3 in sepsis-induced myocardial dysfunction. International journal of molecular medicine 63 31173172
2007 VDUP1 mediates nuclear export of HIF1alpha via CRM1-dependent pathway. Biochimica et biophysica acta 62 18062927
2006 Vitamin D3 upregulated protein 1 (VDUP1) is a regulator for redox signaling and stress-mediated diseases. The Journal of dermatology 61 17040494
2015 Foam cell-derived 4-hydroxynonenal induces endothelial cell senescence in a TXNIP-dependent manner. Journal of cellular and molecular medicine 56 25754218
2016 Cytokines Regulate β-Cell Thioredoxin-interacting Protein (TXNIP) via Distinct Mechanisms and Pathways. The Journal of biological chemistry 54 26858253
2019 Oxidative stress-mediated TXNIP loss causes RPE dysfunction. Experimental & molecular medicine 53 31615975
2023 SIRT1 Inhibits High Glucose-Induced TXNIP/NLRP3 Inflammasome Activation and Cataract Formation. Investigative ophthalmology & visual science 52 36881408
2005 Structural analysis of Escherichia coli ThiF. Journal of molecular biology 52 15896804
2022 AGE-TXNIP axis drives inflammation in Alzheimer's by targeting Aβ to mitochondria in microglia. Cell death & disease 51 35379773
2019 UHRF1 promotes renal cell carcinoma progression through epigenetic regulation of TXNIP. Oncogene 50 31043707
2021 The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target. International journal of molecular sciences 49 33567593
2001 Cloning, genetic characterization, and chromosomal mapping of the mouse VDUP1 gene. Gene 48 11376942
2022 TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis. Circulation research 44 36448450
2023 Exercise-induced irisin improves follicular dysfunction by inhibiting IRE1α-TXNIP/ROS-NLRP3 pathway in PCOS. Journal of ovarian research 43 37525261
2022 Energy restriction induced SIRT6 inhibits microglia activation and promotes angiogenesis in cerebral ischemia via transcriptional inhibition of TXNIP. Cell death & disease 42 35562171
2022 TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients. Medicine and pharmacy reports 42 36060506
2019 TXNIP-mediated nuclear factor-κB signaling pathway and intracellular shifting of TXNIP in uric acid-induced NLRP3 inflammasome. Biochemical and biophysical research communications 42 30833078
2001 Rapid induction and Ca(2+) influx-mediated suppression of vitamin D3 up-regulated protein 1 (VDUP1) mRNA in cerebellar granule neurons undergoing apoptosis. Journal of neurochemistry 40 11579135
2021 Thioredoxin-interacting protein (TXNIP) as a target for Alzheimer's disease: flavonoids and phenols. Inflammopharmacology 37 34350508
2018 Metabolic Syndrome, Brain Insulin Resistance, and Alzheimer's Disease: Thioredoxin Interacting Protein (TXNIP) and Inflammasome as Core Amplifiers. Journal of Alzheimer's disease : JAD 36 30372683
2024 Coptisine alleviates colitis through modulating gut microbiota and inhibiting TXNIP/NLRP3 inflammasome. Journal of ethnopharmacology 35 39117021
2017 Mapping Txnip: Key connexions in progression of diabetic nephropathy. Pharmacological reports : PR 34 29684849
2022 Calycosin modulates NLRP3 and TXNIP-mediated pyroptotic signaling and attenuates diabetic nephropathy progression in diabetic rats; An insight. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 33 36271546
2019 Txnip mediates glucocorticoid-activated NLRP3 inflammatory signaling in mouse microglia. Neurochemistry international 31 31586460
2023 PIAS3 promotes ferroptosis by regulating TXNIP via TGF-β signaling pathway in hepatocellular carcinoma. Pharmacological research 30 37689128
2003 Vitamin D(3) up-regulating protein 1 (VDUP1) antisense DNA regulates tumorigenicity and melanogenesis of murine melanoma cells via regulating the expression of fas ligand and reactive oxygen species. Immunology letters 29 12706526
2019 Sodium butyrate-activated TRAF6-TXNIP pathway affects A549 cells proliferation and migration. Cancer medicine 28 31578830
2021 HOXA9-induced chemerin signals through CMKLR1/AMPK/TXNIP/NLRP3 pathway to induce pyroptosis of trophoblasts and aggravate preeclampsia. Experimental cell research 27 34461109
2024 TXNIP-mediated crosstalk between oxidative stress and glucose metabolism. PloS one 24 38329960
2023 Memantine mitigates ROS/TXNIP/NLRP3 signaling and protects against mouse diabetic retinopathy: Histopathologic, ultrastructural and bioinformatic studies. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 37116352
2022 TXNIP Links Anticipatory Unfolded Protein Response to Estrogen Reprogramming Glucose Metabolism in Breast Cancer Cells. Endocrinology 23 34614512
2021 Role and mechanism of TXNIP in ageing-related renal fibrosis. Mechanisms of ageing and development 22 33781783
2010 Differential roles of Annexin A1 (ANXA1/lipocortin-1/lipomodulin) and thioredoxin binding protein-2 (TBP-2/VDUP1/TXNIP) in glucocorticoid signaling of HTLV-I-transformed T cells. Immunology letters 22 20398702
2010 Thioredoxin-binding protein-2 (TBP-2/VDUP1/TXNIP) regulates T-cell sensitivity to glucocorticoid during HTLV-I-induced transformation. Leukemia 22 21151022
2023 PIN1 and PIN4 inhibition via parvulin impeders Juglone, PiB, ATRA, 6,7,4'-THIF, KPT6566, and EGCG thwarted hepatitis B virus replication. Frontiers in microbiology 21 36760500
2021 Expression of TXNIP is associated with angiogenesis and postoperative relapse of conventional renal cell carcinoma. Scientific reports 21 34433833
2023 A novel NEDD4L-TXNIP-CHOP axis in the pathogenesis of nonalcoholic steatohepatitis. Theranostics 20 37153733
2022 Celastrol targets the ChREBP-TXNIP axis to ameliorates type 2 diabetes mellitus. Phytomedicine : international journal of phytotherapy and phytopharmacology 20 36603341
2021 Dual regulation of TxNIP by ChREBP and FoxO1 in liver. iScience 20 33748706
2025 Targeting MondoA-TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment. Nature metabolism 19 40846790
2024 The ROS/TXNIP/NLRP3 pathway mediates LPS-induced microglial inflammatory response. Cytokine 19 38896955
2023 TXNIP activates NLRP3/IL-1β and participate in inflammatory response and oxidative stress to promote deep venous thrombosis. Experimental biology and medicine (Maywood, N.J.) 18 37749991
2024 piR112710 attenuates diabetic cardiomyopathy through inhibiting Txnip/NLRP3-mediated pyroptosis in db/db mice. Cellular signalling 17 39102928
2022 Ceramide induces pyroptosis through TXNIP/NLRP3/GSDMD pathway in HUVECs. BMC molecular and cell biology 17 36517743
2024 TXNIP in liver sinusoidal endothelial cells ameliorates alcohol-associated liver disease via nitric oxide production. International journal of biological sciences 16 38169654
2022 Overview on Thioredoxin-Interacting Protein (TXNIP): A Potential Target for Diabetes Intervention. Current drug targets 16 35240955
2005 VDUP1: a potential mediator of expansion-induced lung growth and epithelial cell differentiation in the ovine fetus. American journal of physiology. Lung cellular and molecular physiology 16 16143587
2021 Txnip C247S mutation protects the heart against acute myocardial infarction. Journal of molecular and cellular cardiology 15 33652022
2024 PTBP1 knockdown impairs autophagy flux and inhibits gastric cancer progression through TXNIP-mediated oxidative stress. Cellular & molecular biology letters 14 39153986
2021 TXNIP interaction with GLUT1 depends on PI(4,5)P2. Biochimica et biophysica acta. Biomembranes 14 34478732
2021 DNA Methylation of TXNIP Independently Associated with Inflammation and Diabetes Mellitus in Twins. Twin research and human genetics : the official journal of the International Society for Twin Studies 14 34726138
2016 Identification of Redox and Glucose-Dependent Txnip Protein Interactions. Oxidative medicine and cellular longevity 14 27437069
2025 FOXO regulation of TXNIP induces ferroptosis in satellite cells by inhibiting glutathione metabolism, promoting Sarcopenia. Cellular and molecular life sciences : CMLS 13 39982519
2023 DNMT1 regulates miR-20a/TXNIP-mediated pyroptosis of retinal pigment epithelial cells through DNA methylation. Molecular and cellular endocrinology 13 37506869
2023 USP5 promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein. Hepatology communications 13 37534934
2018 Ras Suppresses TXNIP Expression by Restricting Ribosome Translocation. Molecular and cellular biology 13 30037981
2009 Expression and regulation of vitamin D3 upregulated protein 1 (VDUP1) is conserved in mammalian and insect brain. The Journal of comparative neurology 13 19824090
2023 High TXNIP expression accelerates the migration and invasion of the GDM placenta trophoblast. BMC pregnancy and childbirth 12 37038114
2022 Galectin-3 induces vascular smooth muscle cells calcification via AMPK/TXNIP pathway. Aging 12 35771146
2023 TXNIP loss expands Myc-dependent transcriptional programs by increasing Myc genomic binding. PLoS biology 11 36930677
2023 Narirutin Attenuates Cerebral Ischemia-Reperfusion Injury by Suppressing the TXNIP/NLRP3 Pathway. Neurochemical research 11 38047987
2021 Antidiabetic effects of quercetin and liraglutide combination through modulation of TXNIP/IRS-1/PI3K pathway. Cell biochemistry and function 11 34855213
2020 The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma. Dermatology (Basel, Switzerland) 11 32799209
2019 ERK-dependent proteasome degradation of Txnip regulates thioredoxin oxidoreductase activity. The Journal of biological chemistry 11 31320475
2023 Depletion of pyruvate kinase (PK) activity causes glycolytic intermediate imbalances and reveals a PK-TXNIP regulatory axis. Molecular metabolism 10 37290673
2023 SIRT1-dependent deacetylation of Txnip H3K9ac is critical for exenatide-improved diabetic kidney disease. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 10 37742607
2022 Celastrol inhibits TXNIP expression to protect pancreatic β cells in diabetic mice. Phytomedicine : international journal of phytotherapy and phytopharmacology 10 35820305
2022 Targeted Induction of Endogenous VDUP1 by Small Activating RNA Inhibits the Growth of Lung Cancer Cells. International journal of molecular sciences 10 35887091
2022 MicroRNA-25-5p negatively regulates TXNIP expression and relieves inflammatory responses of brain induced by lipopolysaccharide. Scientific reports 10 36289253
2020 Glucose-6-Phosphate Upregulates Txnip Expression by Interacting With MondoA. Frontiers in molecular biosciences 10 31993438
2019 Thioredoxin interacting protein (Txnip) forms redox sensitive high molecular weight nucleoprotein complexes. Archives of biochemistry and biophysics 10 31669268
2023 Effects of evodiamine on ROS/TXNIP/NLRP3 pathway against gouty arthritis. Naunyn-Schmiedeberg's archives of pharmacology 9 37555854
2021 YAP/miR-524-5p axis negatively regulates TXNIP expression to promote chondrosarcoma cell growth. Biochemical and biophysical research communications 9 34968780

Missed literature

Know a paper Affinage missed for TXNIP? Flag it for the maintainers and the community.

No submissions yet.