Affinage

TIGAR

Fructose-2,6-bisphosphatase TIGAR · UniProt Q9NQ88

Length
270 aa
Mass
30.1 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TIGAR is a p53-inducible histidine-phosphatase that reprograms central carbon metabolism to control redox balance and cell fate, originally identified as a gene that lowers fructose-2,6-bisphosphate to inhibit glycolysis, divert glucose into the pentose phosphate pathway, and suppress ROS-associated apoptosis (PMID:16839880). Structural and enzymatic work defined it as a histidine-phosphatase-fold bisphosphatase, and kinetic profiling established 2,3-bisphosphoglycerate as its highest-efficiency physiological substrate (~400-fold over fructose-2,6-bisphosphate) (PMID:19015259, PMID:24423178). The resulting NADPH/GSH output underlies a broad antioxidant program that restrains autophagy (PMID:19713938), protects proliferating intestinal cells from oxidative damage in cooperation with RAC1/NOX following APC loss (PMID:26679840), and confers ferroptosis and chemotherapy resistance in cancer (PMID:35271998). Layered on this enzymatic role is a set of phosphatase-independent activities: TIGAR translocates to mitochondria to bind and activate hexokinase 2 under hypoxia (PMID:23185017) and to inhibit succinate dehydrogenase via SDHA modification to limit reverse-electron-transfer ROS and ferroptosis during ischemia (PMID:38494143); it competes with NEMO for LUBAC binding to block NF-κB activation (PMID:29650758); it binds TAK1 in macrophages to promote TRAF6-mediated ubiquitination and amplify inflammatory signaling, with residues 152–161 forming the binding motif (PMID:38773142); and nuclear TIGAR acts as an NRF2 chromatin co-activator recruiting MLL1 and elongating Pol-II to antioxidant gene promoters (PMID:35847493). TIGAR also enforces p53-induced G1 arrest by promoting RB dephosphorylation and stabilizing the RB-E2F1 complex (PMID:22782351). Transcription is driven by SP1 and CREB at the proximal promoter and by p53/TCF19 complexes (PMID:21761199, PMID:24036271, PMID:34369624), while protein abundance is controlled by the E3 ubiquitin ligases TRIM31 and TRIM35 (PMID:34218200, PMID:35421414).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 High

    Established TIGAR's founding identity: a p53 target that links transcriptional stress responses to glycolytic control and ROS-dependent apoptosis.

    Evidence Microarray identification, siRNA knockdown with fructose-2,6-bisphosphate, ROS and apoptosis assays in cell lines

    PMID:16839880

    Open questions at the time
    • Did not define the direct enzymatic substrate or catalytic mechanism
    • Physiological vs. cancer-cell relevance of the glycolytic switch not resolved
  2. 2008 High

    Resolved the molecular basis of TIGAR activity by showing it is a histidine-phosphatase-fold enzyme that hydrolyzes bisphosphate sugars in vitro.

    Evidence X-ray crystallography of zebrafish TIGAR plus in vitro phosphatase assays on recombinant human and zebrafish protein

    PMID:19015259

    Open questions at the time
    • In vitro substrate panel did not rank physiological substrates by efficiency
    • No structure of human protein or substrate-bound complex
  3. 2014 High

    Reassigned the primary physiological substrate from fructose-2,6-bisphosphate to 2,3-bisphosphoglycerate based on catalytic efficiency and cellular metabolite levels.

    Evidence Quantitative in vitro kinetics against a phosphate-ester panel plus metabolite measurement in two genetic cell models

    PMID:24423178

    Open questions at the time
    • In vivo flux contribution of 2,3-BPG hydrolysis across tissues not quantified
    • Does not address non-enzymatic functions
  4. 2009 High

    Connected TIGAR's redox role to autophagy, showing it restrains stress-induced autophagy via ROS suppression rather than through mTOR.

    Evidence Knockdown/overexpression with LC3/autophagosome readouts, ROS measurement and mTOR pathway controls

    PMID:19713938

    Open questions at the time
    • Molecular link between ROS reduction and autophagy machinery left unspecified
  5. 2012 High

    Revealed a non-metabolic mitochondrial function: hypoxic TIGAR binds and activates hexokinase 2 to limit mitochondrial ROS, separable from its bisphosphatase activity.

    Evidence Subcellular fractionation, reciprocal Co-IP, HK2 activity assay and HIF1α inhibition in hypoxia models

    PMID:23185017

    Open questions at the time
    • Mechanism of HK2 activation by TIGAR binding not defined
    • Determinants of mitochondrial import unresolved
  6. 2012 Medium

    Extended TIGAR into cell-cycle control, showing it mediates p53-induced G1 arrest through RB dephosphorylation independent of p21.

    Evidence RB-E2F1 Co-IP, RB phosphorylation/CDK readouts, reporter assays and MCF-7 xenograft

    PMID:22782351

    Open questions at the time
    • Phosphatase whose activity dephosphorylates RB not identified
    • Single lab, no reciprocal validation of the RB-E2F1 mechanism
  7. 2015 Medium

    Linked TIGAR to the DNA damage response via PPP-derived NADPH/ribose and Cdk5-dependent ATM modulation, with stress-induced nuclear relocalization.

    Evidence Knockdown, Cdk5/ATM inhibition, γ-H2AX foci, NADPH/ribose rescue and nuclear fractionation

    PMID:25928429

    Open questions at the time
    • Mechanism of nuclear import not defined
    • Direct vs. indirect role in ATM signaling unclear
  8. 2019 Medium

    Identified TIGAR as a chromatin co-activator that physically partners with NRF2 to recruit MLL1 and Pol-II, an epigenetic role distinct from its enzymatic function.

    Evidence TIGAR-NRF2 Co-IP, ChIP for NRF2/MLL1/Pol-II at target genes, phosphatase-dead mutant and chemoresistance assays

    PMID:35847493

    Open questions at the time
    • How TIGAR is recruited to chromatin not established
    • Single lab
  9. 2018 High

    Defined a phosphatase-independent immune-signaling role: TIGAR competes with NEMO for LUBAC to block linear ubiquitination and NF-κB activation.

    Evidence Co-IP/binding competition with NEMO and LUBAC, phosphatase-dead mutant, NF-κB reporters and TIGAR KO/adipocyte-OE mice

    PMID:29650758

    Open questions at the time
    • Structural basis of NEMO/LUBAC competition not resolved
    • Generality across cell types beyond adipose untested
  10. 2024 High

    Showed a contrasting pro-inflammatory function in macrophages where TIGAR binds TAK1 via residues 152–161 to promote its ubiquitination and activation in sepsis.

    Evidence TIGAR-TAK1 Co-IP, motif mutagenesis, ubiquitination assay, phosphatase-dead control, myeloid-specific KO sepsis models and pharmacological disruption

    PMID:38773142

    Open questions at the time
    • Reconciliation with NF-κB-inhibitory LUBAC mechanism across cell types unresolved
  11. 2024 Medium

    Established a second mitochondrial enzyme-independent mechanism: ischemic TIGAR inhibits SDHA via acetylation/succinylation to suppress reverse-electron-transfer ROS and ferroptosis.

    Evidence TIGAR OE/KO in neurons, SDH activity assay, TIGAR-SDHA Co-IP, PTM analysis, ferroptosis markers and ischemia model

    PMID:38494143

    Open questions at the time
    • How TIGAR drives SDHA acetylation/succinylation mechanistically unknown
    • Single lab
  12. 2021 Medium

    Identified TRIM31 as an E3 ligase controlling TIGAR abundance through ubiquitin-proteasomal degradation in cerebral ischemia.

    Evidence TRIM31-TIGAR Co-IP, ubiquitination assay, proteasome rescue and TRIM31 KO mouse ischemia model

    PMID:34218200

    Open questions at the time
    • Ubiquitination site on TIGAR not mapped
    • Single lab
  13. 2022 Medium

    Identified a second degradative E3 ligase, TRIM35, linking TIGAR stability to mitochondrial fusion in renal ischemia-reperfusion.

    Evidence TRIM35-TIGAR Co-IP, ubiquitination assay, TIGAR KD rescue in renal IRI model

    PMID:35421414

    Open questions at the time
    • Whether TRIM31 and TRIM35 act redundantly or in distinct tissues unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TIGAR's opposing context-dependent roles—antioxidant protector versus injury amplifier, NF-κB inhibitor versus TAK1 activator—are selected within a given cell remains unresolved.
  • No unified model linking subcellular localization to functional output
  • Determinants of mitochondrial vs. nuclear vs. cytosolic partitioning unknown
  • Structural basis of competing protein-protein interactions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 3 GO:0140096 catalytic activity, acting on a protein 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005739 mitochondrion 3 GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-168256 Immune System 2 R-HSA-1640170 Cell Cycle 1
Partners
ATP5A1HK2NEMO/IKBKGNRF2/NFE2L2SDHATAK1/MAP3K7TRIM31TRIM35
Complex memberships
LUBAC (competitive binder)RB-E2F1 complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 TIGAR is a p53-inducible gene that functions to lower intracellular fructose-2,6-bisphosphate levels, thereby inhibiting glycolysis, increasing flux through the pentose phosphate pathway, reducing intracellular ROS, and protecting cells from ROS-associated apoptosis. Gene expression microarray identification, knockdown (siRNA), ROS measurement, fructose-2,6-bisphosphate assay, apoptosis assays in cell lines Cell High 16839880
2008 Crystal structure of zebrafish TIGAR reveals a histidine phosphatase fold with a catalytic histidine coordinating a phosphate molecule; the active site is open and positively charged. Recombinant human and zebrafish TIGAR hydrolyze fructose-2,6-bisphosphate and fructose-1,6-bisphosphate but not fructose-6-phosphate in vitro, confirming bisphosphatase activity. X-ray crystallography; in vitro phosphatase activity assays with recombinant human and zebrafish TIGAR The Journal of Biological Chemistry High 19015259
2009 TIGAR inhibits autophagy induced by nutrient starvation or metabolic stress by suppressing ROS levels; this inhibition is p53-independent and does not involve the mTOR pathway. Loss of TIGAR-induced autophagy moderates apoptosis by restraining ROS. TIGAR knockdown/overexpression, autophagy markers (LC3, autophagosome formation), ROS measurement, mTOR pathway analysis, nutrient starvation models The EMBO Journal High 19713938
2012 Under hypoxia, a fraction of TIGAR protein relocalizes to mitochondria and forms a complex with hexokinase 2 (HK2), resulting in increased HK2 activity. Mitochondrial localization depends on mitochondrial HK2 and HIF1α activity. The fructose-2,6-bisphosphatase activity of TIGAR is independent of HK2 binding and mitochondrial localization, but both activities cooperate to limit mitochondrial ROS and protect from cell death. Subcellular fractionation, Co-immunoprecipitation, HK2 activity assay, HIF1α inhibition, hypoxia cell culture models, cell death assays Proceedings of the National Academy of Sciences of the USA High 23185017
2014 TIGAR has the highest catalytic efficiency for 2,3-bisphosphoglycerate (2,3-BPG) among tested physiological substrates (~400-fold higher than for fructose-2,6-bisphosphate), and loss of TIGAR consistently increases cellular 2,3-BPG levels up to 5-fold, suggesting 2,3-BPG is the primary physiological substrate. In vitro phosphatase activity assays with recombinant human TIGAR against a panel of phosphate esters; genetic and shRNA-based cell culture models measuring metabolite levels The Biochemical Journal High 24423178
2012 TIGAR mediates p53-induced G1-phase cell-cycle arrest by promoting dephosphorylation of RB and stabilizing the RB-E2F1 complex, thereby inhibiting G1-to-S phase entry; this is p21-independent. Co-immunoprecipitation of RB-E2F1, RT-PCR, western blot, luciferase reporter assay, chromatin immunoprecipitation, MCF-7 xenograft tumor model British Journal of Cancer Medium 22782351
2015 TIGAR regulates DNA damage response through two mechanisms: (1) promoting NADPH/ribose production via the pentose phosphate pathway to support repair, and (2) modulating ATM phosphorylation through a Cdk5-dependent pathway. After genotoxic stress, TIGAR also relocates to the nucleus. TIGAR knockdown, pharmacological and siRNA inhibition of Cdk5 and ATM, γ-H2AX foci assay, NADPH/ribose supplementation rescue, nuclear fractionation Scientific Reports Medium 25928429
2018 TIGAR directly inhibits NF-κB signaling by competing with NEMO for binding to the linear ubiquitin assembly complex LUBAC, thereby preventing linear ubiquitination of NEMO and blocking IKKβ phosphorylation/activation. This function is independent of TIGAR's phosphatase activity, as a phosphatase-dead mutant is equally effective. Co-immunoprecipitation, direct binding competition assay with NEMO and LUBAC, phosphatase-dead TIGAR mutant, NF-κB reporter assays, TIGAR knockout mice (adipose tissue NF-κB signaling), adipocyte-specific TIGAR overexpression The Journal of Biological Chemistry High 29650758
2019 TIGAR promotes neural stem cell (NSC) differentiation by reducing glycolysis and increasing oxidative phosphorylation, leading to elevated acetyl-CoA levels and increased H3K9 acetylation at promoters of neuronal differentiation genes (Ngn1, Neurod1, Gfap). Acetate supplementation (precursor of acetyl-CoA) rescues NSC differentiation defects caused by TIGAR knockdown. TIGAR knockdown in cultured NSCs, acetyl-CoA measurement, ChIP for H3K9ac at gene promoters, acetate rescue experiment, metabolic flux analysis (oxygen consumption, lactate) Cell Death & Disease Medium 30814486
2019 TIGAR translocates to mitochondria in skeletal muscle during exhaustive exercise and interacts with ATP synthase F1 subunit α (ATP5A1), binding that increases during exhaustive exercise. Mitochondrial TIGAR promotes ATP generation, maintains mitochondrial membrane potential, and reduces mitochondrial oxidative stress under hypoxia. TIGAR also regulates mitochondrial biogenesis via the SIRT1-PGC1α deacetylation pathway. GST-TIGAR pulldown followed by liquid chromatography mass spectrometry (to identify ATP5A1 binding), subcellular fractionation, mitochondria-targeted TIGAR overexpression plasmid, TIGAR KO mice exhaustive swimming model, SIRT1-PGC1α pathway analysis FASEB Journal Medium 30726106
2021 The E3 ubiquitin ligase TRIM31 interacts with TIGAR, promotes its polyubiquitination, and targets it for proteasomal degradation, thereby reducing TIGAR protein levels during cerebral ischemia. Co-immunoprecipitation (TRIM31-TIGAR interaction), ubiquitination assay, proteasome inhibitor rescue, TRIM31 KO mouse model, TIGAR KD rescue experiments in ischemia model Redox Biology Medium 34218200
2022 A second E3 ubiquitin ligase, TRIM35, also interacts with TIGAR and promotes its polyubiquitination and proteasomal degradation; TRIM35 knockdown alleviates renal ischemia-reperfusion injury in part by stabilizing TIGAR and enhancing mitochondrial fusion. Co-immunoprecipitation (TRIM35-TIGAR interaction), ubiquitination assay, proteasome pathway inhibition, TIGAR KD rescue, renal IRI model International Journal of Biological Macromolecules Medium 35421414
2019 Nuclear TIGAR directly interacts with NRF2 and facilitates chromatin recruitment of NRF2, the H3K4me3 methylase MLL1, and elongating Pol-II to activate expression of NRF2 target genes (NQO1/2, PRDX1, GSTM4) and NSD2; this epigenetic co-activator function is independent of TIGAR's enzymatic phosphatase activity and confers cancer cell resistance to chemotherapy. Co-immunoprecipitation (TIGAR-NRF2 interaction), ChIP for NRF2/MLL1/Pol-II at target gene promoters, phosphatase-dead TIGAR mutant, nuclear localization studies, in vitro and in vivo chemotherapy resistance assays Acta Pharmaceutica Sinica B Medium 35847493
2024 Macrophage TIGAR directly binds to TGF-β-activated kinase 1 (TAK1) and promotes TRAF6-mediated ubiquitination and auto-phosphorylation of TAK1, thereby amplifying inflammatory signaling in sepsis. Residues 152–161 of TIGAR constitute a crucial binding motif, and this pro-inflammatory function is independent of TIGAR's phosphatase activity. Co-immunoprecipitation (TIGAR-TAK1 direct binding), ubiquitination assay, myeloid-specific Tigar knockout mice (LPS and CLP sepsis models), TIGAR motif mutagenesis, pharmacological disruption of TIGAR-TAK1 interaction (5Z-7-oxozeaenol) Nature Communications High 38773142
2024 Under prolonged ischemia, TIGAR translocates to mitochondria and inhibits succinate dehydrogenase (SDH) activity by interacting with SDHA and mediating post-translational modifications (acetylation and succinylation) of SDHA, thereby reducing ROS generation via the reverse electron transfer chain and decreasing neuronal ferroptosis. This mechanism is independent of the PPP-NADPH-GPX4 antioxidant pathway. TIGAR overexpression/KO in neurons, SDH activity assay, mitochondrial fractionation, Co-IP (TIGAR-SDHA), post-translational modification analysis (acetylation/succinylation), lipid peroxidation assay, ferroptosis markers, prolonged ischemia mouse model Free Radical Biology & Medicine Medium 38494143
2014 TIGAR expression in renal proximal straight tubules is induced by ischemia-reperfusion in a p53-dependent manner and inhibits phosphofructokinase-1 activity, depleting glycolytic ATP, with context-dependent effects: under mild ischemia TIGAR activates G6PD and raises NADPH/GSH (protective); under severe ischemia this protective response fails and TIGAR inhibition by siRNA is protective. siRNA knockdown of TIGAR in vivo and in vitro, PFK-1 activity assay, G6PD activity assay, NADPH/GSH measurement, functional/histological kidney injury readouts, p53-dependent induction shown by p53 inhibitor American Journal of Physiology. Renal Physiology Medium 25503731
2011 SP1 transcription factor binds the TIGAR promoter at a minimal region (-56/-4) and is indispensable for basal TIGAR transcription in liver cancer cells, as shown by EMSA and chromatin immunoprecipitation. 5'-RACE (transcription start site mapping), luciferase reporter with 5'-deletion constructs, EMSA, chromatin immunoprecipitation, SP1 knockdown Molecular and Cellular Biochemistry Medium 21761199
2013 CREB binds a cAMP-response element (CRE) at the TIGAR promoter region (-4/+13) and regulates TIGAR expression; CREB knockdown reduces TIGAR promoter activity and expression, while CREB overexpression or forskolin treatment enhances them. 5'-deletion and site-directed mutagenesis of TIGAR promoter-luciferase constructs, EMSA, chromatin immunoprecipitation, CREB knockdown and overexpression Biochemical and Biophysical Research Communications Medium 24036271
2021 TCF19 interacts with p53 and co-regulates TIGAR transcription; TCF19/p53 form complexes that include either CBP (activating) or HDAC1 (repressing) depending on glucose conditions, epigenetically programming TIGAR expression to control glycolysis and mitochondrial energy metabolism in hepatocytes. IP/MS (TCF19-p53 co-immunoprecipitation), ChIP for TCF19/p53/CBP/HDAC1 at TIGAR promoter, TCF19 and p53 knockdown, metabolic flux analysis (ECAR, OCR, ATP), RNA-seq FASEB Journal Medium 34369624
2015 TIGAR expression is induced independently of p53 and TAp73 in most mouse tissues in vivo, and mouse TIGAR is less responsive to p53 family members than human TIGAR; TIGAR induction in mouse intestine after ionizing radiation is also p53- and TAp73-independent. p53 KO mice, TAp73 KO mice, ionizing radiation in vivo, western blot for TIGAR in multiple mouse tissues Cell Death & Disease Medium 26247727
2019 TIGAR negatively regulates BRCA1 and the Fanconi anemia pathway; TIGAR knockdown enhances sensitivity to the PARP inhibitor olaparib by downregulating these DNA repair components and increasing cellular senescence. Genome-scale CRISPR/Cas9 knockout screen, TIGAR KD in cancer cells, BRCA1 and Fanconi anemia pathway western blot, olaparib sensitivity assays, senescence assays Communications Biology Medium 31508509
2017 TIGAR promotes NSCLC cell invasion and metastasis via a Met signaling pathway; Met expression positively correlates with TIGAR in NSCLC, and TIGAR knockdown reduces invasion/metastasis in vitro and in vivo. TIGAR knockdown/overexpression, Transwell invasion assays, in vivo metastasis model, immunohistochemistry for TIGAR and Met in patient samples, Met inhibitor experiments Molecular Cancer Low 29753331
2021 SIRT3 regulates TIGAR expression in cardiomyocytes by deacetylating p53; high glucose increases p53 acetylation, which drives TIGAR upregulation and suppresses glycolysis. SIRT3 overexpression reduces p53 acetylation and TIGAR expression, restoring glycolysis and reducing ROS and apoptosis under hyperglycemic conditions. SIRT3 overexpression (adenovirus) and TIGAR siRNA in H9c2 cells, p53 acetylation western blot, glycolysis (ECAR) measurement, PFKFB3 expression, db/db diabetic mouse model in vivo Journal of the American Heart Association Medium 33586458
2022 TIGAR confers ferroptosis resistance in colorectal cancer cells via a ROS/AMPK/SCD1 signaling pathway; TIGAR knockdown increases lipid peroxidation, decreases GSH/GSSG ratio, and reduces SCD1 expression in a redox- and AMPK-dependent manner. TIGAR knockdown in CRC cells, erastin-induced ferroptosis assay, GSH/GSSG ratio, lipid peroxidation (MDA), AMPK and SCD1 western blot, antioxidant rescue Free Radical Biology & Medicine Medium 35271998
2016 Following APC/Wnt pathway activation, TIGAR and RAC1/NOX generate opposing ROS signals in the same intestinal cell: TIGAR limits damaging ROS while RAC1/NOX generates pro-proliferative ROS. Loss of TIGAR increases oxidative damage and inhibits proliferation; TIGAR and RAC1 cooperate to maintain optimal intestinal proliferation after APC loss. TIGAR KO mice, APC deletion mouse model, 3D intestinal organoid cultures, ROS measurement, NOX inhibition, genetic epistasis (TIGAR KO × RAC1 KO double mutants) Genes & Development High 26679840
2014 TIGAR ischemia/reperfusion upregulation in brain is mediated by the transcription factor SP1; ROS (H2O2) and stress hormones (adrenaline, hydrocortisone, glucagon) induce TIGAR protein, while insulin suppresses it. SP1 knockdown or inhibition blocks ischemia-induced TIGAR upregulation. SP1 siRNA, mithramycin A inhibition, SP1 ChIP at TIGAR promoter, tMCAO/R mouse model, OGD/R in HT22 cells and primary neurons, hormone and glucose treatments Neurochemistry International Medium 25445985
2022 Under prolonged ischemia (PPP impaired), TIGAR induces autophagy which activates Nrf2, providing an alternative antioxidant mechanism independent of PPP/NADPH. Genetic deletion of Atg7 or Nrf2 abolishes TIGAR neuroprotection in prolonged ischemia. PPP inhibition (G6PD knockdown), catalytically-inactive TIGAR mutant expression, Atg7 KO, Nrf2 KO, mouse prolonged ischemia model, ROS and neuronal survival assays Redox Biology Medium 35576689
2019 TIGAR knockdown in cancer cells decreases BRCA1 and Fanconi anemia pathway components, increases senescence, and sensitizes cells to PARP inhibitor olaparib; this identifies TIGAR as a modifier of homologous recombination capacity. CRISPR/Cas9 genome-scale screen (identification), TIGAR KD, BRCA1 western blot, olaparib sensitivity, senescence assay Communications Biology Medium 31508509

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 1636 16839880
2009 Modulation of intracellular ROS levels by TIGAR controls autophagy. The EMBO journal 309 19713938
2006 p53 and metabolism: Inside the TIGAR. Cell 199 16839873
2020 Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer. Cancer cell 197 31983610
2012 Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death. Proceedings of the National Academy of Sciences of the United States of America 197 23185017
2013 TIGAR is required for efficient intestinal regeneration and tumorigenesis. Developmental cell 162 23726973
2012 Tp53-induced glycolysis and apoptosis regulator (TIGAR) protects glioma cells from starvation-induced cell death by up-regulating respiration and improving cellular redox homeostasis. The Journal of biological chemistry 138 22887998
2015 MiR-144 inhibits proliferation and induces apoptosis and autophagy in lung cancer cells by targeting TIGAR. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 103 25660220
2014 A TIGAR-regulated metabolic pathway is critical for protection of brain ischemia. The Journal of neuroscience : the official journal of the Society for Neuroscience 97 24872551
2008 Structural and biochemical studies of TIGAR (TP53-induced glycolysis and apoptosis regulator). The Journal of biological chemistry 95 19015259
2022 TIGAR drives colorectal cancer ferroptosis resistance through ROS/AMPK/SCD1 pathway. Free radical biology & medicine 93 35271998
2014 TIGAR, TIGAR, burning bright. Cancer & metabolism 90 24383451
2011 Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human breast cancer. Human pathology 90 21820150
2019 TIGAR alleviates ischemia/reperfusion-induced autophagy and ischemic brain injury. Free radical biology & medicine 89 30978385
2019 TIGAR: An Improved Bayesian Tool for Transcriptomic Data Imputation Enhances Gene Mapping of Complex Traits. American journal of human genetics 89 31230719
2015 Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine. Genes & development 88 26679840
2011 Inhibition of the MUC1-C oncoprotein induces multiple myeloma cell death by down-regulating TIGAR expression and depleting NADPH. Blood 84 22117045
2014 TIGAR has a dual role in cancer cell survival through regulating apoptosis and autophagy. Cancer research 71 25085248
2019 TIGAR promotes neural stem cell differentiation through acetyl-CoA-mediated histone acetylation. Cell death & disease 67 30814486
2016 TP53-inducible Glycolysis and Apoptosis Regulator (TIGAR) Metabolically Reprograms Carcinoma and Stromal Cells in Breast Cancer. The Journal of biological chemistry 67 27803158
2021 Sirtuin 3 Alleviates Diabetic Cardiomyopathy by Regulating TIGAR and Cardiomyocyte Metabolism. Journal of the American Heart Association 66 33586458
2011 TP53 induced glycolysis and apoptosis regulator (TIGAR) knockdown results in radiosensitization of glioma cells. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 65 21864926
2021 Structure, regulation, and biological functions of TIGAR and its role in diseases. Acta pharmacologica Sinica 63 33510458
2010 p53 and TIGAR regulate cardiac myocyte energy homeostasis under hypoxic stress. American journal of physiology. Heart and circulatory physiology 59 20935145
2015 TIGAR regulates DNA damage and repair through pentosephosphate pathway and Cdk5-ATM pathway. Scientific reports 57 25928429
2014 Targeting MUC1-C is synergistic with bortezomib in downregulating TIGAR and inducing ROS-mediated myeloma cell death. Blood 56 24632713
2017 Targeting MUC1-C inhibits the AKT-S6K1-elF4A pathway regulating TIGAR translation in colorectal cancer. Molecular cancer 55 28153010
2019 Urolithin A gains in antiproliferative capacity by reducing the glycolytic potential via the p53/TIGAR axis in colon cancer cells. Carcinogenesis 52 30418550
2014 TIGAR regulates glycolysis in ischemic kidney proximal tubules. American journal of physiology. Renal physiology 52 25503731
2010 Inhibition of c-Met downregulates TIGAR expression and reduces NADPH production leading to cell death. Oncogene 52 21057531
2019 Potent effects of dioscin against hepatocellular carcinoma through regulating TP53-induced glycolysis and apoptosis regulator (TIGAR)-mediated apoptosis, autophagy, and DNA damage. British journal of pharmacology 49 30710454
2018 TIGAR inhibits ischemia/reperfusion-induced inflammatory response of astrocytes. Neuropharmacology 49 29331305
2012 TIGAR induces p53-mediated cell-cycle arrest by regulation of RB-E2F1 complex. British journal of cancer 49 22782351
2022 TIGAR alleviates oxidative stress in brain with extended ischemia via a pentose phosphate pathway-independent manner. Redox biology 48 35576689
2021 The E3 ubiquitin ligase TRIM31 is involved in cerebral ischemic injury by promoting degradation of TIGAR. Redox biology 48 34218200
2017 TIGAR mediates the inhibitory role of hypoxia on ROS production and apoptosis in rat nucleus pulposus cells. Osteoarthritis and cartilage 47 29061494
2016 TIGAR contributes to ischemic tolerance induced by cerebral preconditioning through scavenging of reactive oxygen species and inhibition of apoptosis. Scientific reports 47 27256465
2019 TP53, TP53 Target Genes (DRAM, TIGAR), and Autophagy. Advances in experimental medicine and biology 45 31776983
2018 Loss of TIGAR Induces Oxidative Stress and Meiotic Defects in Oocytes from Obese Mice. Molecular & cellular proteomics : MCP 45 29776966
2015 Resveratrol inhibits TIGAR to promote ROS induced apoptosis and autophagy. Biochimie 42 26212201
2018 Met is involved in TIGAR-regulated metastasis of non-small-cell lung cancer. Molecular cancer 40 29753331
2019 TIGAR Attenuates High Glucose-Induced Neuronal Apoptosis via an Autophagy Pathway. Frontiers in molecular neuroscience 39 31456661
2019 Genome-scale CRISPR knockout screen identifies TIGAR as a modifier of PARP inhibitor sensitivity. Communications biology 39 31508509
2018 The diverse role of TIGAR in cellular homeostasis and cancer. Free radical research 39 30284488
2013 Knockdown of TIGAR by RNA interference induces apoptosis and autophagy in HepG2 hepatocellular carcinoma cells. Biochemical and biophysical research communications 39 23817040
2021 NF-κB-Induced Upregulation of miR-146a-5p Promoted Hippocampal Neuronal Oxidative Stress and Pyroptosis via TIGAR in a Model of Alzheimer's Disease. Frontiers in cellular neuroscience 38 33935653
2014 Identification of TP53-induced glycolysis and apoptosis regulator (TIGAR) as the phosphoglycolate-independent 2,3-bisphosphoglycerate phosphatase. The Biochemical journal 37 24423178
2014 Ischemia/reperfusion-induced upregulation of TIGAR in brain is mediated by SP1 and modulated by ROS and hormones involved in glucose metabolism. Neurochemistry international 37 25445985
2013 ATM-NFκB axis-driven TIGAR regulates sensitivity of glioma cells to radiomimetics in the presence of TNFα. Cell death & disease 37 23640457
2020 Metabolic remodeling by TIGAR overexpression is a therapeutic target in esophageal squamous-cell carcinoma. Theranostics 36 32206103
2013 Two p53-related metabolic regulators, TIGAR and SCO2, contribute to oroxylin A-mediated glucose metabolism in human hepatoma HepG2 cells. The international journal of biochemistry & cell biology 36 23612020
2019 TIGAR regulates mitochondrial functions through SIRT1-PGC1α pathway and translocation of TIGAR into mitochondria in skeletal muscle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 35 30726106
2017 Downregulation of TIGAR sensitizes the antitumor effect of physapubenolide through increasing intracellular ROS levels to trigger apoptosis and autophagosome formation in human breast carcinoma cells. Biochemical pharmacology 34 28774732
2021 TIGAR-V2: Efficient TWAS tool with nonparametric Bayesian eQTL weights of 49 tissue types from GTEx V8. HGG advances 33 35047855
2021 Decitabine Downregulates TIGAR to Induce Apoptosis and Autophagy in Myeloid Leukemia Cells. Oxidative medicine and cellular longevity 32 33532040
2019 TIGAR impedes compression-induced intervertebral disc degeneration by suppressing nucleus pulposus cell apoptosis and autophagy. Journal of cellular physiology 29 31317559
2015 p53- and p73-independent activation of TIGAR expression in vivo. Cell death & disease 29 26247727
2024 TIGAR reduces neuronal ferroptosis by inhibiting succinate dehydrogenase activity in cerebral ischemia. Free radical biology & medicine 28 38494143
2021 TCF19 and p53 regulate transcription of TIGAR and SCO2 in HCC for mitochondrial energy metabolism and stress adaptation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 34369624
2019 LKB1/p53/TIGAR/autophagy-dependent VEGF expression contributes to PM2.5-induced pulmonary inflammatory responses. Scientific reports 27 31719630
2013 TIGAR: transcript isoform abundance estimation method with gapped alignment of RNA-Seq data by variational Bayesian inference. Bioinformatics (Oxford, England) 27 23821651
2023 Dimethyl fumarate ameliorates parkinsonian pathology by modulating autophagy and apoptosis via Nrf2-TIGAR-LAMP2/Cathepsin D axis. Brain research 26 37315723
2021 TIGAR mitigates atherosclerosis by promoting cholesterol efflux from macrophages. Atherosclerosis 26 33994201
2023 TIGAR deficiency induces caspase-1-dependent trophoblasts pyroptosis through NLRP3-ASC inflammasome. Frontiers in immunology 25 37122710
2019 TIGAR Promotes Tumorigenesis and Protects Tumor Cells From Oxidative and Metabolic Stresses in Gastric Cancer. Frontiers in oncology 25 31799200
2018 The ER-alpha mutation Y537S confers Tamoxifen-resistance via enhanced mitochondrial metabolism, glycolysis and Rho-GDI/PTEN signaling: Implicating TIGAR in somatic resistance to endocrine therapy. Aging 25 30573703
2017 TIGAR knockdown radiosensitizes TrxR1-overexpressing glioma in vitro and in vivo via inhibiting Trx1 nuclear transport. Scientific reports 24 28338004
2022 Ginsenoside Rg3 induces apoptosis and inhibits proliferation by down-regulating TIGAR in rats with gastric precancerous lesions. BMC complementary medicine and therapies 23 35840932
2015 Endogenous level of TIGAR in brain is associated with vulnerability of neurons to ischemic injury. Neuroscience bulletin 23 26219221
2010 An RNA-directed nucleoside anti-metabolite, 1-(3-C-ethynyl-beta-d-ribo-pentofuranosyl)cytosine (ECyd), elicits antitumor effect via TP53-induced Glycolysis and Apoptosis Regulator (TIGAR) downregulation. Biochemical pharmacology 22 20219441
2020 TP53-induced glycolysis and apoptosis regulator (TIGAR) ameliorates lysosomal damage in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-mediated mouse model of Parkinson's disease. Toxicology letters 21 33359019
2019 Ablation of cardiac TIGAR preserves myocardial energetics and cardiac function in the pressure overload heart failure model. American journal of physiology. Heart and circulatory physiology 21 30901275
2019 TIGAR promotes growth, survival and metastasis through oxidation resistance and AKT activation in glioblastoma. Oncology letters 21 31402948
2016 Distinctive interrelation of p53 with SCO2, COX, and TIGAR in human gastric cancer. Pathology, research and practice 21 27499152
2020 TIGAR reduces smooth muscle cell autophagy to prevent pulmonary hypertension. American journal of physiology. Heart and circulatory physiology 20 32946259
2018 The fructose-2,6-bisphosphatase TIGAR suppresses NF-κB signaling by directly inhibiting the linear ubiquitin assembly complex LUBAC. The Journal of biological chemistry 20 29650758
2018 TIGAR knockdown enhanced the anticancer effect of aescin via regulating autophagy and apoptosis in colorectal cancer cells. Acta pharmacologica Sinica 20 29769743
2013 TIGAR is correlated with maximal standardized uptake value on FDG-PET and survival in non-small cell lung cancer. PloS one 20 24363807
2011 SP1 plays a pivotal role for basal activity of TIGAR promoter in liver cancer cell lines. Molecular and cellular biochemistry 20 21761199
2021 Targeting neuroinflammation to treat cerebral ischemia - The role of TIGAR/NADPH axis. Neurochemistry international 19 34082063
2021 Nuclear TIGAR mediates an epigenetic and metabolic autoregulatory loop via NRF2 in cancer therapeutic resistance. Acta pharmaceutica Sinica. B 19 35847493
2019 Knockdown of the TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Sensitizes Glioma Cells to Hypoxia, Irradiation and Temozolomide. International journal of molecular sciences 19 30823646
2019 Down-regulation of TFAM increases the sensitivity of tumour cells to radiation via p53/TIGAR signalling pathway. Journal of cellular and molecular medicine 19 31062473
2019 IDH1-R132H mutation radiosensitizes U87MG glioma cells via epigenetic downregulation of TIGAR. Oncology letters 19 31966064
2024 Disruption of TIGAR-TAK1 alleviates immunopathology in a murine model of sepsis. Nature communications 18 38773142
2016 Akt mediates TIGAR induction in HeLa cells following PFKFB3 inhibition. FEBS letters 18 27491040
2022 Cordycepin exhibits anti-fatigue effect via activating TIGAR/SIRT1/PGC-1α signaling pathway. Biochemical and biophysical research communications 17 36399798
2017 Hypoxia-induced hsa-miR-101 promotes glycolysis by targeting TIGAR mRNA in clear cell renal cell carcinoma. Molecular medicine reports 17 28138701
2008 Identification of TIGAR in the equilibrative nucleoside transporter 2-mediated response to fludarabine in chronic lymphocytic leukemia cells. Haematologica 17 18945750
2018 The human T-cell leukemia virus type-1 p30II protein activates p53 and induces the TIGAR and suppresses oncogene-induced oxidative stress during viral carcinogenesis. Virology 16 29462755
2020 Dynamic ROS Regulation by TIGAR: Balancing Anti-cancer and Pro-metastasis Effects. Cancer cell 15 32049042
2019 miR-885-5p plays an accomplice role in liver cancer by instigating TIGAR expression via targeting its promoter. Biotechnology and applied biochemistry 14 31119791
2013 CREB, another culprit for TIGAR promoter activity and expression. Biochemical and biophysical research communications 14 24036271
2022 MiR-652-5p elevated glycolysis level by targeting TIGAR in T-cell acute lymphoblastic leukemia. Cell death & disease 13 35165280
2022 The inhibition of TRIM35-mediated TIGAR ubiquitination enhances mitochondrial fusion and alleviates renal ischemia-reperfusion injury. International journal of biological macromolecules 13 35421414
2021 Metformin regulates the Th17/Treg balance by glycolysis with TIGAR in hepatic ischemia-reperfusion injury. Journal of pharmacological sciences 13 33858654
2020 microRNA-144 inhibits cell proliferation and invasion by directly targeting TIGAR in esophageal carcinoma. Oncology letters 12 32256808
2020 TIGAR/AP-1 axis accelerates the division of Lgr5- reserve intestinal stem cells to reestablish intestinal architecture after lethal radiation. Cell death & disease 12 32632140
2019 TIGAR suppresses seizures induced by kainic acid through inhibiting oxidative stress and neuronal apoptosis. Biochemical and biophysical research communications 12 31160088
2024 TIGAR relieves PCOS by inhibiting granulosa cell apoptosis and oxidative stress through activating Nrf2. Molecular and cellular endocrinology 11 39341450

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