Affinage

TXNRD2

Thioredoxin reductase 2, mitochondrial · UniProt Q9NNW7

Length
524 aa
Mass
56.5 kDa
Annotated
2026-04-28
100 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TXNRD2 encodes a selenocysteine-containing mitochondrial thioredoxin reductase that is essential for mitochondrial redox homeostasis, controlling reactive oxygen species levels, peroxynitrite detoxification, and downstream signaling in multiple tissues. In the heart, loss of TXNRD2 causes dilated cardiomyopathy with mitochondrial degeneration, dysregulated autophagy, and HIF-1α stabilization, while in endothelium it shifts the nitric oxide/peroxynitrite balance toward peroxynitrite accumulation, oxidizes peroxiredoxin-3, and drives vascular pathology (PMID:21247928, PMID:26199228, PMID:33579817). TXNRD2 expression is regulated by the Nrf2–KLF9 axis and the Wnt/β-catenin pathway, and its suppression elevates mitochondrial ROS that can activate PI3K/Akt signaling, promote cellular senescence, or trigger the NLRP3 inflammasome (PMID:22683372, PMID:36569930, PMID:32671444). Homozygous loss-of-function mutations in TXNRD2 cause familial glucocorticoid deficiency in humans, and dominant-negative mutations in its FAD-binding domain cause dilated cardiomyopathy (PMID:24601690, PMID:21247928).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2003 Medium

    The first evidence that TrxR2 loss of function has signaling consequences was established: dominant-negative TrxR2 increased mitochondrial H₂O₂, enhanced tyrosine phosphorylation including ERK, and accelerated cell proliferation, revealing that TrxR2 normally restrains mitochondrial ROS-driven growth signaling.

    Evidence Tetracycline-regulated dominant-negative TrxR2 in HeLa cells with H₂O₂ measurement, phospho-tyrosine blots, and cell cycle analysis

    PMID:12705894

    Open questions at the time
    • Single dominant-negative approach without genetic knockout confirmation
    • Mechanism connecting mitochondrial H₂O₂ to ERK activation not delineated
    • No in vivo validation
  2. 2004 High

    TrxR2 was confirmed to localize to mitochondria via EGFP fusion and shown to be enzymatically active, but overexpression did not protect against apoptosis, delimiting its gain-of-function capacity.

    Evidence EGFP-TrxR2 fusion protein in Neuro2A, COS-7, and HeLa cells; TrxR activity assay; apoptosis assays with multiple inducers

    PMID:15082714

    Open questions at the time
    • Overexpression may not recapitulate physiological redox buffering capacity
    • Loss-of-function not tested in this study
  3. 2011 High

    TXNRD2 was directly linked to human dilated cardiomyopathy: two independent missense mutations in the FAD-binding domain abolished TrxR2 activity and exerted dominant-negative effects on wild-type enzyme, establishing the first Mendelian disease association.

    Evidence Sequencing of DCM patients; functional rescue in Txnrd2−/− mouse fibroblasts; co-expression demonstrating dominant-negative mechanism

    PMID:21247928

    Open questions at the time
    • No crystal structure of mutant enzymes to explain dominant-negative mechanism
    • Penetrance and modifier effects in human families not fully characterized
  4. 2012 Medium

    TXNRD2 transcription was placed downstream of Wnt/β-catenin signaling in intestinal epithelium, and the C. elegans ortholog trxr-2 was shown to function in muscle tissues affecting longevity under stress, broadening the tissue and evolutionary scope of mitochondrial TrxR function.

    Evidence Wnt-modulated cancer cell lines and β-catenin conditional knockout in murine colonic crypts; C. elegans trxr-2 deletion mutant with longevity and stress phenotypes

    PMID:22683372 PMID:22836943

    Open questions at the time
    • No direct promoter-binding data for β-catenin at the TXNRD2 locus
    • C. elegans phenotype may not fully translate to mammalian physiology
  5. 2014 High

    A second human Mendelian disease — familial glucocorticoid deficiency — was attributed to homozygous TXNRD2 loss-of-function (p.Y447X), with knockdown in adrenocortical cells confirming impaired redox homeostasis, establishing TXNRD2 as essential for adrenal steroidogenesis.

    Evidence Whole-exome sequencing with family segregation; TXNRD2 knockdown in H295R adrenocortical cells with redox assays

    PMID:24601690

    Open questions at the time
    • Precise steroidogenic step regulated by TXNRD2 redox control not identified
    • Whether adrenal phenotype involves peroxynitrite (as later shown in endothelium) not tested
  6. 2015 High

    Heart-specific conditional Txnrd2 knockout in adult mice recapitulated human DCM with mitochondrial degeneration, dysregulated autophagy, elevated ROS, and HIF-1α stabilization, providing the mechanistic in vivo framework for TXNRD2 cardiomyopathy.

    Evidence Tamoxifen-inducible αMHC-MerCreMer Txnrd2 knockout mouse; echocardiography; electron microscopy; isolated mitochondria respirometry; metabolic profiling

    PMID:26199228

    Open questions at the time
    • Whether HIF-1α stabilization is cause or consequence of mitochondrial dysfunction not resolved
    • Rescue experiments (e.g., antioxidant supplementation) not performed
  7. 2016 Medium

    TrxR2 knockdown in chondrogenic cells increased mitochondrial ROS, enhanced differentiation via Akt activation, and induced apoptosis — all rescued by NAC — positioning TrxR2 as a mitochondrial ROS rheostat that regulates cell fate decisions beyond cardiomyocytes.

    Evidence shRNA knockdown in ATDC5 cells; mitochondrial ROS measurement; NAC rescue; differentiation markers and Akt Western blot

    PMID:27107686

    Open questions at the time
    • Single cell line (ATDC5)
    • Whether Akt activation is direct or via intermediate kinases unknown
  8. 2021 High

    Endothelial-specific Txnrd2 deletion revealed that TrxR2 is the master controller of the NO/peroxynitrite balance in vasculature: loss shifted Prx3 to its oxidized form, elevated peroxynitrite and protein tyrosine nitration, and caused vascular stiffness and renal pathology — all rescued by a peroxynitrite decomposition catalyst.

    Evidence Endothelial Txnrd2 knockout mouse; fluorescein-boronate and MitoPY1 probes; peroxynitrite decomposition catalyst rescue; Prx3 redox Western blot; renal histology

    PMID:33579817

    Open questions at the time
    • Whether peroxynitrite-driven damage feeds back to further impair TrxR2 not tested
    • Contribution of TrxR2 versus TrxR1 in non-endothelial vascular cells not addressed
  9. 2022 Medium

    TXNRD2 was placed within the Nrf2–KLF9 transcriptional axis as a downstream effector that suppresses NLRP3 inflammasome activation by controlling mitochondrial ROS in macrophages, integrating its antioxidant function with innate immune regulation.

    Evidence LXA4-treated macrophages; TXNRD2 siRNA epistasis; NLRP3 inflammasome assembly assays (ASC speck, co-IP); Nrf2 and KLF9 Western blot; gouty arthritis rat model

    PMID:36569930

    Open questions at the time
    • Direct Nrf2 or KLF9 binding at the TXNRD2 promoter not demonstrated by ChIP
    • Single inflammatory model (gout); generalizability to other inflammasome triggers unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for dominant-negative inhibition by FAD-domain mutants, whether the peroxynitrite-scavenging function identified in endothelium also underlies the adrenal and cardiac phenotypes, and the identity of direct TXNRD2 substrates beyond thioredoxin-2/Prx3 that mediate its tissue-specific effects.
  • No crystal structure of human TXNRD2 mutants
  • Peroxynitrite mechanism not tested in adrenal or cardiac models
  • Full substrate repertoire in mitochondria not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0016209 antioxidant activity 3
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-8953897 Cellular responses to stimuli 5 R-HSA-1643685 Disease 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-168256 Immune System 1
Partners
KLF9NRF2PRDX3TXN2

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 TrxR2 (TXNRD2) overexpression localizes to mitochondria (confirmed by EGFP-TrxR2 fusion protein) and is enzymatically active, but excess TrxR2 does not protect mammalian cells against apoptotic inducers, suggesting TrxR2 gain-of-function does not modify redox regulation of mitochondria-dependent apoptosis under the tested conditions. Stable transfection of EGFP-TrxR2 fusion protein in Neuro2A, COS-7, and HeLa cells; mitochondrial localization confirmed; TrxR activity assays; apoptosis assays with multiple inducers The Journal of biological chemistry High 15082714
2011 Loss-of-function TXNRD2 mutations (Ala59Thr and Gly375Arg) in the FAD-binding domain of human TXNRD2 cause dilated cardiomyopathy (DCM); both mutations abolish TrxR2 function and exert dominant-negative effects on wild-type Txnrd2 in mouse fibroblasts under oxidative stress. Sequencing of TXNRD2 in DCM patients; functional rescue assay in Txnrd2−/− mouse fibroblasts; dominant-negative mechanism established by co-expression with wild-type European heart journal High 21247928
2014 A homozygous stop-gain mutation (p.Y447X) in TXNRD2 causes familial glucocorticoid deficiency (FGD) in humans; TXNRD2 deficiency leads to impaired redox homeostasis in a human adrenocortical cell line (H295R TXNRD2-knockdown), establishing TXNRD2 as essential for adrenal steroidogenesis. Whole-exome sequencing; Sanger segregation analysis; RT-PCR and Western blot confirming absence of protein; TXNRD2-knockdown H295R cell line with redox assays The Journal of clinical endocrinology and metabolism High 24601690
2015 Inducible, heart-specific Txnrd2 knockout in adult mice causes dilated cardiomyopathy with mitochondrial degeneration, dysregulated autophagy (elevated LAMP1, LC3-I, p62), reduced mitochondrial oxygen consumption, increased ROS production, and chronic HIF-1α stabilization, establishing Txnrd2 as essential for cardiac mitochondrial homeostasis during aging. Tamoxifen-inducible αMHC-MerCreMer Txnrd2 conditional knockout mouse; echocardiography; ultrastructural analysis; isolated mitochondria functional assays; metabolic/transcriptional profiling Journal of the American Heart Association High 26199228
2021 Endothelial-specific deletion of Trxrd2 in mice increases steady-state peroxynitrite levels in vascular endothelial cells and vessels (measured with fluorescein-boronate probe and MitoPY1), shifts Prx3 toward the oxidized form, elevates protein tyrosine nitration, and results in vascular stiffness, wall hypertrophy, and renal pathology, establishing TrxR2 as the key controller of the nitric oxide/peroxynitrite balance in endothelium. Endothelial-specific Trxrd2 knockout mouse; fluorescein-boronate redox probe; MitoPY1 mitochondrial peroxynitrite probe; peroxynitrite decomposition catalyst rescue; Western blot for Prx3 redox state; renal histology Proceedings of the National Academy of Sciences of the United States of America High 33579817
2003 Expression of a dominant-negative form of TrxR2 in HeLa cells increases hydrogen peroxide production upon EGF stimulation, elevates protein tyrosine phosphorylation (including ERK), accelerates G1-to-S phase progression, and increases cell proliferation, indicating that TrxR2 participates in regulating the mitochondrial H2O2-eliminating system and thereby modulates cell growth signaling. Stable HeLa cells with tetracycline-off dominant-negative TrxR2; H2O2 measurement; phospho-tyrosine Western blot; cell cycle analysis; proliferation assay Biochemical and biophysical research communications Medium 12705894
2012 TXNRD2 (TrxR2) expression in intestinal epithelial cells is regulated by the Wnt/β-catenin pathway; TrxR2 levels are higher in proliferative crypt compartments (where Wnt is active) and decrease upon β-catenin deletion in colonic crypt cells, identifying TrxR2 as a novel Wnt target gene. Cancer cell lines with activated/inhibited Wnt pathway; mouse intestinal crypt/villus fractionation; inducible β-catenin knockout in colonic crypt cells; qRT-PCR and protein expression Biochimica et biophysica acta Medium 22683372
2017 Mitocurcumin binds to the active site of TrxR2 (docking studies confirmed, TrxR activity decreased in cell-free and cellular systems) and modulates TrxR2 to an NADPH oxidase-like activity, resulting in increased mitochondrial ROS, and cell death is accentuated by TrxR2 overexpression, establishing TrxR2 active site as the mechanistic target of mitocurcumin. Molecular docking of mitocurcumin to TrxR2 active site; cell-free TrxR activity assay; cellular TrxR activity assay; TrxR2 overexpression in lung cancer cells; ROS measurement; apoptosis assays Free radical biology & medicine Medium 29080841
2016 TrxR2 deficiency in chondrogenic ATDC5 cells (via shRNA) increases mitochondrial ROS without altering mitochondrial membrane potential or ATP, enhances chondrogenic differentiation (GAG accumulation, collagen II/aggrecan expression, Akt activation), and induces apoptosis; NAC (ROS scavenger) rescues these phenotypes, establishing TrxR2-controlled mitochondrial ROS as a regulator of chondrogenic differentiation and chondrocyte survival. shRNA-mediated TrxR2 knockdown in ATDC5 cells; mitochondrial ROS measurement; NAC rescue; differentiation markers; apoptosis assays; Akt signaling Western blot Experimental cell research Medium 27107686
2017 miR-195-5p directly targets the 3′UTR of TrxR2 (validated by dual-luciferase reporter assay); TrxR2 knockdown phenocopies miR-195-5p overexpression (suppressed proliferation, migration, invasion; increased apoptosis in LUAD cells), and TrxR2 overexpression rescues miR-195-5p effects, establishing TrxR2 as a functional downstream target of miR-195-5p in lung adenocarcinoma. Dual-luciferase reporter assay for 3′UTR targeting; lentiviral TrxR2 overexpression/shRNA knockdown; CCK-8, EdU, transwell, flow cytometry assays; in vivo xenograft Acta biochimica et biophysica Sinica Medium 33332541
2020 Wogonin reduces TXNRD2 expression by altering histone acetylation at its regulatory region, leading to ROS accumulation and cellular senescence in TNBC cells; NAC rescues wogonin-induced senescence, mechanistically linking TXNRD2 epigenetic suppression to ROS-dependent senescence. Wogonin treatment of MDA-MB-231 cells; β-galactosidase activity; histone acetylation ChIP at TXNRD2 promoter; ROS measurement; NAC rescue; Western blot for TXNRD2 Archives of toxicology Medium 32671444
2022 The Nrf2 pathway regulates TXNRD2 expression; LXA4 suppresses Nrf2 activation, which increases KLF9 expression and promotes TXNRD2 expression; TXNRD2 knockdown reverses LXA4-mediated ROS suppression and NLRP3 inflammasome inhibition in macrophages, establishing TXNRD2 as a downstream effector in the Nrf2-KLF9-TXNRD2 antioxidant axis controlling NLRP3 inflammasome activity. LXA4 treatment of macrophages; TXNRD2 siRNA knockdown; ROS measurement; NLRP3 inflammasome assembly assays (ASC oligomerization, speck formation, co-IP); Western blot for Nrf2, KLF9, TXNRD2; gouty arthritis rat model Frontiers in immunology Medium 36569930
2012 In C. elegans, trxr-2 (mitochondrial TrxR ortholog of TXNRD2) is expressed mainly in pharyngeal and body wall muscles; its deletion causes defects in longevity and delayed development under stress conditions, while the cytosolic trxr-1 deletion causes lysosomal acidification defects, demonstrating distinct physiological roles for the two TrxR isoforms. GFP reporter expression analysis; deletion mutant characterization; longevity assay; development timing under stress; lysosomal acidification assay in C. elegans Molecules and cells Medium 22836943
2018 The mitochondria-targeted compound BTPA selectively inhibits TrxR2 in mitochondria, causing ROS accumulation, PI3K/Akt signaling attenuation, cytochrome c release, and caspase-9 activation; NAC fully reverses these effects, placing TrxR2 upstream of the mitochondrial ROS/PI3K/Akt/intrinsic apoptosis axis. Confocal colocalization (BTPA mitochondrial distribution); TrxR2 inhibition assay; ROS measurement (DCFH-DA); cytochrome c release; caspase-9 activation; NAC rescue; Akt signaling Western blot in BGC-823 cells International journal of pharmaceutics Low 30500459
2016 GSK-3β inhibition activates the Nrf2/TrxR2 signaling pathway in diabetic rat kidneys subjected to ischemia/reperfusion injury, reducing oxidative stress and apoptosis; auranofin (TrxR inhibitor) reverses protection, placing TrxR2 downstream of Nrf2 as a key renoprotective antioxidant effector. Diabetic rat model; TDZD-8 (GSK-3β inhibitor) treatment; auranofin co-treatment; BUN/Scr measurement; SOD activity; MDA; Nrf2 and TrxR2 expression by Western blot; caspase-3 expression Kidney & blood pressure research Low 27924803

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell 586 14980220
2000 Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science (New York, N.Y.) 574 10947977
1993 Determinants for selective RAR and TR recognition of direct repeat HREs. Genes & development 355 8392478
2006 p53 and Nur77/TR3 - transcription factors that directly target mitochondria for cell death induction. Oncogene 212 16892086
2016 Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nature genetics 204 26752265
2005 TRP channels: a TR(I)P through a world of multifunctional cation channels. Pflugers Archiv : European journal of physiology 183 16012814
2003 Mitogenic effect of orphan receptor TR3 and its regulation by MEKK1 in lung cancer cells. Molecular and cellular biology 172 14612408
2004 Retinoid X receptor regulates Nur77/TR3-dependent apoptosis [corrected] by modulating its nuclear export and mitochondrial targeting. Molecular and cellular biology 161 15509776
2006 Orphan nuclear receptor TR3/Nur77 regulates VEGF-A-induced angiogenesis through its transcriptional activity. The Journal of experimental medicine 137 16520388
2002 Protective function of transcription factor TR3 orphan receptor in atherogenesis: decreased lesion formation in carotid artery ligation model in TR3 transgenic mice. Circulation 134 12234960
2002 Tr-kit-induced resumption of the cell cycle in mouse eggs requires activation of a Src-like kinase. The EMBO journal 110 12374739
2011 The nuclear receptor TR3 regulates mTORC1 signaling in lung cancer cells expressing wild-type p53. Oncogene 103 22081070
2008 On the origin of bladder sensing: Tr(i)ps in urology. Neurourology and urodynamics 97 17849480
2003 TR3/Nur77 in colon cancer cell apoptosis. Cancer research 97 14500374
1994 NOT, a human immediate-early response gene closely related to the steroid/thyroid hormone receptor NAK1/TR3. Molecular endocrinology (Baltimore, Md.) 94 7877627
2004 Mitochondrial thioredoxin system: effects of TrxR2 overexpression on redox balance, cell growth, and apoptosis. The Journal of biological chemistry 90 15082714
2014 Thioredoxin Reductase 2 (TXNRD2) mutation associated with familial glucocorticoid deficiency (FGD). The Journal of clinical endocrinology and metabolism 88 24601690
2002 TR surfaces and conformations required to bind nuclear receptor corepressor. Molecular endocrinology (Baltimore, Md.) 88 11818500
2011 Targeting NR4A1 (TR3) in cancer cells and tumors. Expert opinion on therapeutic targets 87 21204731
2017 ARResT/Interrogate: an interactive immunoprofiler for IG/TR NGS data. Bioinformatics (Oxford, England) 86 28172348
2011 Mutations in the mitochondrial thioredoxin reductase gene TXNRD2 cause dilated cardiomyopathy. European heart journal 80 21247928
2013 The vascular permeabilizing factors histamine and serotonin induce angiogenesis through TR3/Nur77 and subsequently truncate it through thrombospondin-1. Blood 76 23315169
2019 Quality control and quantification in IG/TR next-generation sequencing marker identification: protocols and bioinformatic functionalities by EuroClonality-NGS. Leukemia 75 31227779
2019 A TR(i)P to Cell Migration: New Roles of TRP Channels in Mechanotransduction and Cancer. Frontiers in physiology 73 31275168
2009 Development and applications of a broad-coverage, TR-FRET-based kinase binding assay platform. Journal of biomolecular screening 70 19564447
2011 The orphan receptor TR3 suppresses intestinal tumorigenesis in mice by downregulating Wnt signalling. Gut 67 21873734
2009 Activity of oxazolidinone TR-700 against linezolid-susceptible and -resistant staphylococci and enterococci. The Journal of antimicrobial chemotherapy 65 19164418
1998 Antisense TR3 orphan receptor can increase prostate cancer cell viability with etoposide treatment. Endocrinology 65 9564841
2006 p53 mediates the negative regulation of MDM2 by orphan receptor TR3. The EMBO journal 64 17139261
2010 Spontaneous quaternary and tertiary T-R transitions of human hemoglobin in molecular dynamics simulation. PLoS computational biology 60 20463873
2004 Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor-kappaB. Nucleic acids research 60 15466594
2017 Mitochondrial targeted curcumin exhibits anticancer effects through disruption of mitochondrial redox and modulation of TrxR2 activity. Free radical biology & medicine 58 29080841
2011 Activation of nuclear TR3 (NR4A1) by a diindolylmethane analog induces apoptosis and proapoptotic genes in pancreatic cancer cells and tumors. Carcinogenesis 57 21362629
2006 TR3 nuclear orphan receptor prevents cyclic stretch-induced proliferation of venous smooth muscle cells. The American journal of pathology 57 16723716
2004 RXRalpha acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells. Journal of cell science 55 15494375
2014 New insights into pharmacological tools to TR(i)P cancer up. British journal of pharmacology 53 24345078
2008 IG, TR and IgSF, MHC and MhcSF: what do we learn from the IMGT Colliers de Perles? Briefings in functional genomics & proteomics 53 18208865
2020 Wogonin induces cellular senescence in breast cancer via suppressing TXNRD2 expression. Archives of toxicology 51 32671444
2007 Involvement of TR3/Nur77 translocation to the endoplasmic reticulum in ER stress-induced apoptosis. Experimental cell research 50 17543302
2021 The mitochondrial thioredoxin reductase system (TrxR2) in vascular endothelium controls peroxynitrite levels and tissue integrity. Proceedings of the National Academy of Sciences of the United States of America 49 33579817
2012 The selenoproteins GPx2, TrxR2 and TrxR3 are regulated by Wnt signalling in the intestinal epithelium. Biochimica et biophysica acta 49 22683372
2009 A TR(I)P to pruritus research: role of TRPV3 in inflammation and itch. The Journal of investigative dermatology 49 19209153
2015 NF-κB inhibitor reverses temozolomide resistance in human glioma TR/U251 cells. Oncology letters 48 26137111
2015 Heart-Specific Knockout of the Mitochondrial Thioredoxin Reductase (Txnrd2) Induces Metabolic and Contractile Dysfunction in the Aging Myocardium. Journal of the American Heart Association 47 26199228
2011 Therapeutic targeting of TRP channels--the TR(i)P to pain relief. Current topics in medicinal chemistry 47 21671881
2014 Non-genomic effects of the NR4A1/Nur77/TR3/NGFIB orphan nuclear receptor. Steroids 46 25555471
2013 SNP in TXNRD2 associated with radiation-induced fibrosis: a study of genetic variation in reactive oxygen species metabolism and signaling. International journal of radiation oncology, biology, physics 46 23597419
2002 Structure-based design and synthesis of a thyroid hormone receptor (TR) antagonist. Endocrinology 45 11796506
2012 The orphan receptor TR3 participates in angiotensin II-induced cardiac hypertrophy by controlling mTOR signalling. EMBO molecular medicine 43 23197407
2004 ERK2 prohibits apoptosis-induced subcellular translocation of orphan nuclear receptor NGFI-B/TR3. The Journal of biological chemistry 43 15448159
2002 TR(beta)1 protein is preferentially expressed in the pericentral zone of rat liver and exhibits marked diurnal variation. Endocrinology 43 11861522
2002 Induction of apoptosis by TPA and VP-16 is through translocation of TR3. World journal of gastroenterology 43 12046067
2017 Thyroid hormone regulates hematopoiesis via the TR-KLF9 axis. Blood 42 28972010
2016 GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats. Kidney & blood pressure research 41 27924803
2003 TR3 orphan nuclear receptor mediates apoptosis through up-regulating E2F1 in human prostate cancer LNCaP cells. The Journal of biological chemistry 41 12947120
1985 Localization of agropine-synthesizing functions in the TR region of the root-inducing plasmid of Agrobacterium rhizogenes 1855. Plasmid 41 3991808
2011 Prolyl isomerase Pin1 stabilizes and activates orphan nuclear receptor TR3 to promote mitogenesis. Oncogene 39 22002310
2008 Akt phosphorylates the TR3 orphan receptor and blocks its targeting to the mitochondria. Carcinogenesis 39 18713840
2014 Orphan nuclear receptor TR3/Nur77 improves wound healing by upregulating the expression of integrin β4. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 25326539
1984 Genetic identification of functions of TR-DNA transcripts in octopine crown galls. The EMBO journal 38 16453491
2008 A feedback regulatory loop between methyltransferase PRMT1 and orphan receptor TR3. Nucleic acids research 37 19095693
2022 Characterization of TR-107, a novel chemical activator of the human mitochondrial protease ClpP. Pharmacology research & perspectives 36 35929764
2008 Induction of apoptosis in PA-1 ovarian cancer cells by vitamin K2 is associated with an increase in the level of TR3/Nur77 and its accumulation in mitochondria and nuclei. Journal of cancer research and clinical oncology 35 18202854
2020 Evolution of the T-Cell Receptor (TR) Loci in the Adaptive Immune Response: The Tale of the TRG Locus in Mammals. Genes 33 32517024
2014 Dual roles of orphan nuclear receptor TR3/Nur77/NGFI-B in mediating cell survival and apoptosis. International review of cell and molecular biology 33 25376494
2007 Orphan receptor TR3 attenuates the p300-induced acetylation of retinoid X receptor-alpha. Molecular endocrinology (Baltimore, Md.) 33 17761950
2003 Involvements of mitochondrial thioredoxin reductase (TrxR2) in cell proliferation. Biochemical and biophysical research communications 32 12705894
2022 Inhibition of Glutamine Uptake Resensitizes Paclitaxel Resistance in SKOV3-TR Ovarian Cancer Cell via mTORC1/S6K Signaling Pathway. International journal of molecular sciences 30 35955892
2006 Regulation of the orphan receptor TR3 nuclear functions by c-Jun N terminal kinase phosphorylation. Endocrinology 30 17023523
2012 Two thioredoxin reductases, trxr-1 and trxr-2, have differential physiological roles in Caenorhabditis elegans. Molecules and cells 29 22836943
2009 TR-700 in vitro activity against and resistance mutation frequencies among Gram-positive pathogens. The Journal of antimicrobial chemotherapy 29 19218276
2022 DSM-5-TR: Rationale, Process, and Overview of Changes. Psychiatric services (Washington, D.C.) 28 36510761
2020 Prevalence and Genetic Diversity of Staphylococcal Enterotoxin (-Like) Genes sey, selw, selx, selz, sel26 and sel27 in Community-Acquired Methicillin-Resistant Staphylococcus aureus. Toxins 28 32456224
2018 Transient receptor potential (TRP) channels: a metabolic TR(i)P to obesity prevention and therapy. Obesity reviews : an official journal of the International Association for the Study of Obesity 28 29797770
2012 Orphan receptor TR3 is essential for the maintenance of stem-like properties in gastric cancer cells. Cancer letters 28 23043761
2011 Orphan receptor TR3 participates in cisplatin-induced apoptosis via Chk2 phosphorylation to repress intestinal tumorigenesis. Carcinogenesis 28 22159226
2008 Brain TRPV1: a depressing TR(i)P down memory lane? Trends in pharmacological sciences 28 18947889
1991 Tissue-specific and stress-enhancing expression of the TR promoter for mannopine synthase in transgenic medicinal plants. Planta 28 24193927
2024 Analysis of measurable residual disease by IG/TR gene rearrangements: quality assurance and updated EuroMRD guidelines. Leukemia 27 38744919
2020 Azole-Resistant Aspergillus fumigatus Among Danish Cystic Fibrosis Patients: Increasing Prevalence and Dominance of TR34/L98H. Frontiers in microbiology 27 32903400
2022 Lipoxin A4 attenuates MSU-crystal-induced NLRP3 inflammasome activation through suppressing Nrf2 thereby increasing TXNRD2. Frontiers in immunology 26 36569930
2014 Novel treatment option for MUC16-positive malignancies with the targeted TRAIL-based fusion protein Meso-TR3. BMC cancer 26 24447304
2007 Nuclear orphan receptor TR3/Nur77 mediates melanoma cell apoptosis. Cancer biology & therapy 25 17297306
2017 Inhibition of TrxR2 suppressed NSCLC cell proliferation, metabolism and induced cell apoptosis through decreasing antioxidant activity. Life sciences 24 28414076
2023 Development of a high-throughput TR-FRET screening assay for LAG-3/FGL1 interaction. SLAS discovery : advancing life sciences R & D 23 37121273
2018 Orphan nuclear receptor TR3/Nur77 differentially regulates the expression of integrins in angiogenesis. Microvascular research 23 30391133
2014 RXR agonist modulates TR: corepressor dissociation upon 9-cis retinoic acid treatment. Molecular endocrinology (Baltimore, Md.) 23 25541638
2013 The orphan nuclear receptor TR3/Nur77 regulates ER stress and induces apoptosis via interaction with TRAPγ. The international journal of biochemistry & cell biology 23 23660295
1989 Extracorporeal immunoadsorption with IM-PH or IM-TR column. Biomaterials, artificial cells, and artificial organs 23 2673426
2018 Smart mitochondrial-targeted cancer therapy: Subcellular distribution, selective TrxR2 inhibition accompany with declined antioxidant capacity. International journal of pharmaceutics 22 30500459
1994 Expression of the NK-TR gene is required for NK-like activity in human T cells. Journal of immunology (Baltimore, Md. : 1950) 22 8144875
2016 TrxR2 deficiencies promote chondrogenic differentiation and induce apoptosis of chondrocytes through mitochondrial reactive oxygen species. Experimental cell research 21 27107686
2015 Single nucleotide polymorphisms in the Trx2/TXNIP and TrxR2 genes of the mitochondrial thioredoxin antioxidant system and the risk of diabetic retinopathy in patients with Type 2 diabetes mellitus. Journal of diabetes and its complications 21 26763822
2017 Using TR-FRET to Investigate Protein-Protein Interactions: A Case Study of PXR-Coregulator Interaction. Advances in protein chemistry and structural biology 20 29412999
2014 TR-FRET assays of Huntingtin protein fragments reveal temperature and polyQ length-dependent conformational changes. Scientific reports 20 24998512
2011 Norcantharidin induces melanoma cell apoptosis through activation of TR3 dependent pathway. Cancer biology & therapy 20 22123174
2000 Neuron-specific localisation of the TR3 death receptor in Alzheimer's disease. Brain research 20 10700560
2021 miR-195-5p exerts tumor-suppressive functions in human lung cancer cells through targeting TrxR2. Acta biochimica et biophysica Sinica 18 33332541
2017 Unphosphorylated EIIANtr induces ClpAP-mediated degradation of RpoS in Azotobacter vinelandii. Molecular microbiology 18 28097724
2014 Differential regulation of orphan nuclear receptor TR3 transcript variants by novel vascular growth factor signaling pathways. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 25016027