Affinage

TXNIP

Thioredoxin-interacting protein · UniProt Q9H3M7

Length
391 aa
Mass
43.7 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TXNIP is a multifunctional α-arrestin scaffold protein that serves as a central integrator of cellular redox sensing, glucose metabolism, and stress-induced signaling. It directly binds and inhibits thioredoxin (TRX) via a disulfide bond requiring TRX Cys32/Cys35 and TXNIP Cys247, and this interaction reciprocally stabilizes TXNIP protein against proteasomal degradation (PMID:10814541, PMID:21705327); TXNIP also suppresses glucose uptake by promoting GLUT1 internalization and lysosomal degradation through its C-terminal arrestin domain and a di-leucine endocytic motif (PMID:38329960, PMID:30197082). Under ER/oxidative stress, TXNIP shuttles from the nucleus to mitochondria where it displaces ASK1 from Trx2 to trigger apoptosis and activates the NLRP3 inflammasome—an interaction enhanced by O-GlcNAcylation—while also regulating autophagy via AMPK activation and mTORC1 inhibition (PMID:35994650, PMID:31164864, PMID:33190588). TXNIP expression is transcriptionally driven by glucose through the MondoA/ChREBP–ChoRE axis and by glucocorticoid receptor signaling, epigenetically tuned by histone acetylation at its promoter, and post-translationally controlled by NEDD4L-mediated ubiquitination and USP5-mediated deubiquitination (PMID:19246513, PMID:16301999, PMID:26806835, PMID:37153733, PMID:37534934).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    The foundational question of whether TXNIP directly binds thioredoxin was resolved: TXNIP interacts with TRX through a region spanning aa 155–225, requiring the TRX active-site cysteines Cys32/Cys35, establishing TXNIP as the first endogenous TRX inhibitor.

    Evidence Yeast two-hybrid screen with deletion and cysteine-to-serine point mutagenesis

    PMID:10814541

    Open questions at the time
    • TXNIP's own cysteine residue mediating the disulfide bond was not yet identified
    • functional consequences of TRX inhibition in vivo were not addressed
  2. 2005 High

    Beyond redox regulation, TXNIP was shown to control cell proliferation by binding JAB1 and preventing JAB1-mediated cytoplasmic translocation and degradation of the CDK inhibitor p27(kip1), revealing a TRX-independent tumor-suppressive mechanism.

    Evidence Reciprocal Co-IP, VDUP1−/− fibroblast phenotyping, nuclear export rescue assay

    PMID:15930262

    Open questions at the time
    • Whether the JAB1 interaction depends on the same domain as TRX binding was unknown
    • relevance to in vivo tumor suppression was not tested
  3. 2006 High

    Two parallel advances defined TXNIP's role as a nuclear scaffold and its transcriptional regulation: TXNIP was found to bridge pVHL and HIF1α for CRM1-dependent nuclear export and degradation of HIF1α, and glucocorticoid receptor was identified as a direct transcriptional inducer of TXNIP through a GRE in its promoter, with TXNIP mediating GR-induced apoptosis.

    Evidence Co-IP with NES mutagenesis and leptomycin B rescue for pVHL–HIF1α axis; promoter deletion/mutation reporter assays and RNAi rescue for GR–apoptosis axis

    PMID:16301999 PMID:18062927

    Open questions at the time
    • Whether the pVHL and TRX interactions are mutually exclusive was not determined
    • identity of TXNIP's NES and its regulation were not fully mapped
  4. 2009 Medium

    The glucose-sensing transcriptional mechanism was elucidated: MondoA and Mlx were identified as the transcription factors that induce TXNIP through a carbohydrate response element (ChoRE) in the promoter, explaining how TXNIP expression tracks cellular glucose availability.

    Evidence Promoter reporter assays with MondoA/ChREBP overexpression and adenosine analog treatment

    PMID:19246513

    Open questions at the time
    • Cell-type specificity of MondoA versus ChREBP contribution was unresolved
    • chromatin-level confirmation (e.g., ChIP) was not performed in this study
  5. 2011 High

    The reciprocal stabilization between TXNIP and TRX was demonstrated: TRX binding protects TXNIP from proteasomal degradation via PPXY-motif-dependent E3 ligase recruitment, and TXNIP Cys247 was identified as essential for the disulfide bond; separately, hypothalamic TXNIP was shown to regulate systemic metabolism, as MBH-specific knockdown prevented diet-induced obesity.

    Evidence C247S and PPXY mutagenesis with proteasome inhibitor and adipogenesis assays; lentiviral shRNA in mouse MBH with metabolic phenotyping

    PMID:21508227 PMID:21705327

    Open questions at the time
    • The specific E3 ligase recognizing the PPXY motifs was not identified at this stage
    • the TRX-independent metabolic functions in neurons were not mechanistically dissected
  6. 2012 High

    Cell-type-specific genetic manipulation in Agrp neurons demonstrated that TXNIP bidirectionally controls energy expenditure and diet-induced obesity through central leptin sensitivity, independent of food intake.

    Evidence Agrp-Ires-Cre × Txnip-flox conditional KO and lentiviral gain-of-function with metabolic cage phenotyping

    PMID:22815502

    Open questions at the time
    • Direct molecular target of TXNIP in Agrp neurons (beyond leptin sensitivity) was not defined
    • whether TRX inhibition or GLUT regulation mediates the neuronal effect was unknown
  7. 2015 Medium

    Upstream signaling inputs to TXNIP were expanded: CD36 was placed upstream of NF-κB-dependent TXNIP induction in β-cells during ceramide stress, and PPARδ was identified as a mediator of 4-HNE-induced TXNIP upregulation driving endothelial senescence.

    Evidence SSO pharmacological blockade with NF-κB inhibition epistasis in INS-1 cells; co-culture transwell system with PPARδ modulation and senescence assays

    PMID:25754218 PMID:26297980

    Open questions at the time
    • Direct promoter binding by NF-κB at the TXNIP locus was not confirmed by ChIP
    • whether PPARδ directly binds the TXNIP promoter or acts indirectly was unclear
  8. 2016 High

    Three mechanistic dimensions were clarified: (1) glucose-driven histone acetylation (H3K9ac, H3K4me3) at the TXNIP promoter was established as an epigenetic mechanism of TXNIP induction; (2) the C-terminal arrestin domain and di-leucine motif were mapped as the structural basis for GLUT1 endocytosis and lysosomal degradation; (3) BioID proximity labeling revealed a redox-dependent interactome of 31 partners altered by C247S mutation and hyperglycemia.

    Evidence ChIP with p300 inhibitor C646 in diabetic kidneys; C-ARR domain deletion and LL motif mutagenesis with glucose uptake assays; BioID-MS with C247S comparison

    PMID:26806835 PMID:27437069 PMID:38329960

    Open questions at the time
    • Which specific histone acetyltransferases other than p300 contribute was not resolved
    • whether the 31 BioID-identified interactors represent direct or proximity-based associations was unclear
  9. 2018 High

    Two modes of TXNIP regulation were defined: ZFP36 was identified as an mRNA decay factor that degrades TXNIP transcripts downstream of receptor tyrosine kinase signaling to permit GLUT1 surface enrichment and glycolysis; separately, Ras was shown to suppress TXNIP at the translational elongation level through a mechanism dependent on the N-terminal nascent polypeptide.

    Evidence Unbiased glycolytic driver screen with ZFP36 mRNA decay assays and GLUT1 surface quantification; polysome profiling and ribosome transit assays with codon optimization mutagenesis

    PMID:30037981 PMID:30197082

    Open questions at the time
    • The RNA-binding protein or ribosome factor mediating Ras-dependent translational stalling was not identified
    • whether ZFP36 and Ras pathways converge was not tested
  10. 2019 High

    O-GlcNAcylation was identified as a post-translational modification that stabilizes the TXNIP–NLRP3 interaction in pancreatic β-cells, with UHRF1/HDAC1-mediated H3K9 deacetylation separately established as an epigenetic silencing mechanism for TXNIP in renal cell carcinoma.

    Evidence O-GlcNAc immunoprecipitation with OGT/OGA manipulation and IL-1β ELISA in human islets; ChIP for HDAC1 at TXNIP promoter with epistasis knockdown and xenograft validation

    PMID:31043707 PMID:31164864

    Open questions at the time
    • The specific O-GlcNAcylation sites on TXNIP were not mapped
    • whether UHRF1-mediated silencing operates in non-cancer contexts was not tested
  11. 2020 High

    TXNIP was shown to directly bind and activate AMPKα, leading to mTORC1 inactivation and TFEB nuclear translocation to promote autophagy and fatty acid oxidation in hepatocytes; Txnip-KO mice developed exacerbated steatohepatitis.

    Evidence Co-IP of TXNIP–PRKAA, Txnip-KO mice on MCD diet, rapamycin rescue, Atg7 siRNA epistasis

    PMID:33190588

    Open questions at the time
    • Whether TXNIP activates AMPK through allosteric binding or by affecting upstream kinases was not resolved
    • the interplay between TRX inhibition and AMPK activation was not dissected
  12. 2021 High

    Multiple new regulatory connections were established: AAV-delivered TXNIP C247S (TRX-binding-deficient) rescued cone photoreceptors in retinitis pigmentosa models via Ldhb-dependent lactate catabolism; TXNIP was found to bind STAT3 and promote renal fibrosis/senescence; TRAF6 was identified as a ubiquitin ligase for TXNIP via its PPXY motifs; and MondoA (not ChREBP) was confirmed as the cell-type-specific transcriptional inducer in cervical cancer.

    Evidence AAV gene delivery with C247S allele and Ldhb epistasis in RP mice; Co-IP of TXNIP–STAT3 with Txnip-KO mice; Co-IP and ubiquitylation assays with TRAF6 C70A mutant; MondoA reporter assays and siRNA epistasis

    PMID:31578830 PMID:31782782 PMID:33781783 PMID:33847261

    Open questions at the time
    • Whether TXNIP's lactate-catabolism-promoting activity operates in tissues other than photoreceptors was unknown
    • the STAT3 binding interface on TXNIP was not mapped
    • whether TRAF6 is the physiological E3 ligase in metabolic tissues was not confirmed
  13. 2022 High

    The stress-dependent subcellular trafficking of TXNIP was defined: TXNIP resides in the nucleus basally but shuttles to mitochondria under oxidative/ER stress (CHOP-dependent), where it displaces ASK1 from Trx2 to trigger apoptosis and engages NLRP3 for inflammasome activation; SIRT6 was identified as a TXNIP transcriptional repressor via H3K9ac/H3K56ac deacetylation; and VSMC-specific Txnip deletion increased atherosclerotic calcification through de-repressed BMP signaling.

    Evidence Subcellular fractionation with Chop−/− and Txnip−/− mice and 68Ga-Galuminox imaging; ChIP for H3K9ac/H3K56ac with SIRT6 overexpression; Tagln-Cre Txnipflox/flox mice with scRNA-seq and BMP inhibitor epistasis

    PMID:35562171 PMID:35994650 PMID:36448450

    Open questions at the time
    • The signal or kinase mediating CHOP-dependent TXNIP phosphorylation/mitochondrial import was not identified
    • whether SIRT6 regulation is tissue-specific or generalizable was not addressed
  14. 2023 High

    The E3 ligase NEDD4L was identified as the primary ubiquitin ligase targeting TXNIP for degradation in NASH; accumulated TXNIP reciprocally stabilizes CHOP by binding its N-terminal α-helix domain and reducing CHOP ubiquitination. Separately, USP5 was identified as a deubiquitylase that stabilizes TXNIP to promote NLRP3 inflammasome activation.

    Evidence Co-IP with TXNIP–CHOP domain mapping and ubiquitination assays in four NASH mouse models; deubiquitylase screen with Co-IP and epistasis rescue

    PMID:37153733 PMID:37534934

    Open questions at the time
    • Whether NEDD4L and USP5 compete for TXNIP regulation in the same cellular context was not tested
    • the ubiquitin chain type on TXNIP was not fully characterized
  15. 2025 High

    The MondoA–TXNIP axis was shown to operate as a metabolic checkpoint in tumor immunity: lactic acid activates MondoA via SENP1-mediated de-SUMOylation, inducing TXNIP in CD8+ T cells to restrict glucose uptake and impair TCR/CD28 signaling, while the same axis maintains Treg immunosuppressive function.

    Evidence MondoA conditional KO mice in immune subsets, SENP1 manipulation, glucose uptake and TCR signaling assays, tumor models with anti-PD-1

    PMID:40846790

    Open questions at the time
    • Whether direct TXNIP–GLUT1 interaction mediates T cell glucose restriction or an alternative mechanism operates was not confirmed
    • the TXNIP O-GlcNAcylation and inflammasome axis in the tumor immune microenvironment was not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of TXNIP's multi-domain scaffold interactions (no crystal or cryo-EM structure of TXNIP in complex with any partner), the identity of the kinase or signal mediating CHOP-dependent TXNIP phosphorylation and mitochondrial import, and how competing post-translational modifications (O-GlcNAcylation, ubiquitination by NEDD4L/TRAF6, deubiquitination by USP5, TRX-mediated stabilization) are coordinately regulated in different tissues.
  • No structural model of TXNIP or its complexes exists
  • The specific phosphorylation sites driving mitochondrial translocation are unmapped
  • Tissue-specific hierarchy of TXNIP's E3 ligases (NEDD4L vs TRAF6) and deubiquitylases is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 2 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2
Partners
GLUT1JAB1NEDD4LNLRP3PRKAA1TXNTXN2USP5
Complex memberships
NLRP3 inflammasome

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 TXNIP (VDUP1) directly binds to thioredoxin (TRX) via a region spanning amino acids 155–225 of TXNIP; interaction requires Cys32 and Cys35 of TRX and is abolished by mutation of these cysteines to serines, establishing TXNIP as an endogenous inhibitor of TRX. Yeast two-hybrid screen with HeLa cDNA library, deletion and point-mutation mapping Biochemical and biophysical research communications High 10814541
2005 TXNIP (VDUP1) interacts with JAB1 and blocks JAB1-mediated cytoplasmic translocation of p27(kip1), thereby stabilizing p27(kip1) protein levels and inhibiting cell proliferation; VDUP1−/− fibroblasts proliferate faster with reduced p27(kip1). Co-immunoprecipitation, KO fibroblast phenotyping, nuclear export rescue assay, AP-1 reporter assay Cancer research High 15930262
2006 TXNIP (VDUP1) associates with the β-domain of pVHL and enhances pVHL–HIF1α interaction, mediating nuclear export and degradation of HIF1α via CRM1-dependent pathway; blocking TXNIP nuclear export signal or using leptomycin B prevents HIF1α destabilization and restores cell invasiveness. Co-immunoprecipitation, nuclear export signal mutation, leptomycin B treatment, invasion assays, tumor xenograft Biochimica et biophysica acta High 18062927
2006 Glucocorticoid receptor (GR) transcriptionally induces TXNIP expression through a functional glucocorticoid response element (GRE) in the TXNIP promoter; GFP-TXNIP overexpression is sufficient to induce apoptosis, and siRNA knockdown of TXNIP inhibits dexamethasone-induced apoptosis in T-cell lymphoma cells. Promoter deletion/mutation analysis, reporter assays, RU486 blockade, RNA interference, GFP-TXNIP overexpression with apoptosis readout Oncogene High 16301999
2011 Thioredoxin binding to TXNIP stabilizes TXNIP protein by protecting it from proteasomal degradation; a Txnip C247S mutant that cannot bind thioredoxin is degraded more rapidly. TXNIP inhibits adipogenesis directly, and this activity requires its PPXY motifs that mediate E3 ubiquitin ligase binding; adipogenic stimulants promote Txnip-thioredoxin dissociation leading to Txnip degradation and permitting adipocyte differentiation. In vitro differentiation assays, proteasome inhibitor studies, mutagenesis of C247S and PPXY motifs, thioredoxin overexpression The Journal of biological chemistry High 21705327
2009 TXNIP transcription is induced by adenosine-containing molecules through the carbohydrate response element (ChoRE) in the TXNIP promoter in a glucose-dependent manner; MondoA and Max-like protein X (Mlx) are the transcription factors conveying these signals to the TXNIP promoter. Promoter reporter assays, ChREBP/MondoA overexpression, adenosine analog treatments Molecular endocrinology Medium 19246513
2011 TXNIP is expressed in nutrient-sensing neurons of the mediobasal hypothalamus (MBH); downregulation of MBH TXNIP by lentiviral shRNA prevents diet-induced obesity and insulin resistance, regulating adipose tissue metabolism and glucose homeostasis. Lentiviral shRNA knockdown in mice, stereotaxic injection, metabolic phenotyping (glucose tolerance, body weight, adiposity) The Journal of neuroscience Medium 21508227
2012 TXNIP overexpression in Agrp neurons increases diet-induced obesity and adiposity by decreasing energy expenditure without affecting food intake; Agrp-specific TXNIP deletion protects against diet-induced obesity and improves glucose tolerance, acting through central leptin sensitivity and regulation of lipolysis. Agrp-Ires-cre × Txnip-flox conditional KO and lentiviral gain-of-function, metabolic cage phenotyping, glucose clamps The Journal of neuroscience High 22815502
2018 TXNIP promotes internalization and lysosomal degradation of GLUT1, reducing glucose uptake at the plasma membrane; ZFP36 (an mRNA decay factor) induced downstream of hyaluronidase/receptor tyrosine kinase signaling targets TXNIP transcripts for degradation, thereby enriching GLUT1 at the plasma membrane and increasing glycolysis. Unbiased glycolytic driver screen, hyaluronidase treatment of cells and xenografts, ZFP36 mRNA decay assay, GLUT1 surface localization (flow cytometry/imaging), glucose uptake assay Cell High 30197082
2016 TXNIP interacts with class I GLUTs through its C-terminal arrestin (C-ARR) domain; upon intracellular ROS increase, TXNIP robustly binds GLUTs, promoting their surface downregulation and lysosomal degradation via a di-leucine (LL) endocytic motif, thereby suppressing glycolysis, hexosamine biosynthesis, and the pentose phosphate pathway. Co-immunoprecipitation, domain-deletion mapping (C-ARR), mutagenesis of LL endocytic motif, glucose uptake assays, lysosomal degradation assays, metabolic flux analysis PloS one High 38329960
2019 Under ER stress, TXNIP is phosphorylated/activated by CHOP upregulation and shuttles from the nucleus to mitochondria, where it binds mitochondrial Trx2; this releases ASK1 to induce mitochondria-dependent apoptosis and liberates TXNIP to associate with mitochondrial NLRP3 to activate the inflammasome. CHOP deletion blocks TXNIP mitochondrial translocation and suppresses both pathways. Chop−/− and Txnip−/− mice, 68Ga-Galuminox mitochondrial ROS imaging, fractionation, Co-IP, nephrotic syndrome genetic model Proceedings of the National Academy of Sciences of the United States of America High 35994650
2020 TXNIP directly interacts with PRKAA (AMPKα) to positively regulate its activity, leading to MTORC1 inactivation and nuclear translocation of TFEB, thereby promoting autophagy and fatty acid oxidation in hepatocytes; Txnip-KO mice show impaired autophagy and exacerbated steatohepatitis. Co-immunoprecipitation, Txnip-KO mice fed MCD diet, rapamycin rescue, Atg7 siRNA epistasis, TFEB nuclear translocation imaging Autophagy High 33190588
2018 Ras suppresses TXNIP protein synthesis by reducing the rate of ribosome translocation through the TXNIP coding sequence; codon randomization/optimization did not relieve repression, but the N-terminal nascent TXNIP polypeptide is the target for Ras-dependent translational repression. Polysome profiling, ribosome transit assay, codon randomization/optimization mutagenesis, Ras activation system Molecular and cellular biology High 30037981
2019 O-GlcNAcylation of TXNIP by OGT in response to high glucose promotes the interaction of TXNIP with NLRP3 in pancreatic β-cells; reducing TXNIP O-GlcNAcylation via OGA overexpression destabilizes this interaction and reduces inflammasome-dependent IL-1β cleavage. O-GlcNAc immunoprecipitation, OGT/OGA overexpression and inhibitor studies, Co-IP of TXNIP–NLRP3, IL-1β ELISA in human and rat islets Frontiers in endocrinology High 31164864
2015 CD36 scavenger receptor mediates ceramide-induced NF-κB activation, which in turn upregulates TXNIP expression and NF-κB-TXNIP signaling in pancreatic β-cells; SSO (irreversible CD36 inhibitor) blocks ceramide-induced TXNIP induction and apoptosis, placing CD36 upstream of TXNIP in this pathway. SSO pharmacological blockade, NF-κB nuclear translocation assay (SN50 peptide), TXNIP gene/protein induction, apoptosis assays in INS-1 cells and primary islets Biochimica et biophysica acta Medium 26297980
2015 4-Hydroxynonenal (4-HNE) from foam cells activates PPARδ in vascular endothelial cells, leading to TXNIP upregulation; molecular manipulation of TXNIP expression confirmed its role in foam cell-induced vascular endothelial cell senescence. Co-culture transwell system, 4-HNE scavenging, siRNA/overexpression of TXNIP, PPARδ pharmacological modulation, senescence-associated β-galactosidase assay, immunofluorescence of human carotid plaques Journal of cellular and molecular medicine Medium 25754218
2016 Hyperglycemia induces activating histone marks (H3K9ac, H3K4me3, H3K4me1) and reduces repressive H3K27me3 at the TXNIP promoter in kidney mesangial cells and diabetic mouse kidneys; histone acetyltransferase p300 inhibitor C646 reverses glucose-stimulated TXNIP expression, establishing epigenetic histone acetylation as a mechanism of glucose-induced TXNIP transcription. ChIP for histone marks, histone acetyltransferase inhibitor (C646) and HDAC inhibitor (TSA), diabetic mouse kidney model, mesangial cell culture Kidney international High 26806835
2021 TXNIP directly binds STAT3 (demonstrated by Co-IP) and activates STAT3 signaling; TXNIP overexpression in tubular cells upregulates senescence markers and promotes a profibrotic response, which is suppressed by a STAT3 inhibitor, placing TXNIP upstream of STAT3 in age-related renal fibrosis. Co-immunoprecipitation of TXNIP–STAT3, Txnip-KO mice, TXNIP overexpression in tubular cells, STAT3 inhibitor epistasis Mechanisms of ageing and development Medium 33781783
2021 TXNIP contains two C-terminal PPXY motifs that mediate E3 ubiquitin ligase binding; TRAF6 ubiquitylates TXNIP via TRAF6 Cys70-dependent mechanisms, and TXNIP interacts with TRAF6 through its PPxY motif. Sodium butyrate reinforces TRAF6/TXNIP interaction and polyubiquitylation of TXNIP. Co-immunoprecipitation, ubiquitylation assays with TRAF6 C70A mutant, PPxY motif mutant analysis, siRNA knockdown Cancer medicine Medium 31578830
2021 AAV-delivered Txnip prolongs cone photoreceptor survival in retinitis pigmentosa mouse models; the C247S allele (which cannot bind thioredoxin) provides greater rescue than WT Txnip, and the rescue depends on lactate dehydrogenase b (Ldhb), implicating enhanced lactate catabolism as the mechanism by which TXNIP supports cone survival. AAV gene delivery, RP mouse models, C247S allele comparison, Ldhb genetic epistasis, visual acuity testing, mitochondrial health imaging eLife High 33847261
2022 TXNIP shuttles between different subcellular compartments—primarily nucleus under basal conditions and mitochondria under oxidative/ER stress—functioning as a gatekeeper of Trx1 (cytosol) and Trx2 (mitochondria) depending on localization; mitochondrial TXNIP promotes ROS accumulation via Trx2 oxidation, releasing ASK1 to activate apoptosis. Subcellular fractionation, immunofluorescence live-cell imaging, Chop−/− and Txnip−/− mice, mitochondrial ROS probe (68Ga-Galuminox), Co-IP Proceedings of the National Academy of Sciences of the United States of America High 35994650
2023 NEDD4L E3 ubiquitin ligase ubiquitinates TXNIP, targeting it for degradation; in NASH, decreased NEDD4L causes TXNIP protein accumulation. Accumulated TXNIP binds the N-terminus of the α-helix domain of CHOP and reduces CHOP ubiquitination, thereby increasing CHOP protein stability and promoting ER stress-mediated apoptosis in hepatocytes. Co-IP of TXNIP–CHOP domain mapping, ubiquitination assays, four NASH mouse models, adenoviral shRNA liver-specific knockdown, gain-/loss-of-function Theranostics High 37153733
2016 BioID proximity labeling identified 31 TXNIP-interacting proteins; many interactions are redox-dependent and disrupted by the C247S mutation (loss of thioredoxin binding), and hyperglycemia dynamically alters the TXNIP interactome, providing a molecular basis for its pleiotropic functions. BioID proximity labeling followed by mass spectrometry, C247S mutant comparison, hyperglycemia treatment Oxidative medicine and cellular longevity Medium 27437069
2021 TXNIP positively regulates autophagy in retinal Müller cells under high glucose by inhibiting the PI3K/AKT/mTOR signaling pathway; CRISPR/Cas9 knockout of TXNIP reduces autophagy and apoptosis under high glucose and improves visual response in diabetic retinopathy. CRISPR/Cas9 KO, overexpression, PI3K/AKT/mTOR phosphorylation western blot, electroretinogram Life sciences Medium 33412212
2022 TXNIP suppresses osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) by inhibiting BMP signaling; smooth muscle cell-specific Txnip deletion (Tagln-Cre; Txnipflox/flox) recapitulates increased atherosclerotic calcification, and BMP inhibitor K02288 abrogates the pro-osteogenic effect of TXNIP suppression in cultured VSMCs. Conditional VSMC-specific KO mice, single-cell RNA-seq, primary VSMC culture, BMP inhibitor epistasis (K02288) Circulation research High 36448450
2019 UHRF1 recruits HDAC1 to the TXNIP promoter and mediates deacetylation of histone H3K9, resulting in transcriptional silencing of TXNIP in renal cell carcinoma; UHRF1 knockdown de-represses TXNIP, and simultaneous TXNIP knockdown rescues the anti-tumor effects of UHRF1 depletion. ChIP for HDAC1 at TXNIP promoter, H3K9 acetylation ChIP, siRNA/shRNA double knockdown, xenograft tumor model Oncogene High 31043707
2022 SIRT6 transcriptionally represses TXNIP by deacetylating H3K9ac and H3K56ac at the TXNIP promoter in microglia and brain microvascular endothelial cells; this SIRT6-mediated TXNIP suppression mediates the protective effects of energy restriction/intermittent fasting on cerebral ischemia. ChIP for H3K9ac and H3K56ac at TXNIP promoter, SIRT6 overexpression, OGD/R cell model, MCAO mouse model Cell death & disease Medium 35562171
2023 USP5 deubiquitylase interacts with TXNIP (demonstrated by Co-IP) and stabilizes TXNIP protein through deubiquitylation, promoting LPS-induced apoptosis and NLRP3 inflammasome activation; USP5 knockdown reduces TXNIP levels and is reversed by TXNIP overexpression. Deubiquitylase overexpression screen, Co-immunoprecipitation, ubiquitylation assays, siRNA knockdown, epistasis rescue Hepatology communications Medium 37534934
2021 TXNIP mRNA is directly regulated by MondoA (not ChREBP) in cervical cancer cells; MondoA overexpression inhibits cell proliferation, migration, and invasion through upregulating TXNIP, placing MondoA as the upstream transcriptional inducer of TXNIP in a cell-type-dependent manner. MondoA/ChREBP overexpression, TXNIP reporter assay, siRNA knockdown, migration/invasion assays Journal of biochemistry Medium 31782782
2025 Lactic acid in the tumor microenvironment activates the MondoA–TXNIP transcriptional axis in CD8+ T cells and Tregs via SENP1-mediated de-SUMOylation of MondoA; TXNIP induction impairs TCR/CD28-signal-induced CD8+ T cell activation by restricting glucose uptake; MondoA-deficient Tregs lose immunosuppressive capacity while MondoA-deficient CD8+ T cells show enhanced cytotoxicity. MondoA conditional KO mice, SENP1 manipulation, glucose uptake assays, TCR/CD28 signaling assays, tumor models with anti-PD-1 combination, TXNIP ChIP Nature metabolism High 40846790

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 TXNIP: A key protein in the cellular stress response pathway and a potential therapeutic target. Experimental & molecular medicine 238 37394581
2018 Extracellular Matrix Remodeling Regulates Glucose Metabolism through TXNIP Destabilization. Cell 211 30197082
2020 TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation. Autophagy 179 33190588
2017 TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook. Current drug targets 174 28137209
2012 Roles of thioredoxin binding protein (TXNIP) in oxidative stress, apoptosis and cancer. Mitochondrion 147 22750447
2006 Hepatocellular carcinoma in Txnip-deficient mice. Oncogene 131 16607285
2005 Tumor suppressor VDUP1 increases p27(kip1) stability by inhibiting JAB1. Cancer research 123 15930262
2020 circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression. Molecular therapy. Nucleic acids 120 33425493
2020 Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases. International journal of molecular sciences 117 33302545
2013 Thioredoxin Interacting Protein (TXNIP) and Pathogenesis of Diabetic Retinopathy. Journal of clinical & experimental ophthalmology 109 24353900
2000 A possible interaction of thioredoxin with VDUP1 in HeLa cells detected in a yeast two-hybrid system. Biochemical and biophysical research communications 105 10814541
2007 Diverse functions of VDUP1 in cell proliferation, differentiation, and diseases. Cellular & molecular immunology 98 17976314
2006 Thioredoxin-interacting protein (txnip) is a glucocorticoid-regulated primary response gene involved in mediating glucocorticoid-induced apoptosis. Oncogene 98 16301999
2019 Thioredoxin-Interacting Protein (TXNIP) Associated NLRP3 Inflammasome Activation in Human Alzheimer's Disease Brain. Journal of Alzheimer's disease : JAD 95 30741672
2022 TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook. Oxidative medicine and cellular longevity 93 35450411
2006 Structure of the Escherichia coli ThiS-ThiF complex, a key component of the sulfur transfer system in thiamin biosynthesis. Biochemistry 92 16388576
2018 Diabetes pathogenic mechanisms and potential new therapies based upon a novel target called TXNIP. Current opinion in endocrinology, diabetes, and obesity 87 29356688
2014 Thioredoxin interacting protein (TXNIP) is a novel tumor suppressor in thyroid cancer. Molecular cancer 87 24645981
2016 Epigenetic regulation of the thioredoxin-interacting protein (TXNIP) gene by hyperglycemia in kidney. Kidney international 85 26806835
2022 Corilagin Restrains NLRP3 Inflammasome Activation and Pyroptosis through the ROS/TXNIP/NLRP3 Pathway to Prevent Inflammation. Oxidative medicine and cellular longevity 76 36299604
2020 C-terminal truncated HBx initiates hepatocarcinogenesis by downregulating TXNIP and reprogramming glucose metabolism. Oncogene 74 33323975
2021 TXNIP positively regulates the autophagy and apoptosis in the rat müller cell of diabetic retinopathy. Life sciences 68 33412212
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
2023 The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control. British journal of cancer 58 37794178
2018 Identification of thioredoxin-interacting protein (TXNIP) as a downstream target for IGF1 action. Proceedings of the National Academy of Sciences of the United States of America 56 29339473
2015 Foam cell-derived 4-hydroxynonenal induces endothelial cell senescence in a TXNIP-dependent manner. Journal of cellular and molecular medicine 53 25754218
2005 Structural analysis of Escherichia coli ThiF. Journal of molecular biology 51 15896804
2022 Blocking CHOP-dependent TXNIP shuttling to mitochondria attenuates albuminuria and mitigates kidney injury in nephrotic syndrome. Proceedings of the National Academy of Sciences of the United States of America 50 35994650
2019 UHRF1 promotes renal cell carcinoma progression through epigenetic regulation of TXNIP. Oncogene 50 31043707
2019 Oxidative stress-mediated TXNIP loss causes RPE dysfunction. Experimental & molecular medicine 50 31615975
2021 The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target. International journal of molecular sciences 49 33567593
2011 Nutrient-sensing hypothalamic TXNIP links nutrient excess to energy imbalance in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 49 21508227
2023 SIRT1 Inhibits High Glucose-Induced TXNIP/NLRP3 Inflammasome Activation and Cataract Formation. Investigative ophthalmology & visual science 48 36881408
2011 Thioredoxin regulates adipogenesis through thioredoxin-interacting protein (Txnip) protein stability. The Journal of biological chemistry 48 21705327
2001 Cloning, genetic characterization, and chromosomal mapping of the mouse VDUP1 gene. Gene 47 11376942
2022 TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis. Circulation research 43 36448450
2022 Energy restriction induced SIRT6 inhibits microglia activation and promotes angiogenesis in cerebral ischemia via transcriptional inhibition of TXNIP. Cell death & disease 40 35562171
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
2012 TXNIP in Agrp neurons regulates adiposity, energy expenditure, and central leptin sensitivity. The Journal of neuroscience : the official journal of the Society for Neuroscience 39 22815502
2009 Adenosine-containing molecules amplify glucose signaling and enhance txnip expression. Molecular endocrinology (Baltimore, Md.) 38 19246513
2023 Exercise-induced irisin improves follicular dysfunction by inhibiting IRE1α-TXNIP/ROS-NLRP3 pathway in PCOS. Journal of ovarian research 37 37525261
2021 Thioredoxin-interacting protein (TXNIP) as a target for Alzheimer's disease: flavonoids and phenols. Inflammopharmacology 37 34350508
2021 AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa. eLife 36 33847261
2021 Ligustrazine alleviates cyclophosphamide-induced hepatotoxicity via the inhibition of Txnip/Trx/NF-κB pathway. Life sciences 34 33716060
2024 Coptisine alleviates colitis through modulating gut microbiota and inhibiting TXNIP/NLRP3 inflammasome. Journal of ethnopharmacology 33 39117021
2020 Thioredoxin interacting protein (TXNIP) acts as a tumor suppressor in human prostate cancer. Cell biology international 31 32639616
2021 Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation. Lipids in health and disease 30 33612104
2017 Estradiol Regulates Txnip and Prevents Intermittent Hypoxia-Induced Vascular Injury. Scientific reports 30 28871193
2023 PIAS3 promotes ferroptosis by regulating TXNIP via TGF-β signaling pathway in hepatocellular carcinoma. Pharmacological research 29 37689128
2022 Calycosin modulates NLRP3 and TXNIP-mediated pyroptotic signaling and attenuates diabetic nephropathy progression in diabetic rats; An insight. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 36271546
2021 HOXA9-induced chemerin signals through CMKLR1/AMPK/TXNIP/NLRP3 pathway to induce pyroptosis of trophoblasts and aggravate preeclampsia. Experimental cell research 26 34461109
2019 Sodium butyrate-activated TRAF6-TXNIP pathway affects A549 cells proliferation and migration. Cancer medicine 26 31578830
2020 Estrogen protects neuroblastoma cell from amyloid-β 42 (Aβ42)-induced apoptosis via TXNIP/TRX axis and AMPK signaling. Neurochemistry international 24 31931042
2020 Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling. Cells 24 32164364
2024 Circ6834 suppresses non-small cell lung cancer progression by destabilizing ANHAK and regulating miR-873-5p/TXNIP axis. Molecular cancer 23 38890620
2020 TXNIP induced by MondoA, rather than ChREBP, suppresses cervical cancer cell proliferation, migration and invasion. Journal of biochemistry 23 31782782
2023 Memantine mitigates ROS/TXNIP/NLRP3 signaling and protects against mouse diabetic retinopathy: Histopathologic, ultrastructural and bioinformatic studies. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 22 37116352
2022 TXNIP Links Anticipatory Unfolded Protein Response to Estrogen Reprogramming Glucose Metabolism in Breast Cancer Cells. Endocrinology 22 34614512
2022 Ferulic acid relieved ulcerative colitis by inhibiting the TXNIP/NLRP3 pathway in rats. Cell biology international 22 36251276
2020 Targeting endothelial thioredoxin-interacting protein (TXNIP) protects from metabolic disorder-related impairment of vascular function and post-ischemic revascularisation. Angiogenesis 22 31900750
2024 TXNIP-mediated crosstalk between oxidative stress and glucose metabolism. PloS one 21 38329960
2021 Long Non-coding RNA GAS5 Worsens Coronary Atherosclerosis Through MicroRNA-194-3p/TXNIP Axis. Molecular neurobiology 21 33638792
2021 Role and mechanism of TXNIP in ageing-related renal fibrosis. Mechanisms of ageing and development 21 33781783
2023 ChREBP-β/TXNIP aggravates frucose-induced renal injury through triggering ferroptosis of renal tubular epithelial cells. Free radical biology & medicine 20 36828294
2021 Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways. Evidence-based complementary and alternative medicine : eCAM 20 34804174
2015 A novel TXNIP-based mechanism for Cx43-mediated regulation of oxidative drug injury. Journal of cellular and molecular medicine 20 26154105
2015 CD36 initiated signaling mediates ceramide-induced TXNIP expression in pancreatic beta-cells. Biochimica et biophysica acta 20 26297980
2021 Dual regulation of TxNIP by ChREBP and FoxO1 in liver. iScience 19 33748706
2019 O-GlcNacylation Links TxNIP to Inflammasome Activation in Pancreatic β Cells. Frontiers in endocrinology 19 31164864
2023 A novel NEDD4L-TXNIP-CHOP axis in the pathogenesis of nonalcoholic steatohepatitis. Theranostics 18 37153733
2022 Celastrol targets the ChREBP-TXNIP axis to ameliorates type 2 diabetes mellitus. Phytomedicine : international journal of phytotherapy and phytopharmacology 18 36603341
2024 The ROS/TXNIP/NLRP3 pathway mediates LPS-induced microglial inflammatory response. Cytokine 17 38896955
2024 piR112710 attenuates diabetic cardiomyopathy through inhibiting Txnip/NLRP3-mediated pyroptosis in db/db mice. Cellular signalling 17 39102928
2022 Fluoxetine increases astrocytic glucose uptake and glycolysis in corticosterone-induced depression through restricting GR-TXNIP-GLUT1 Pathway. Frontiers in pharmacology 17 36105196
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 16 36760500
2022 Overview on Thioredoxin-Interacting Protein (TXNIP): A Potential Target for Diabetes Intervention. Current drug targets 16 35240955
2022 Verapamil inhibits TXNIP-NLRP3 inflammasome activation and preserves functional recovery after intracerebral hemorrhage in mice. Neurochemistry international 16 36244583
2021 Colorectal Cancer Cell Differentiation Is Dependent on the Repression of Aerobic Glycolysis by NDRG2-TXNIP Axis. Digestive diseases and sciences 16 34373985
2021 ChREBP deficiency alleviates apoptosis by inhibiting TXNIP/oxidative stress in diabetic nephropathy. Journal of diabetes and its complications 16 34600826
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
2023 BCR-ABL triggers a glucose-dependent survival program during leukemogenesis through the suppression of TXNIP. Cell death & disease 15 37095099
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.) 15 37749991
2024 PTBP1 knockdown impairs autophagy flux and inhibits gastric cancer progression through TXNIP-mediated oxidative stress. Cellular & molecular biology letters 14 39153986
2022 N-Lobe of TXNIP Is Critical in the Allosteric Regulation of NLRP3 via TXNIP Binding. Frontiers in aging neuroscience 14 35721021
2022 Ceramide induces pyroptosis through TXNIP/NLRP3/GSDMD pathway in HUVECs. BMC molecular and cell biology 14 36517743
2021 Geniposide improves insulin resistance through AMPK-mediated Txnip protein degradation in 3T3-L1 adipocytes. Acta biochimica et biophysica Sinica 14 33349852
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
2018 TXNIP knockdown alleviates hepatocyte ischemia reperfusion injury through preventing p38/JNK pathway activation. Biochemical and biophysical research communications 14 29852169
2025 Beyond Redox Regulation: Novel Roles of TXNIP in the Pathogenesis and Therapeutic Targeting of Kidney Disease. The American journal of pathology 13 39814099
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
2016 Identification of Redox and Glucose-Dependent Txnip Protein Interactions. Oxidative medicine and cellular longevity 13 27437069
2025 Targeting MondoA-TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment. Nature metabolism 12 40846790
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
2022 Maslinic Acid Suppresses High Glucose-induced Inflammation by Epigenetically Inhibiting TXNIP Expression. Current medical science 12 36350490
2021 Antidiabetic effects of quercetin and liraglutide combination through modulation of TXNIP/IRS-1/PI3K pathway. Cell biochemistry and function 11 34855213