Affinage

Showing DLAT — E2 is a alias.

DLAT

Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial · UniProt P10515

Length
647 aa
Mass
69.0 kDa
Annotated
2026-06-09
74 papers in source corpus 23 papers cited in narrative 23 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

DLAT (PDC-E2/dihydrolipoamide S-acetyltransferase) is the lipoylated E2 core subunit of the mitochondrial pyruvate dehydrogenase complex, and its activity is tuned by post-translational modification: KMT9 monomethylates DLAT at K596 to sustain PDC activity, de novo lipogenesis, and prostate cancer proliferation (PMID:39885202). Beyond catalysis, DLAT has emerged as a non-canonical acetyltransferase that directly acetylates substrate lysines to reprogram metabolism — it acetylates AUH at K109 to inhibit leucine catabolism and sustain mTOR activation in hepatocellular carcinoma (PMID:40112809), and acetylates the trifunctional protein subunit HADHA at K728 to inactivate fatty acid oxidation in HFpEF hearts (PMID:41826295); it also drives GLUT1 expression through H3K18 acetylation to promote glycolysis and EMT in HCC (PMID:39979835). DLAT is the key copper-binding lipoylated protein of cuproptosis: copper-driven oligomerization of lipo-DLAT executes copper ionophore–induced cell death, with the monomeric versus oligomeric balance determining cuproptosis susceptibility and drug resistance, and p32/C1QBP binding facilitating copper-induced oligomerization (PMID:38169635, PMID:37949877, PMID:37286711). Its abundance is controlled transcriptionally (Sp1), translationally (eIF4E), and through NAT10-mediated ac4C mRNA stabilization, with elesclomol-driven depletion of soluble DLAT feeding a NAT10 lactylation feedback loop (PMID:35869499, PMID:42085165). DLAT additionally localizes to the nucleus and to interaction partners that drive growth and metabolic signaling, including STAT5 co-activation (PMID:21397011), YAP1 dephosphorylation/activation (PMID:39460738), and a JAK2/STAT5/SREBP1 lipogenic axis (PMID:39871246), and engages thermogenic signaling by interacting with Trpv3 to activate a Ca2+–CaMKKβ–AMPK–UCP1 cascade in adipose browning (PMID:33657393, PMID:39631519). The lipoylated inner lipoyl domain of DLAT is the immunodominant autoantigen recognized by primary biliary cholangitis autoantibodies, where lipoylation and the surface-exposed lipoyl domain conformation determine epitope recognition (PMID:7694896, PMID:1701753).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1990 Medium

    Established that PBC autoantibody recognition of DLAT depends on the structure of its lipoyl domain rather than on the lysine sidechain chemistry alone, defining the molecular basis of the immunodominant autoepitope.

    Evidence Site-directed mutagenesis of the lipoyl-domain lysine with ELISA/immunoblot recognition by patient sera

    PMID:1701753

    Open questions at the time
    • Did not establish how lipoylation status alters the surface conformation recognized
    • Single-lab in vitro system
  2. 1993 Medium

    Showed that lipoylation of the inner lipoyl-domain lysine is required for high-affinity autoantibody recognition, linking the metabolic cofactor to autoimmune antigenicity in PBC.

    Evidence Comparison of recombinant lipoylated vs unlipoylated lipoyl domains by ELISA inhibition, immunoblot, and affinity measurement

    PMID:7694896

    Open questions at the time
    • Does not address why tolerance to this self-antigen is lost in disease
    • No structural model of the cofactor-peptide conformation
  3. 2011 Medium

    Revealed a non-mitochondrial role: nuclear DLAT acts as a STAT5 transcriptional co-activator, indicating functions beyond the PDC core.

    Evidence Subcellular fractionation, Co-IP with phospho-STAT5, confocal, and reporter/qRT-PCR in BaF3 cells

    PMID:21397011

    Open questions at the time
    • Mechanism of DLAT nuclear import not defined
    • Whether lipoyltransferase activity is required for co-activation unknown
  4. 2021 High

    Identified DLAT as the direct target of hyperforin and placed it upstream of AMPK/PGC-1α in adipose thermogenesis, the first functional link of DLAT to a thermogenic pathway.

    Evidence LiP-SMap, microscale thermophoresis, docking, plus Dlat ablation with thermogenesis readout in vitro and in vivo

    PMID:33657393

    Open questions at the time
    • Molecular effector downstream of DLAT not yet defined at this stage
    • Direct binding site of hyperforin not resolved
  5. 2022 Medium

    Defined how DLAT abundance is controlled, showing PM2.5 raises DLAT via Sp1 transcription and eIF4E translation, with elevated DLAT shifting NSCLC toward glycolysis.

    Evidence Polysome fractionation, ChIP, dual-luciferase reporter, Seahorse glycolysis assay with gain/loss-of-function

    PMID:35869499

    Open questions at the time
    • How elevated DLAT suppresses acetyl-CoA production mechanistically unclear
    • Single-lab cell-based system
  6. 2023 Medium

    Established DLAT as the executor of cuproptosis, where copper-ionophore-induced death requires DLAT and depends on its monomer/oligomer state and upstream PI3K/mTOR-driven expression.

    Evidence siRNA loss-of-function, copper chelation, monomer vs oligomer Western blots, pathway inhibition, and xenografts across HCC and prostate cancer

    PMID:37286711 PMID:37584654 PMID:37949877

    Open questions at the time
    • Structural basis of copper-induced lipo-DLAT oligomerization not resolved
    • Downstream death-execution steps after oligomerization undefined
  7. 2024 Medium

    Expanded DLAT interactomes linking it to thermogenesis, OXPHOS, and oncogenic signaling, including Trpv3-Ca2+-AMPK-UCP1, p32-facilitated copper oligomerization, and YAP1 activation.

    Evidence Co-IP/interaction assays, copper-binding and oligomerization assays, Seahorse, nuclear translocation, and rescue experiments across adipose, ccRCC, and TNBC models

    PMID:38169635 PMID:39460738 PMID:39631519

    Open questions at the time
    • Whether these interactions are mitochondrial vs cytosolic/nuclear not always resolved
    • Direct binding interfaces not mapped
  8. 2025 High

    Defined the non-canonical acetyltransferase function of DLAT — direct acetylation of AUH at K109 — and a KMT9-mediated K596 monomethylation that regulates PDC activity, plus H3K18ac-driven GLUT1 induction and JAK2/STAT5/SREBP1 lipogenic reprogramming.

    Evidence In vitro acetylation assays with site mutagenesis (AUH K109R), MS PTM mapping (K596me1), KMT9 depletion, chromatin acetylation analysis, and in vivo rescue/xenograft models

    PMID:39871246 PMID:39885202 PMID:39979835 PMID:40112809

    Open questions at the time
    • Catalytic mechanism of DLAT acting as a protein acetyltransferase not structurally defined
    • Full substrate repertoire and subcellular site of acetylation incompletely mapped
  9. 2026 Medium

    Showed DLAT-driven hyperacetylation inactivates fatty acid oxidation via HADHA-K728 acetylation, stabilizes mitochondrial GSH import through SLC25A39 binding, and is itself stabilized by NAT10-mediated ac4C in a cuproptosis feedback loop.

    Evidence In vitro acetylation with MS site identification, Co-IP/protein stability assays, ac4C modification and mRNA stability assays, with genetic perturbation and in vivo cardiac/CRC models

    PMID:41826295 PMID:42009144 PMID:42085165

    Open questions at the time
    • How DLAT switches between catalytic, acetyltransferase, and copper-binding roles is unresolved
    • Mechanism balancing pro-cuproptotic vs ferroptosis-protective functions undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The unifying biochemical basis by which a single mitochondrial PDC subunit performs metabolic catalysis, non-canonical protein/histone acetylation, copper-driven oligomerization, and nuclear transcriptional co-activation remains unresolved.
  • No structure explaining moonlighting acetyltransferase activity
  • Determinants of DLAT subcellular partitioning between mitochondria and nucleus unknown
  • How PTMs (K596me1, lipoylation) gate these distinct activities not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0140110 transcription regulator activity 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005739 mitochondrion 4 GO:0005634 nucleus 3
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 4
Partners
C1QBPCASP3CASP9SLC25A39STAT3STAT5TRPV3YAP1
Complex memberships
pyruvate dehydrogenase complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 Dlat (dihydrolipoamide S-acetyltransferase) was identified as a direct molecular target of the phytochemical hyperforin (HPF) using LiP-SMap (limited proteolysis-mass spectrometry), microscale thermophoresis, and molecular docking. Ablation of Dlat significantly attenuated HPF-mediated adipose tissue browning both in vitro and in vivo, placing Dlat upstream of AMPK and PGC-1α in a thermogenic pathway. LiP-SMap, microscale thermophoresis, molecular docking, Dlat knockout/ablation with thermogenesis phenotype readout Cell metabolism High 33657393
2024 Dlat interacts with transient receptor potential vanilloid 3 (Trpv3) to activate the calcium channel, increasing intracellular Ca2+ and activating CaMKKβ, which then stimulates AMPK to elevate Ucp1 expression and initiate adipose thermogenesis. HPF promotes thermogenesis by enhancing the Dlat-Trpv3 interaction independently of β3-adrenergic receptor signaling; thermogenic effects were reduced in Dlat+/- mice. Co-immunoprecipitation/interaction assays, Seahorse assays, JC-1 staining, qPCR, immunoblotting, Dlat heterozygous knockout mice on HFD Journal of advanced research Medium 39631519
2011 PDC-E2 (DLAT) is constitutively present in the nucleus of BaF3 cells and functions as a co-activator of STAT5-dependent gene transcription. Nuclear PDC-E2 is lipoylated and associates with PDC-E1; IL-3-induced phosphorylated STAT5 co-immunoprecipitates with nuclear PDC-E2. PDC-E2 overexpression augments STAT5-driven reporter activity and elevates endogenous SOCS3 mRNA levels. Subcellular fractionation, co-immunoprecipitation, confocal immunofluorescence, reporter assay, qRT-PCR Cellular signalling Medium 21397011
2025 DLAT directly acetylates AU RNA-binding methylglutaconyl-CoA hydratase (AUH) at lysine 109 (K109), inhibiting its activity and causing leucine accumulation that sustains mTOR complex activation in hepatocellular carcinoma. This reveals an unexpected acetyltransferase function of DLAT beyond its canonical role in the pyruvate dehydrogenase complex. Direct acetylation assay (in vitro), site-directed mutation of AUH K109, mass spectrometry identification of acetylation site, mTOR activity readout, xenograft models with AUHK109R-mRNA LNP rescue Cell metabolism High 40112809
2025 Mitochondrial lysine methyltransferase KMT9 monomethylates DLAT at lysine 596 (K596me1) to regulate pyruvate dehydrogenase complex (PDC) activity. KMT9 depletion compromises PDC activity, de novo lipogenesis, and prostate cancer cell proliferation in vitro and in a mouse model. KMT9 localizes to mitochondria specifically in prostate cancer cells. Mass spectrometry identification of K596me1, KMT9 depletion (in vitro and in vivo mouse model), PDC activity assay, de novo lipogenesis assay, mitochondrial fractionation/localization Nature communications High 39885202
2026 DLAT directly binds to the mitochondrial glutathione transporter SLC25A39 and enhances its protein stability independent of intracellular GSH levels, maintaining mitochondrial GSH import and redox homeostasis. Knockdown of DLAT or SLC25A39 disrupts mtGSH transport, elevates lipid peroxidation, and sensitizes colorectal cancer cells to ferroptosis. Co-immunoprecipitation (direct binding), siRNA knockdown with ferroptosis phenotype readout (lipid peroxidation, mtGSH measurement), protein stability assay Free radical biology & medicine Medium 42009144
2024 p32 (C1QBP) directly interacts with DLAT in the mitochondria, and increasing p32 expression increases oxidative phosphorylation by interacting with DLAT to regulate pyruvate dehydrogenase complex (PDHc) activation. p32 has direct binding affinity for copper and facilitates copper-induced oligomerization of lipoylated DLAT (lipo-DLAT) specifically in clear cell renal cell carcinoma (ccRCC) cells. Co-immunoprecipitation (p32-DLAT), copper binding assay, DLAT oligomerization assay, Seahorse assay (OXPHOS), animal models International journal of biological sciences Medium 38169635
2023 MELK activates PI3K/mTOR signaling to upregulate DLAT expression and stabilize mitochondrial function in hepatocellular carcinoma. Elevated DLAT (particularly the monomeric form) promotes elesclomol drug resistance and reduces cuproptosis susceptibility. Elesclomol treatment reduced TOM20 expression and increased DLAT oligomers, and MELK-mediated effects were abolished by elesclomol treatment. siRNA knockdown, DLAT overexpression, Western blotting (DLAT monomer vs. oligomer), PI3K/mTOR pathway inhibition, xenograft models Cell death & disease Medium 37949877
2023 DLAT functions as a cuproptosis promoter in hepatocellular carcinoma; siRNA-mediated downregulation of DLAT effectively inhibited copper ionophore (elesclomol)-induced cuproptosis in a copper-dependent manner. Selective Cu2+ chelation with ammonium tetrathiomolybdate also inhibited cuproptosis. siRNA loss-of-function, CCK8 cell viability assay, Western blotting (DLAT expression), elesclomol-copper cuproptosis induction Current medical science Medium 37286711
2023 Cuproptosis-upregulated DLAT inhibits autophagy, promotes G2/M phase cell cycle retention, and enhances docetaxel chemosensitivity in prostate cancer via the mTOR signaling pathway. These effects were demonstrated both in vitro and in xenograft models. Elesclomol-CuCl2 treatment, Western blotting, cell cycle flow cytometry, transmission electron microscopy, mTOR signaling analysis, xenograft model FASEB journal Medium 37584654
2022 PM2.5 upregulates DLAT expression through two mechanisms: (1) activating eIF4E to increase DLAT translation (shown by polysome fractionation), and (2) stimulating transcription factor Sp1 to augment DLAT promoter transcriptional activity (shown by ChIP and dual-luciferase reporter assay). Elevated DLAT promotes glycolysis but suppresses acetyl-CoA production, enhancing NSCLC malignancy. Polysome fractionation (Ribo-seq), ChIP, dual-luciferase reporter assay, Seahorse XF glycolysis stress assay, gain/loss-of-function experiments Journal of experimental & clinical cancer research Medium 35869499
2025 DLAT enhances glucose transporter 1 (GLUT1) expression via H3K18 acetylation, promoting aerobic glycolysis and epithelial-to-mesenchymal transition (EMT) to augment HCC metastasis. Functional cytology experiments confirmed that DLAT drives tumor metastasis by driving metabolic reprogramming. RNA sequencing, tissue microarrays, in vitro and in vivo functional assays, H3K18 acetylation analysis, Western blot Molecular medicine Medium 39979835
2021 PDC-E2 (DLAT) interacts with phosphorylated STAT3 (pY-STAT3) under cholestatic conditions in human cholangiocytes (NHC). GCDC treatment induced PDC-E2 expression and stimulated pY-STAT3 phosphorylation; siRNA silencing of PDC-E2 reduced pY-STAT3 expression specifically in NHC. Immunoprecipitation and proximity ligation assay confirmed GCDC-enhanced pY-STAT3 binding to PDC-E2 in nuclear and cytoplasmic fractions. PDC-E2/pS-STAT3 complexes were also detected in mitochondria. Co-immunoprecipitation, proximity ligation assay, siRNA knockdown, subcellular fractionation, MitoTracker co-localization Scientific reports Medium 34737337
2024 DLAT directly interacts with YAP1, leading to dephosphorylation and activation of YAP1 and increased nuclear translocation, thereby transcriptionally activating downstream oncogenes and promoting the malignant phenotype of triple-negative breast cancer. Rescue experiments confirmed that DLAT promotes malignant behavior through a YAP1-dependent pathway. Co-immunoprecipitation, cytoplasmic-nuclear separation experiments, Western blot, rescue experiments with YAP1 manipulation Cancer biology & therapy Medium 39460738
2025 DLAT directly binds to CASP3 and CASP9 proteins in granulosa cells to inhibit apoptosis, and DLAT overexpression increased PCNA and MCL1 levels to promote granulosa cell proliferation. Pyruvate upregulates DLAT expression, and high DLAT levels in large follicles promote follicular growth. Protein binding assay (DLAT-CASP3/CASP9), qRT-PCR, Western blot, cell proliferation assay, in vivo follicular growth experiments Cells Low 40136693
2026 Dlat acts as a key transacetylase for mitochondrial protein hyperacetylation in HFpEF hearts. Dlat directly acetylates the alpha subunit of mitochondrial trifunctional protein (HADHA) at K728, inactivating HADHA enzymatic activity and inhibiting fatty acid oxidation. Dlat overexpression enhanced FAO-related protein acetylation and exacerbated cardiac lipid metabolism disturbances; Dlat knockdown mitigated FAO inhibition and HFpEF phenotypes. In vitro acetylation assay (Dlat→HADHA K728), site-specific acetylation identification by MS, Dlat KO/OE with FAO and cardiac function readouts Nature communications High 41826295
2025 DLAT promotes lipid metabolism reprogramming in ovarian cancer via the JAK2/STAT5/SREBP1 signaling axis. DLAT silencing reduced lipid content and impaired OC cell proliferation, migration, and invasion. DLAT upregulated SREBP1 expression through JAK2/STAT5 signaling, enhancing fatty acid synthesis; SREBP1 was essential for DLAT-dependent OC cell growth and metastasis in vitro and in vivo. siRNA knockdown, Western blot (JAK2/STAT5/SREBP1 pathway), lipid detection assays, SREBP1 overexpression rescue, xenograft mouse model Cancer cell international Medium 39871246
2024 Microglial exosomes facilitate transfer of PKM2 to neurons, leading to upregulation of DLAT expression and increased copper-induced neuronal death in Alzheimer's disease context. Inhibition of PKM2 transfer via exosomes resulted in significant reduction in DLAT expression, mitigating neuronal death. DLAT was validated as increased in 5xFAD transgenic mice hippocampus. In vitro exosome transfer assay, PKM2 inhibition, siRNA/knockdown of PKM2 transfer, 5xFAD transgenic mouse model, Western blot CNS neuroscience & therapeutics Low 39428563
1993 Lipoylation of the lysine residue in the inner lipoyl domain of human PDC-E2 is crucial for effective autoantibody recognition in primary biliary cirrhosis. Purified lipoylated and unlipoylated forms of the inner lipoyl domain were compared in immunoblotting, ELISA inhibition experiments, and antibody affinity measurements; PBC autoantibodies have higher relative affinity for the lipoylated form, recognizing a unique peptide-cofactor conformation. Recombinant protein expression in E. coli, affinity purification of lipoylated/unlipoylated forms, ELISA inhibition, immunoblotting, affinity measurements Hepatology Medium 7694896
1990 Site-directed mutagenesis of the lysine residue in the lipoyl domain of human PDC-E2 (replacing lysine with glutamine, histidine, or tyrosine) demonstrated that the recognition of the immunodominant autoepitope by PBC patient sera is dependent on the lipoyl domain structure rather than simply the charge or chemistry of the lysine sidechain alone; the recognition reflects the surface-exposed, hydrophilic, mobile nature of the lipoyl domain region. Oligonucleotide-directed site-directed mutagenesis, ELISA, immunoblotting, specific absorption assays with patient sera Hepatology Medium 1701753
2015 siRNA-mediated knockdown of DLAT in gastric cancer cell lines supported a role for DLAT in cell proliferation and carbohydrate metabolism, consistent with its function as a subunit of the pyruvate dehydrogenase complex involved in metabolic reprogramming in cancer. siRNA knockdown, cell proliferation assay, metabolic assays American journal of translational research Low 26279757
1993 PDC-E2 (DLAT) gene was mapped to human chromosome 11 band q23.1 using fluorescence in situ hybridization, and a TaqI restriction fragment length polymorphism was identified. The chromosomal location was experimentally determined. Fluorescence in situ hybridization (FISH), RFLP analysis with restriction enzymes Autoimmunity Medium 8102256
2026 NAT10 enhances DLAT mRNA stability by mediating its N4-acetylcytidine (ac4C) modification, promoting DLAT expression and cuproptosis in colorectal cancer. Lactylation of NAT10 at K426 enhances NAT10 catalytic activity, while SIRT1-mediated delactylation of NAT10-K426 inhibits cuproptosis. Elesclomol-induced reduction of soluble DLAT feeds back to enhance NAT10-K426 lactylation, creating a positive feedback loop. ac4C RNA modification assay, NAT10 knockdown/overexpression, SIRT1 inhibition (selisistat), DLAT mRNA stability assay, lactylation site identification (K426) Proceedings of the National Academy of Sciences Medium 42085165

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity. Cell metabolism 166 33657393
2008 Crystal structure of DltA. Implications for the reaction mechanism of non-ribosomal peptide synthetase adenylation domains. The Journal of biological chemistry 111 18784082
2000 Mimicry peptides of human PDC-E2 163-176 peptide, the immunodominant T-cell epitope of primary biliary cirrhosis. Hepatology (Baltimore, Md.) 103 10827144
2023 MELK promotes HCC carcinogenesis through modulating cuproptosis-related gene DLAT-mediated mitochondrial function. Cell death & disease 93 37949877
2022 PM2.5 promotes NSCLC carcinogenesis through translationally and transcriptionally activating DLAT-mediated glycolysis reprograming. Journal of experimental & clinical cancer research : CR 87 35869499
2015 DLAT subunit of the pyruvate dehydrogenase complex is upregulated in gastric cancer-implications in cancer therapy. American journal of translational research 84 26279757
2023 Cuproptosis enhances docetaxel chemosensitivity by inhibiting autophagy via the DLAT/mTOR pathway in prostate cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 70 37584654
2008 CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis. Journal of autoimmunity 69 18644699
1995 Immunohistochemical analysis of adhesion molecules in the micro-environment of portal tracts in relation to aberrant expression of PDC-E2 and HLA-DR on the bile ducts in primary biliary cirrhosis. The Journal of pathology 65 7538164
2008 Crystal structure and enantiomer selection by D-alanyl carrier protein ligase DltA from Bacillus cereus. Biochemistry 60 18847223
1995 Abnormal expression of PDC-E2 on the apical surface of biliary epithelial cells in patients with antimitochondrial antibody-negative primary biliary cirrhosis. Hepatology (Baltimore, Md.) 60 7590661
1993 Lipoylated and unlipoylated domains of human PDC-E2 as autoantigens in primary biliary cirrhosis: significance of lipoate attachment. Hepatology (Baltimore, Md.) 60 7694896
2013 dltA overexpression: A strain-independent keystone of daptomycin resistance in methicillin-resistant Staphylococcus aureus. International journal of antimicrobial agents 53 24183798
2011 Nuclear localization of pyruvate dehydrogenase complex-E2 (PDC-E2), a mitochondrial enzyme, and its role in signal transducer and activator of transcription 5 (STAT5)-dependent gene transcription. Cellular signalling 51 21397011
1990 Site-directed mutagenesis of lysine within the immunodominant autoepitope of PDC-E2. Hepatology (Baltimore, Md.) 50 1701753
2000 Fine specificity of T cells reactive to human PDC-E2 163-176 peptide, the immunodominant autoantigen in primary biliary cirrhosis: implications for molecular mimicry and cross-recognition among mitochondrial autoantigens. Hepatology (Baltimore, Md.) 49 11050037
2009 Crystal structure of Bacillus cereus D-alanyl carrier protein ligase (DltA) in complex with ATP. Journal of molecular biology 45 19324056
2002 Comprehensive mapping of HLA-A0201-restricted CD8 T-cell epitopes on PDC-E2 in primary biliary cirrhosis. Hepatology (Baltimore, Md.) 44 12395322
2002 Characterization of recombinant monoclonal IgA anti-PDC-E2 autoantibodies derived from patients with PBC. Hepatology (Baltimore, Md.) 44 12447863
2004 Sidechain biology and the immunogenicity of PDC-E2, the major autoantigen of primary biliary cirrhosis. Hepatology (Baltimore, Md.) 36 15558739
2009 Inactivation of DltA modulates virulence factor expression in Streptococcus pyogenes. PloS one 35 19401780
1994 Heterogeneity of combinatorial human autoantibodies against PDC-E2 and biliary epithelial cells in patients with primary biliary cirrhosis. Hepatology (Baltimore, Md.) 34 7521314
2011 Electrophile-modified lipoic derivatives of PDC-E2 elicits anti-mitochondrial antibody reactivity. Journal of autoimmunity 33 21763105
1994 Nucleotide sequence analysis of natural and combinatorial anti-PDC-E2 antibodies in patients with primary biliary cirrhosis. Recapitulating immune selection with molecular biology. Journal of immunology (Baltimore, Md. : 1950) 33 8133065
2023 DLAT as a Cuproptosis Promoter and a Molecular Target of Elesclomol in Hepatocellular Carcinoma. Current medical science 30 37286711
2025 Pyruvate metabolism enzyme DLAT promotes tumorigenesis by suppressing leucine catabolism. Cell metabolism 29 40112809
2016 Betulin inhibits virulence and biofilm of Streptococcus pyogenes by suppressing ropB core regulon, sagA and dltA. Pathogens and disease 28 27596811
1997 Analysis of T-cell receptor beta of the T-cell clones reactive to the human PDC-E2 163-176 peptide in the context of HLA-DR53 in patients with primary biliary cirrhosis. Hepatology (Baltimore, Md.) 27 9303504
2024 p32 regulates glycometabolism and TCA cycle to inhibit ccRCC progression via copper-induced DLAT lipoylation oligomerization. International journal of biological sciences 25 38169635
2004 A novel lectin, DltA, is required for expression of a full serum resistance phenotype in Haemophilus ducreyi. Infection and immunity 22 15155648
1999 In situ nucleic acid detection of PDC-E2, BCOADC-E2, OGDC-E2, PDC-E1alpha, BCOADC-E1alpha, OGDC-E1, and the E3 binding protein (protein X) in primary biliary cirrhosis. Hepatology (Baltimore, Md.) 22 10385636
2025 DLAT activates EMT to promote HCC metastasis by regulating GLUT1-mediated aerobic glycolysis. Molecular medicine (Cambridge, Mass.) 18 39979835
1996 Random phage mimotopes recognized by monoclonal antibodies against the pyruvate dehydrogenase complex-E2 (PDC-E2). Proceedings of the National Academy of Sciences of the United States of America 18 8855289
1992 Characterization and epitope mapping of human monoclonal antibodies to PDC-E2, the immunodominant autoantigen of primary biliary cirrhosis. Journal of autoimmunity 17 1283300
2010 Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis. World journal of gastroenterology 16 20180236
1998 Immunogenetic analysis of a panel of monoclonal IgG and IgM anti-PDC-E2/X antibodies derived from patients with primary biliary cirrhosis. Journal of hepatology 12 9566826
2025 A metallic metabolic nano-regulator reprograms the PKM2/HIF-1α/DLAT axis to amplify tumor-specific cuproptosis. Biomaterials 11 40815897
2022 DltC acts as an interaction hub for AcpS, DltA and DltB in the teichoic acid D-alanylation pathway of Lactiplantibacillus plantarum. Scientific reports 11 35907949
2014 Thiolation-enhanced substrate recognition by D-alanyl carrier protein ligase DltA from Bacillus cereus. F1000Research 11 25285205
2022 Structural and functional analysis of the D-alanyl carrier protein ligase DltA from Staphylococcus aureus Mu50. Acta crystallographica. Section D, Structural biology 10 35362466
2006 Differential epitope mapping of antibodies to PDC-E2 in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation and primary biliary cirrhosis. Blood 9 17068145
1999 Anti-idiotypic antibodies to anti-PDC-E2 in primary biliary cirrhosis and normal subjects. Hepatology (Baltimore, Md.) 9 10051459
2024 Novel Insights Into DLAT's Role in Alzheimer's Disease-Related Copper Toxicity Through Microglial Exosome Dynamics. CNS neuroscience & therapeutics 8 39428563
2025 DLAT is involved in ovarian cancer progression by modulating lipid metabolism through the JAK2/STAT5A/SREBP1 signaling pathway. Cancer cell international 7 39871246
2018 The regulation of DLTA gene in bacterial growth and biofilm formation by Parvimonas micra. European review for medical and pharmacological sciences 7 30024592
2009 dltA gene mutation in the teichoic acids alanylation system of Lactococcus garvieae results in diminished proliferation in its natural host. Veterinary microbiology 7 20042300
2025 Mitochondrial KMT9 methylates DLAT to control pyruvate dehydrogenase activity and prostate cancer growth. Nature communications 6 39885202
2024 Identification of a novel PDC-E2 epitope in primary biliary cholangitis: Application for engineered Treg therapy. Journal of autoimmunity 6 39476446
2023 Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model. Investigative and clinical urology 5 37341010
1993 Chromosome localization and RFLP analysis of PDC-E2: the major autoantigen of primary biliary cirrhosis. Autoimmunity 4 8102256
2025 Copper ionophore enhanced cisplatin efficiency through DLAT-cuprotosis. Toxicology and applied pharmacology 3 40749953
2024 Targeting Dlat-Trpv3 pathway by hyperforin elicits non-canonical promotion of adipose thermogenesis as an effective anti-obesity strategy. Journal of advanced research 3 39631519
2021 p-STAT3 is a PDC-E2 interacting partner in human cholangiocytes and hepatocytes with potential pathobiological implications. Scientific reports 3 34737337
1993 Antibody to two forms of dihydrolipoamide acetyltransferase (PDC-E2) in primary biliary cirrhosis. Liver 3 8336525
2025 Modulation of Cuproptosis Pathway Genes (DLAT, FDX1) and Antioxidant Enzyme Activities in Obese Mice in Response to Quercetin and Calorie Restriction. DNA and cell biology 2 40354319
2025 [Acupuncture inhibits cuproptosis to prolong the time window of thrombolysis by down-regulating cerebral FDX1 and DLAT in rats with cerebral infarction]. Zhen ci yan jiu = Acupuncture research 2 40691025
2025 Mitochondrial uncoupling sensitizes gastric cancer cells to elesclomol-induced cuproptosis via FDX1/DLAT upregulation. Free radical biology & medicine 2 41407052
2024 DLAT promotes triple-negative breast cancer progression via YAP1 activation. Cancer biology & therapy 2 39460738
2025 Pyruvate Regulates the Expression of DLAT to Promote Follicular Growth. Cells 1 40136693
2025 Role of DLAT in cuproptosis and autophagy in hippocampal tissue of PTSD rats with high-voltage electrical burns. Burns : journal of the International Society for Burn Injuries 1 40319822
2025 Synthesis of New DltA Inhibitors and Their Application as Adjuvant Antibiotics to Re-Sensitize Methicillin-Resistant Staphylococcus aureus. Molecules (Basel, Switzerland) 1 40572534
2025 Role of DLAT-Mediated Neuron Cuproptosis in Cognitive Impairment Induced by Lead Exposure. Journal of applied toxicology : JAT 1 40891127
2024 Serum DLAT Is a Potential Diagnostic Marker in AFP-Negative HCC. Biological & pharmaceutical bulletin 1 39710381
2026 Plasma anti-DLAT autoantibody as a novel diagnostic biomarker in breast cancer. Clinical immunology (Orlando, Fla.) 0 41643757
2026 Triptolide from Tripterygium wilfordii Suppresses Glycolysis and Induces Cuproptosis via the HK2/DLAT Signaling Pathway in Colorectal Cancer. The American journal of Chinese medicine 0 41709570
2026 Sanguinarine exerts anti-hepatocellular carcinoma activity by targeting FDX1 to induce FDX1/LIAS/DLAT/HSP70 axis-dependent cuproptosis. Acta biochimica et biophysica Sinica 0 41764347
2026 Pyruvate metabolism enzyme Dlat induces mitochondria protein hyperacetylation to limit fatty acid oxidation in the HFpEF heart. Nature communications 0 41826295
2026 DLAT inhibits ferroptosis to promote malignant progression of gastric cancer through Nrf2/HO-1/GPX4 signaling pathway. Biology direct 0 41928317
2026 DLAT sustains redox homeostasis and prevent colorectal cancer from ferroptosis by regulating SLC25A39-mediated mitochondrial glutathione transport. Free radical biology & medicine 0 42009144
2026 Lactylated NAT10 contributes to elesclomol-triggered cuproptosis via the NAT10/ac4C-DLAT-mRNA/DLAT positive feedback loop in CRC. Proceedings of the National Academy of Sciences of the United States of America 0 42085165
2026 MELK inhibits cuproptosis in diffuse large B-cell lymphoma cells via the PI3K/mTOR/S6K-DLAT signaling axis. Molecular and cellular biochemistry 0 42228272
2026 Native mass spectrometry reveals DltA catalysis, DltC loading, and inhibition in the d-alanylation pathway. RSC advances 0 42245989
2024 Carbamazepine responsive episodic dystonia and hallucination due to pyruvate dehydrogenase E2 (DLAT) gene mutation. Journal of neurogenetics 0 39007626
2004 [Prediction and identification of autoepitopes of PDC-E2 specific CD8+ CTL in primary biliary cirrhosis patients]. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 0 15562760

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