Affinage

TPI1

Triosephosphate isomerase · UniProt P60174

Round 2 corrected
Length
249 aa
Mass
26.7 kDa
Annotated
2026-04-28
67 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TPI1 encodes the homodimeric glycolytic enzyme triosephosphate isomerase that interconverts dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP), and its catalytic activity is tuned by post-translational modifications including LKB1/SIK-dependent phosphorylation at Ser21 (which partitions flux between glycolysis and glycerol-lipid synthesis) and dopaminylation at Q65 (which directionally enhances DHAP→GAP conversion to suppress ferroptosis) (PMID:36715544, PMID:39111287). Beyond cytoplasmic glycolysis, stress- and kinase-driven nuclear translocation of TPI1 alters histone acetylation landscapes—lowering nuclear DHAP elevates H3K27ac at select promoters and, in complex with PKM2, increases H3K4 acetylation—linking TPI1 to transcriptional reprogramming, chemoresistance, and salt-sensitive hypertension (PMID:35246510, PMID:39342418, PMID:41407053). Non-catalytic protein–protein interactions extend TPI1's functions: it binds Beclin-1 to competitively displace Bcl-2 and activate autophagy, and scaffolds an AKT–MDM2 complex to promote p53 ubiquitination, while its stability is controlled by USP5-mediated deubiquitination and SQSTM1/P62-promoted proteasomal degradation (PMID:41429797, PMID:40097123, PMID:40956511, PMID:35509067). Disease-causing missense mutations such as Arg189Gln and R5G destabilize the dimer and reduce steady-state protein levels rather than abolishing catalytic competence per se, establishing protein instability as the primary pathogenic mechanism in TPI deficiency (PMID:31075491, PMID:41153421).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1979 High

    Mapping TPI1 to chromosome 12p established the gene's chromosomal locus, enabling subsequent molecular genetic studies of TPI deficiency.

    Evidence Somatic cell hybrid panel with karyotypic correlation of isozyme markers

    PMID:477403

    Open questions at the time
    • No coding sequence or promoter characterization at this stage
    • Regulatory elements and tissue-specific expression uncharacterized
  2. 2019 High

    Structural analysis of the Arg189Gln mutation revealed that dimer-interface salt bridges are critical for protein stability rather than catalysis per se, explaining why pathogenic mutations reduce enzyme levels in vivo and cause neurologic deficits.

    Evidence Drosophila genomic engineering of homologous Arg mutation, patient fibroblast protein quantification, and structural modeling of dimer interface

    PMID:31075491

    Open questions at the time
    • Mechanism linking reduced TPI levels to neurodegeneration unresolved
    • Whether all disease alleles act through instability or some affect catalysis differently
  3. 2022 Medium

    Discovery that TPI1 nuclear translocation—independent of its catalytic activity—drives oncogenic function and chemoresistance opened a non-glycolytic axis for TPI1 biology.

    Evidence Catalytic-dead mutants, subcellular fractionation, and xenograft models in lung adenocarcinoma

    PMID:35246510

    Open questions at the time
    • Nuclear substrates or transcriptional targets of TPI1 not identified in this study
    • Signal triggering nuclear import not molecularly defined
  4. 2022 Medium

    Identification of SQSTM1/P62 as a ubiquitin-dependent degradation promoter and CDCA5 as a stabilization partner of TPI1 linked TPI1 protein turnover and PI3K/AKT/mTOR signaling in breast cancer.

    Evidence Reciprocal Co-IP, ubiquitination assays, and xenograft models

    PMID:35509067

    Open questions at the time
    • E3 ligase mediating TPI1 ubiquitination not identified
    • Whether CDCA5 stabilization requires direct binding or is indirect
  5. 2023 High

    Phosphoproteomics resolved how LKB1 controls glycolytic vs. lipid-synthetic flux through SIK-mediated phosphorylation of TPI1 at Ser21, while revealing an evolutionary divergence (Cys21 oxidation in mice) in TPI1 regulation.

    Evidence Phosphoproteomics, metabolomics, site-directed mutagenesis in human cells and genetically engineered mouse models

    PMID:36715544

    Open questions at the time
    • Structural basis for how Ser21 phosphorylation alters catalytic directionality unresolved
    • Whether other kinases phosphorylate Ser21 outside LKB1-deficient contexts
  6. 2024 High

    Dopaminylation at Q65 was shown to directionally enhance DHAP→GAP conversion, directly linking a novel post-translational modification to ferroptosis suppression and lung tissue regeneration.

    Evidence Chemoproteomic identification of dopaminylation site, Q65 mutagenesis, metabolic flux analysis, and in vivo lung injury models

    PMID:39111287

    Open questions at the time
    • Enzyme(s) catalyzing TPI1 dopaminylation not identified
    • Reversibility and kinetics of dopaminylation unknown
  7. 2024 Medium

    Nuclear TPI1, in complex with PKM2 recruited by lncRNA Linc00942, was found to increase H3K4 acetylation and activate STAT3/P300-dependent SOX9 transcription, mechanistically connecting TPI1 nuclear function to epigenetic reprogramming and temozolomide resistance in glioblastoma.

    Evidence ChIRP-MS/WB for Linc00942–TPI1/PKM2 interaction, Co-IP, nuclear fractionation, SOX9 knockdown rescue in vitro and in vivo

    PMID:39342418

    Open questions at the time
    • Whether TPI1 directly contacts chromatin or acts solely through protein–protein scaffolding
    • Generalizability beyond GBM not tested
  8. 2024 Medium

    Epigenetic feed-forward regulation was demonstrated: LDHA-generated lactate drives H3K18 lactylation at the TPI1 promoter to upregulate TPI1 transcription, creating a positive glycolytic loop.

    Evidence H3K18la ChIP at TPI1 promoter, K69 mutagenesis, LDHA knockout mouse model of osteoarthritis

    PMID:39086231

    Open questions at the time
    • Whether H3K18la-driven TPI1 upregulation operates in non-inflammatory contexts
    • Relative contribution vs. other transcriptional regulators of TPI1
  9. 2025 Medium

    The non-catalytic interaction between TPI1 and Beclin-1's BH3 domain, which displaces Bcl-2 to activate autophagy initiation, established TPI1 as a direct modulator of the autophagy machinery and explained gemcitabine resistance in bladder cancer.

    Evidence MS-identified interaction, Co-IP with domain mapping, ULK1 phosphorylation readouts, xenograft models

    PMID:41429797

    Open questions at the time
    • Structural basis for TPI1–Beclin-1 BH3 domain recognition unknown
    • Whether this interaction occurs under physiological (non-cancer) conditions
  10. 2025 Medium

    TPI1 scaffolds AKT and MDM2 into a trimeric complex to promote p53 degradation, revealing a second non-catalytic oncogenic mechanism distinct from its autophagy and epigenetic roles.

    Evidence Co-IP, MDM2 truncation domain mapping (residues 181–360, critical aa 317), AKT knockdown rescue, ubiquitination assays

    PMID:40097123

    Open questions at the time
    • Whether TPI1–MDM2 binding is direct or bridged by AKT
    • Relevance outside bladder cancer models not tested
  11. 2025 Medium

    GRK4-mediated phosphorylation was shown to drive TPI1 nuclear translocation in renal tubular cells, lowering nuclear DHAP and elevating H3K27ac at the Hao2 promoter, mechanistically linking TPI1 to salt-sensitive hypertension and renal oxidative stress.

    Evidence IP-MS for GRK4–TPI1 interaction, AAV9-mediated GRK4 depletion, H3K27ac ChIP at Hao2 promoter, DHAP supplementation rescue, GRK4 R65L transgenic mice

    PMID:41407053

    Open questions at the time
    • Specific TPI1 phosphorylation site(s) by GRK4 not mapped
    • Whether nuclear TPI1 directly binds chromatin or only modulates metabolite pools
  12. 2025 Medium

    USP5 was identified as the deubiquitinase that stabilizes TPI1, closing a gap in understanding TPI1 protein turnover and providing a druggable axis in lung cancer.

    Evidence Ubiquitination analysis, Co-IP, propofol treatment, xenograft models

    PMID:40956511

    Open questions at the time
    • Specific ubiquitin chain type removed by USP5 unknown
    • Whether USP5 is the sole or dominant TPI1 deubiquitinase
  13. 2025 Medium

    Biochemical characterization of the R5G disease allele confirmed that protein instability (not loss of catalytic competence) is the primary pathogenic mechanism, and small molecules can rescue TPI1 protein levels in patient cells.

    Evidence Purified recombinant TPIR5G kinetics, Western blot of patient fibroblasts, small-molecule rescue screen

    PMID:41153421

    Open questions at the time
    • In vivo efficacy and CNS penetration of stabilizing compounds not tested
    • Whether stabilizers work across diverse TPI deficiency alleles

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and cell-biological model explaining how TPI1 partitions between cytoplasmic glycolysis, nuclear translocation, and non-catalytic protein scaffolding—and how these functions are coordinately regulated—remains unresolved.
  • No crystal structure of post-translationally modified (phospho-Ser21, dopaminyl-Q65) TPI1
  • Nuclear import signal and receptor for TPI1 translocation unidentified
  • Relative quantitative contribution of non-catalytic vs. catalytic functions in normal physiology unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016853 isomerase activity 4 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 2 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
AKT1BECN1CDCA5GRK4MDM2PKMSQSTM1USP5

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 TPI1 nuclear translocation (rather than its cytoplasmic glycolytic activity) drives oncogenic function in lung adenocarcinoma; nuclear accumulation is induced by extracellular stress such as chemotherapy agents and peroxide, facilitating chemoresistance. Knockdown/overexpression of TPI1, catalytic-dead mutants, subcellular fractionation, xenograft tumor models, IHC of clinical LUAD vs. adjacent normal tissue Cell death & disease Medium 35246510
2023 In human lung adenocarcinoma, TPI1 activity is regulated by phosphorylation at Ser21 by salt-inducible kinases (SIKs) in an LKB1-dependent manner, modulating metabolic flux between glycolysis completion and glycerol-lipid production. In mice, the equivalent residue is Cys21, which can be oxidized to alter TPI1 activity independently of SIKs/LKB1, revealing an evolutionary divergence in TPI1 regulation. Phosphoproteomics, metabolomics, site-directed mutagenesis, genetically engineered human cell lines and mouse models (GEMM) Cancer discovery High 36715544
2024 Dopaminylation of glutamine 65 (Q65) of TPI1 in endothelial cells directionally enhances TPI1's enzymatic activity to convert DHAP to GAP, shifting flux away from ether phospholipid synthesis toward glucose metabolism, thereby attenuating lipid peroxidation and suppressing ferroptosis to promote lung regeneration over fibrosis. Chemoproteomic identification of dopaminylation site, site-directed mutagenesis (Q65), metabolic flux analysis, ferroptosis assays, in vivo lung injury/fibrosis models Cell metabolism High 39111287
2022 TPI1 interacts with SQSTM1/P62, and P62 promotes ubiquitin-dependent proteasomal degradation of TPI1 in breast cancer cells. TPI1 also interacts with CDCA5 to stabilize it, activating the PI3K/AKT/mTOR pathway and driving EMT and aerobic glycolysis. Co-IP, mass spectrometric analysis, ubiquitination assay, immunofluorescence, overexpression/knockdown in cells and mouse xenograft models Journal of translational medicine Medium 35509067
2021 Rab20 downregulation in hepatocellular carcinoma reduces TPI1 loading into extracellular vesicles; EVs with reduced TPI1 enhance aerobic glycolysis and promote HCC cell growth and motility, establishing a mechanistic link between EV-associated TPI1 and tumor glucose metabolism. Proteomic profiling of EVs, Rab20 knockdown/restoration, TPI1 knockdown, glycolytic inhibitor rescue experiments, motility and growth assays Journal of extracellular vesicles Medium 34401050
2019 The Arg189 residue of TPI1 participates in two salt bridges on the backside of the enzyme dimer interface; mutation at this position (Arg189Gln) disrupts coordination of the substrate-binding site and key catalytic residues, markedly reducing protein stability and enzyme levels in vivo and causing neurologic deficits. Genomic engineering in Drosophila (homologous Arg mutation), compound heterozygote animal motor behavior assays, patient fibroblast protein quantification, structural analysis of dimer interface salt bridges Biochimica et biophysica acta. Molecular basis of disease High 31075491
2025 TPI1 directly binds the BH3 domain of Beclin-1, competitively displacing Bcl-2 from Beclin-1 and relieving Bcl-2-mediated inhibition of autophagy initiation; this interaction promotes PIK3C3-C1 complex formation, enhances ULK1-mediated phosphorylation of Beclin-1 at Ser15, and drives gemcitabine resistance in bladder cancer. Mass spectrometry, co-immunoprecipitation, transcriptome sequencing, transmission electron microscopy, dual luciferase/ChIP-qPCR for c-Myc binding to TPI1 promoter, in vivo xenograft models Cell death & disease Medium 41429797
2025 TPI1 interacts with AKT and MDM2 to form a trimeric complex; TPI1 enhances AKT-driven phosphorylation of MDM2 at Ser166, promoting p53 ubiquitination and degradation in bladder cancer. The MDM2-F2 truncation (residues 181–360) binds TPI1, with amino acid 317 being critical for this interaction. Co-IP, domain-mapping with MDM2 truncation mutants, AKT knockdown rescue, ubiquitination assays, in vitro and in vivo functional assays Pharmacological research Medium 40097123
2024 LDHA-mediated histone H3K18 lactylation (H3K18la) at the TPI1 promoter enhances TPI1 transcription; mutation of K69 in TPI1 ameliorates LPS-induced glycolysis in an OA chondrocyte cell model, identifying a direct epigenetic regulatory link between lactate metabolism and TPI1 expression. LDHA knockdown, H3K18la ChIP at TPI1 promoter, site-directed mutagenesis of TPI1 (K69), glycolysis assays, in vivo LDHA knockout OA mouse model Autoimmunity Medium 39086231
2025 In the context of salt-sensitive hypertension, GRK4 R65L increases TPI1 phosphorylation and promotes its nuclear translocation; nuclear TPI1 reduces DHAP levels, which elevates H3K27ac at the Hao2 promoter, increasing Hao2 expression and renal oxidative stress, thereby causing a rightward shift in pressure-natriuresis and salt-sensitive hypertension. Immunoprecipitation-mass spectrometry (GRK4–TPI1 interaction), AAV9-mediated GRK4 depletion, measurement of nuclear DHAP, H3K27ac ChIP at Hao2 promoter, DHAP supplementation in HK-2 cells, GRK4 R65L transgenic mice Free radical biology & medicine Medium 41407053
2025 USP5 deubiquitinase stabilizes TPI1 protein by removing its ubiquitin modifications; propofol increases TPI1 ubiquitination and reduces TPI1 protein stability, suppressing glycolysis and lung cancer progression through this USP5/TPI1 axis. Ubiquitination analysis, Co-IP, Western blot, xenograft in vivo models, glycolysis assays, STRING interaction database validation Biochemical genetics Medium 40956511
2025 TPI1 silencing in cisplatin-resistant oral squamous cell carcinoma increases intracellular ROS, free iron, and lipid peroxidation, promoting ferroptotic cell death; TPI1 overexpression protects cells from ferroptosis, establishing TPI1 as a regulator of ferroptosis sensitivity. TPI1 knockdown/overexpression in cisplatin-resistant OSCC lines, measurement of lipid ROS, free iron, and lipid peroxidation markers, in vivo xenograft models, ferroptosis-related gene expression analysis Biomedicines Medium 40427052
2024 The lncRNA Linc00942 (Linc00942) interacts with TPI1 and PKM2, promoting their phosphorylation, dimerization, and nuclear translocation; nuclear TPI1/PKM2 increases H3K4 acetylation and activates the STAT3/P300 axis, resulting in SOX9 transcriptional activation and TMZ resistance in glioblastoma. ChIRP-MS and ChIRP-WB to identify Linc00942–TPI1/PKM2 interactions, Co-IP, nuclear fractionation, SOX9 knockdown rescue in vitro and in vivo Advanced science Medium 39342418
2024 The circular RNA circ-231 interacts with eIF4A3 and STAU1; this tripartite complex unwinds the secondary structure in the 5'UTR of TPI1 mRNA, enhancing its translation without altering mRNA transcript levels, thereby promoting ESCC cell migration and proliferation. ChIRP-MS, RNA immunoprecipitation, RNA pulldown, co-immunoprecipitation, EGFP reporter assay for 5'UTR unwinding, in vitro and in vivo proliferation/migration assays Journal of Cancer Medium 38577609
2026 NOP2 methyltransferase deposits m5C modification on TPI1 mRNA, stabilizing it and increasing TPI1 protein expression; NOP2 knockdown reduces m5C on TPI1 mRNA and decreases TPI1 stability, impairing glycolysis in larynx cancer cells. MeRIP (methylated RNA immunoprecipitation), RIP, dual-luciferase reporter assay, NOP2 knockdown/overexpression, glycolysis assays, xenograft models Molecular carcinogenesis Medium 41498196
2025 The R5G missense mutation in TPI1 produces a protein with essentially wild-type catalytic activity but markedly reduced steady-state protein levels due to increased instability of the mutant protein; compounds identified in a therapeutic screen significantly increased TPI1 protein levels and activity in patient cells with this allele, establishing protein stability as the primary pathogenic mechanism. Purification and biochemical characterization of recombinant TPIR5G, TPI activity assays, Western blot of patient fibroblasts, small-molecule treatment with TPI activity rescue assays Genes Medium 41153421
2025 TPI1 promotes M2-like macrophage polarization in THP-1 cells and contributes to resistance to KRAS inhibitors in KRAS-mutant lung adenocarcinoma cells, identifying a role in tumor immune remodeling beyond its glycolytic function. TPI1 overexpression/knockdown functional assays in THP-1 macrophages and LUAD epithelial cells, KRAS inhibitor sensitivity assays, pan-cancer transcriptomic/proteomic/scRNA-seq analysis Biochemical and biophysical research communications Low 41447883
2025 lncRNA HANR physically interacts with TPI1 protein, stabilizing it and promoting aerobic glycolysis and prostate cancer cell growth; silencing either HANR or TPI1 reduces glycolysis and tumor growth in vitro and in vivo. RNA immunoprecipitation, Co-IP, TPI1/HANR knockdown, glycolysis assays, in vivo xenograft models Experimental cell research Low 40921293
2025 Under hypoxia, TPI1 and HK2 protein levels increase in non-neuronal C6 glioma cells via IRES-mediated post-transcriptional regulation (not transcriptional upregulation); functional IRES elements were identified in the 5'UTR of TPI1 mRNA, with activity dependent on the polypyrimidine tract binding (PTB) protein. Di-cistronic and promoter-less di-cistronic reporter assays, MTT and LDH leakage assays under hypoxia, Western blot and qRT-PCR distinguishing protein from mRNA changes Artificial cells, nanomedicine, and biotechnology Medium 40105374
1979 TPI1 was regionally mapped to chromosome 12p (pter to p12) by karyological correlation analysis of human-Chinese hamster somatic cell hybrids with defined chromosome 12 deletions, establishing the chromosomal locus of the human TPI1 gene. Human-Chinese hamster somatic cell hybrid panel with X-ray/BrdU-induced chromosome breakage, isozyme marker analysis correlated to karyotype Cytogenetics and cell genetics High 477403

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Molecular cell 1260 16916647
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2011 Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 507 21565611
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2010 Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery. Journal of proteome research 422 20020773
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2016 Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics. Cell reports 306 27342126
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
2017 Optimized fragmentation schemes and data analysis strategies for proteome-wide cross-link identification. Nature communications 221 28524877
2012 Viral immune modulators perturb the human molecular network by common and unique strategies. Nature 219 22810585
2014 Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes. Journal of proteomics 215 25281560
2015 La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1). The Journal of biological chemistry 213 25940091
2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2020 Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nature cell biology 194 32203420
2004 Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins. The Journal of biological chemistry 185 15161933
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2012 Comprehensive analysis of host cellular interactions with human papillomavirus E6 proteins identifies new E6 binding partners and reflects viral diversity. Journal of virology 164 23015706
2020 Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Molecular cell 159 32416067
2009 Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6. Science signaling 159 20029029
2022 A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets. Nature biotechnology 140 36217030
2022 TPI1 activates the PI3K/AKT/mTOR signaling pathway to induce breast cancer progression by stabilizing CDCA5. Journal of translational medicine 51 35509067
2021 TPI1-reduced extracellular vesicles mediated by Rab20 downregulation promotes aerobic glycolysis to drive hepatocarcinogenesis. Journal of extracellular vesicles 44 34401050
2022 Elevated nuclear localization of glycolytic enzyme TPI1 promotes lung adenocarcinoma and enhances chemoresistance. Cell death & disease 41 35246510
1979 Regional assignment of human genes TPI1, GAPDH, LDHB, SHMT, and PEPB on chromosome 12. Cytogenetics and cell genetics 38 477403
2024 LDHA-induced histone lactylation mediates the development of osteoarthritis through regulating the transcription activity of TPI1 gene. Autoimmunity 34 39086231
2023 LKB1-Dependent Regulation of TPI1 Creates a Divergent Metabolic Liability between Human and Mouse Lung Adenocarcinoma. Cancer discovery 27 36715544
2024 Dopaminylation of endothelial TPI1 suppresses ferroptotic angiocrine signals to promote lung regeneration over fibrosis. Cell metabolism 25 39111287
2022 Daidzin inhibits hepatocellular carcinoma survival by interfering with the glycolytic/gluconeogenic pathway through downregulation of TPI1. BioFactors (Oxford, England) 23 35118741
2020 Proteomics analysis identified TPI1 as a novel biomarker for predicting recurrence of intrahepatic cholangiocarcinoma. Journal of gastroenterology 23 33089343
2008 Enhanced production of 1,2-propanediol by tpi1 deletion in Saccharomyces cerevisiae. Journal of microbiology and biotechnology 21 19047824
2022 Atractylenolide-1 affects glycolysis/gluconeogenesis by downregulating the expression of TPI1 and GPI to inhibit the proliferation and invasion of human triple-negative breast cancer cells. Phytotherapy research : PTR 19 36420870
2024 LncRNA-Mediated TPI1 and PKM2 Promote Self-Renewal and Chemoresistance in GBM. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 39342418
2019 Missense variant in TPI1 (Arg189Gln) causes neurologic deficits through structural changes in the triosephosphate isomerase catalytic site and reduced enzyme levels in vivo. Biochimica et biophysica acta. Molecular basis of disease 15 31075491
1993 Mapping of MYF5, C1R, MYHL, TPI1, IAPP, A2MR and RNR onto sheep chromosome 3q. Animal genetics 14 8273915
2023 TPI1 promotes MAPK/ERK-induced EMT, cell migration and invasion in lung adenocarcinoma. Thoracic cancer 13 38130074
2008 Sequencing and genotypic analysis of the triosephosphate isomerase (TPI1) locus in a large sample of long-lived Germans. BMC genetics 13 18510744
2022 miR-1285-3p targets TPI1 to regulate the glycolysis metabolism signaling pathway of Tibetan sheep Sertoli cells. PloS one 10 36137140
2024 Identification of TPI1 As a potential therapeutic target in pancreatic cancer with dependency of TP53 mutation using multi-omics analysis. Cancer science 8 39259678
2022 Systemic Analyses of the Expression of TPI1 and Its Associations with Tumor Microenvironment in Lung Adenocarcinoma and Squamous Cell Carcinoma. Disease markers 7 35126788
1991 Tpi-1 and Gapd are linked very closely on mouse chromosome 6. Genetical research 6 2040452
2025 TPI1 promotes p53 ubiquitination in bladder cancer by recruiting AKT to enhance MDM2 phosphorylation. Pharmacological research 4 40097123
2025 Inhibition of TPI1 Sensitizes Cisplatin-Resistant Oral Cancer to Ferroptosis. Biomedicines 4 40427052
2024 Single-Cell RNA Sequencing Revealed That the Enrichment of TPI1+ Malignant Hepatocytes Was Linked to HCC Metastasis and Immunosuppressive Microenvironment. Journal of hepatocellular carcinoma 4 38410699
2024 circular RNA circ-231 promotes protein biogenesis of TPI1 and PRDX6 through mediating the interaction of eIF4A3 with STAU1 to facilitate unwinding of secondary structure in 5' UTR, enhancing progression of human esophageal squamous cell carcinoma (ESCC). Journal of Cancer 2 38577609
1995 The gene for the peroxisomal targeting signal import receptor (PXR1) is located on human chromosome 12p13, flanked by TPI1 and D12S1089. Genomics 2 8586442
2025 IRES activation: HK2 and TPI1 glycolytic enzymes play a pivotal role in non-neuronal cell survival under hypoxia. Artificial cells, nanomedicine, and biotechnology 1 40105374
2025 LncRNA HANR promotes the aerobic glycolysis in prostate cancer by stabilizing TPI1. Experimental cell research 1 40921293
2025 TPI1 enhances gemcitabine resistance in bladder cancer by promoting autophagy through activating Beclin-1. Cell death & disease 1 41429797
2024 Ebselen and TPI-1, as RecG helicase inhibitors, potently enhance the susceptibility of Pseudomonas aeruginosa to DNA damage agents. Biochemical pharmacology 1 38354956
2026 NOP2 Promotes Glycolysis and Tumor Development in Larynx Cancer by Stabilizing TPI1 mRNA Through N5-Methylcytosine Modification. Molecular carcinogenesis 0 41498196
2026 TPI1 and TPM4 are strong candidate RNA biomarkers for systemic sclerosis. Arthritis research & therapy 0 41634796
2026 Familial Dystonia Due to Homozygous TPI1 c.718G>A (p.Glu240Lys): A Three-Sibling Case Series Including Two Treated with Deep Brain Stimulation of the Globus Pallidus Internus. Annals of Indian Academy of Neurology 0 41692693
2025 Propofol Inhibits Lung Cancer Glycolysis by Influencing the Deubiquitination Modification of TPI1 Regulated by USP5. Biochemical genetics 0 40956511
2025 Newly Identified TPI Deficiency Treatments Function for Novel Disease-Causing Allele, TPI1. Genes 0 41153421
2025 Increased Serum Levels of LDHA and TPI1 in Patients With Polycystic Ovary Syndrome. Proteomics. Clinical applications 0 41273239
2025 GRK4 R65L causes salt-sensitive hypertension by augmenting renal Hao2-mediated oxidative stress via increasing the phosphorylation of TPI1 and promoting H3K27ac expression. Free radical biology & medicine 0 41407053
2025 TPI1 promotes tumor progression and M2 macrophage polarization: Integrated pan-cancer and lung adenocarcinoma insights. Biochemical and biophysical research communications 0 41447883