Affinage

PPARD

Peroxisome proliferator-activated receptor delta · UniProt Q03181

Length
441 aa
Mass
49.9 kDa
Annotated
2026-06-10
92 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPARD (PPARβ/δ) is a ligand-activated nuclear receptor that cooperatively binds PPAR-responsive elements with RXRα and acts as a context-dependent transcriptional activator or repressor, originally characterized as a repressor of PPARα and thyroid hormone receptor activation that titrates a factor required for their activity (PMID:7876127). Its activity is gated at the protein level: a G32E substitution in the A/B domain reduces ligand-dependent transcription by promoting CRM1-mediated nuclear export and reducing A/B-domain ubiquitination without affecting ligand binding (PMID:24058710), and its expression is shaped by cis-regulatory architecture, including an intron-2 insulator/silencer module and TCF7L2-responsive promoter elements (PMID:26599230, PMID:29583017). As a transcription factor, PPARD directly binds target gene promoters identified by ChIP-seq, including PPARG (PMID:28539839), and represses CDC20 and MECP2 (PMID:40031093, PMID:40538591). A dominant theme in the corpus is PPARD's role in carcinogenesis and tissue remodeling: it drives colorectal tumorigenesis by augmenting β-catenin activation through BMP7/TAK1 signaling (PMID:30679176), promotes metastasis via IL-8–driven angiogenesis and epithelial–mesenchymal transition (PMID:28097239), and induces invasive gastric adenocarcinoma through CCL20/CXCL1 chemokine induction and a self-sustaining PPARD/IFNγ feedback loop (PMID:30885780). PPARD also senses dietary fatty acids to control immune and stromal cell states, mediating dendritic cell activation in atherosclerosis (PMID:31919912), restraining macrophage IL-23 via a PPARδ/BCL6 repressor complex downstream of CD36 lipid uptake (PMID:40717126), and driving smooth muscle cell dedifferentiation through a PDK4/ANGPTL4 axis (PMID:40652248). It additionally regulates Sertoli cell proliferation and spermatogenesis through temporal control of ERK signaling (PMID:26242735).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1995 Medium

    Established the founding biochemical identity of PPARD as an RXRα-partnered nuclear receptor that can repress rather than activate transcription, distinguishing it from PPARα.

    Evidence Transient transfection reporter, cooperative DNA-binding, and ligand-binding assays in the presence of hRXRα

    PMID:7876127

    Open questions at the time
    • The titrated 'factor' required for activation was not identified
    • Endogenous target genes not defined
  2. 2007 Medium

    Demonstrated PPARD activity is pharmacologically tractable by identifying the first selective small-molecule antagonist, enabling loss-of-function dissection.

    Evidence Cellular and biochemical characterization of an antagonist ligand

    PMID:17975020

    Open questions at the time
    • In vivo efficacy and selectivity not established in this work
    • Target gene consequences of antagonism not mapped
  3. 2011 Medium

    Linked a specific PPARD coding variant to a phenotype, showing the G32E A/B-domain mutation causally drives β-catenin target downregulation in tissue patterning.

    Evidence QTL mapping, IBD/selective sweep analysis, and luciferase reporter assays in porcine populations

    PMID:21573137

    Open questions at the time
    • Molecular mechanism of the A/B-domain effect not resolved here
    • Restricted to porcine ear-size QTL
  4. 2013 High

    Resolved the molecular mechanism of the G32E variant, showing it impairs transcription by promoting CRM1-mediated nuclear export and reducing ubiquitination rather than altering ligand affinity.

    Evidence Reporter assays, live-cell localization, co-IP for ubiquitination, and SPR for ligand binding

    PMID:24058710

    Open questions at the time
    • E3 ligase and CRM1-binding determinants not identified
    • Connection to physiological regulation of wild-type PPARD unclear
  5. 2015 High

    Defined a developmental role in male reproduction, showing PPARD controls Sertoli cell proliferation and tight-junction formation through temporal ERK inhibition.

    Evidence Ppard knockout mouse phenotyping plus TM4 Sertoli cell ligand/inverse-agonist treatment and ERK pathway readouts

    PMID:26242735

    Open questions at the time
    • Direct transcriptional targets linking PPARD to ERK not identified
    • Ligand identity in vivo unknown
  6. 2015 Medium

    Mapped upstream transcriptional control of PPARD, showing TCF7L2 binds the promoter and functional 5' SNPs modulate its expression.

    Evidence Reporter assays, EMSA, western blot, and population association in pig models

    PMID:26599230

    Open questions at the time
    • TCF7L2 regulation not confirmed in human cells
    • Crosstalk with Wnt signaling at PPARD promoter unexplored
  7. 2017 High

    Established PPARD as a driver of metastasis, showing it is required for EMT, migration, invasion, and IL-8–driven angiogenesis.

    Evidence CRISPR deletion in cancer cells, in vivo metastasis models, transcriptome profiling, and angiogenesis assays

    PMID:28097239

    Open questions at the time
    • Direct vs indirect regulation of target genes (GJA1, VIM, SPARC) not distinguished
    • Ligand driving metastatic activity not defined
  8. 2017 High

    Identified direct genomic targets of PPARD including PPARG by ChIP-seq, linking the G32E variant to cartilage developmental phenotypes.

    Evidence ChIP-seq, apoptosis and differentiation assays, and wild-type vs G32E comparison in cartilage progenitors

    PMID:28539839

    Open questions at the time
    • Whether PPARG activation is the sole effector unclear
    • Generalizability beyond auricular cartilage untested
  9. 2018 Medium

    Characterized the cis-regulatory architecture of the human PPARD locus, identifying an intron-2 CTCF insulator and an interacting silencer element.

    Evidence Bioinformatic prediction, reporter assays, CTCF binding assay, and ENCODE 5C data

    PMID:29583017

    Open questions at the time
    • Physiological contexts engaging these elements not defined
    • Effect on endogenous PPARD expression not measured
  10. 2019 High

    Placed PPARD upstream of β-catenin in colorectal tumorigenesis via BMP7/TAK1 signaling, with bidirectional genetic and pharmacological control of tumor outcome.

    Evidence PPARD gain/loss mouse models with Apc mutation, human CRC organoids, agonist/antagonist treatment, and reverse-phase protein microarray

    PMID:30679176

    Open questions at the time
    • Direct transcriptional targets within the BMP7/TAK1 axis not pinpointed
    • Mechanism of additional proinvasive pathways (PDGFRβ, AKT1) not detailed
  11. 2019 High

    Demonstrated PPARD drives gastric carcinogenesis through chemokine-mediated inflammation and a self-amplifying PPARD/IFNγ feedback loop.

    Evidence Villin-PPARD transgenic mice, lineage tracing, cytokine profiling, and transcriptome analysis

    PMID:30885780

    Open questions at the time
    • Whether CCL20/CXCL1 are direct PPARD targets not shown
    • Molecular basis of the IFNγ feedback link unresolved
  12. 2020 High

    Showed PPARD acts as a fatty-acid sensor in dendritic cells, mediating palmitic acid–induced activation and Th1 polarization in atherosclerosis.

    Evidence CD11c-conditional Ppard knockout in ApoE-/- mice plus bone marrow-derived DC culture with palmitic acid

    PMID:31919912

    Open questions at the time
    • Transcriptional targets controlling co-stimulatory molecule expression not identified
    • Direct fatty-acid binding to PPARD in DCs not demonstrated
  13. 2025 High

    Defined a PPARδ/BCL6 repressor mechanism by which dietary lipid uptake through CD36 suppresses macrophage IL-23, linking lipid sensing to intestinal immune tolerance.

    Evidence Macrophage CD36 conditional knockout, DSS colitis model, oleic acid/LPS treatment, and PPARδ/BCL6 complex characterization

    PMID:40717126

    Open questions at the time
    • Direct binding stoichiometry of the PPARδ/BCL6 complex at Il23a not fully resolved
    • Generalizability to human macrophages untested
  14. 2025 Medium

    Identified PPARD as both a target and effector of metabolic epigenetic signaling, induced by H3K18 lactylation and driving AKT-dependent survival under glycolytic conditions.

    Evidence H3K18la ChIP-seq, multi-omics, ATAC-seq, and HDAC2/3 eraser identification in breast cancer cells

    PMID:39922804

    Open questions at the time
    • HDAC2/3 eraser activity at the PPARD locus not reconstituted
    • Direct vs indirect AKT regulation by PPARD unresolved
  15. 2025 Medium

    Placed PPARD upstream of MECP2/STAT3 in immune balance, showing it represses MECP2 to alleviate Th17/Treg imbalance.

    Evidence PPARD siRNA knockdown with MECP2 deletion and STAT3 inhibition epistasis in a rat CARAS model

    PMID:40031093

    Open questions at the time
    • Direct binding of PPARD to the MECP2 promoter not demonstrated
    • Single model system
  16. 2025 High

    Linked PPARD to smooth muscle phenotypic switching, showing it activates a PDK4/ANGPTL4 axis driving SMC dedifferentiation under lipid excess.

    Evidence High-fat diet mice, lipid-treated human gastric SMCs with siRNA knockdown and PPARD activation, lipidomics/RNA-seq, validated in human tissue

    PMID:40652248

    Open questions at the time
    • Whether PDK4/ANGPTL4 are direct transcriptional targets not established
    • Reversibility of the dedifferentiated phenotype untested
  17. 2025 Medium

    Showed ACSS2-driven H3K27 acetylation at the PPARD promoter elevates PPARD, which transcriptionally activates BCAT1 to reprogram BCAA catabolism in pancreatic cancer.

    Evidence ACSS2 knockout, ChIP for H3K27ac at the PPARD promoter, and functional proliferation/invasion assays

    PMID:40908872

    Open questions at the time
    • Direct PPARD binding at the BCAT1 promoter not confirmed
    • Single lab; mechanistic generality unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous physiological ligands engaging PPARD across its diverse contexts and the rules governing its switch between activator and repressor modes remain undefined.
  • No structural model of context-dependent activator/repressor switching
  • Direct genome-wide target set unifying cancer, immune, and developmental roles not consolidated
  • Cofactor exchange mechanisms underlying repression not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 3 GO:0008289 lipid binding 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 6 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
BCL6CRM1RXRATCF7L2
Complex memberships
PPARD/RXRα heterodimerPPARδ/BCL6 repressor complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 hNUC1 (PPARD) acts as a repressor of hPPARα and human thyroid hormone receptor transcriptional activation. It cooperatively binds a PPAR-responsive element with hRXRα, and in the presence of hRXRα its affinity for the peroxisome proliferator ligand is comparable to hPPARα. Repression of hPPARα can be overcome by transfecting excess hPPARα, suggesting hNUC1 titrates out a factor required for activation. Transient transfection reporter assays, cooperative DNA binding assays, ligand binding assays in the presence of hRXRα The Journal of biological chemistry Medium 7876127
2007 A selective small-molecule PPARβ/δ (PPARD) antagonist ligand was identified and characterized, demonstrating that the receptor's biological activity can be blocked by a specific ligand — the first antagonist described for this receptor subtype. Cellular and biochemical characterization of small molecule antagonist ligand binding and functional activity Molecular endocrinology (Baltimore, Md.) Medium 17975020
2011 A missense mutation (G32E) in the A/B domain of porcine PPARD is the causal variant underlying a major QTL for ear size; the mutation mediates downregulation of β-catenin and its target gene expression crucial for fat deposition in skin. QTL mapping, identical-by-descent analysis, selective sweep analysis, luciferase reporter assays for β-catenin target gene expression, association studies in experimental cross and outbred populations PLoS genetics Medium 21573137
2013 The G32E substitution in porcine PPARD (A/B domain) reduces transcription activity in a ligand-dependent manner, promotes CRM1-mediated nuclear export of PPARD, and greatly reduces ubiquitination of the A/B domain, consequently decreasing transcriptional activity. Surface plasmon resonance showed the mutation has negligible effect on ligand binding affinity. Luciferase reporter assays, subcellular localization imaging in PK-15 cells and primary chondrocytes, co-immunoprecipitation for ubiquitination, surface plasmon resonance for ligand binding PloS one High 24058710
2015 PPARD modulates spermatogenesis by regulating Sertoli cell function via temporal inhibition of ERK activation. Ligand activation of PPARD inhibited Sertoli cell (TM4) proliferation; PPARD-dependent ERK signaling altered expression of claudin-11, p27, cyclin D1, and cyclin D2, causing inhibition of proliferation, maturation, and tight junction formation in Sertoli cells. Ppard knockout mouse phenotyping, immunofluorescence, western blotting, Sertoli cell line (TM4) treatment with PPARD ligand and inverse agonist (DG172), ERK pathway analysis The Journal of biological chemistry High 26242735
2015 In porcine PPARD, functional SNPs (g.1015 A>G and g.1018 T>C) in the 5' regulatory region affect transcriptional activity; TCF7L2 (transcription factor 7-like 2) enhances PPARD promoter transcription in C2C12 and 3T3-L1 cells and binds differentially to the haplotypes, with haplotype AC showing the lowest TCF7L2 binding capacity and transcriptional activity. Luciferase reporter assays, electrophoretic mobility shift assay (nuclear extract binding), western blot of PPARD protein expression, qPCR, association analysis in pig populations PloS one Medium 26599230
2017 PPARD promotes tumor metastasis by promoting angiogenesis via interleukin-8 (IL-8) in vivo and in vitro. Genetic deletion of PPARD in cancer cells identified pro-metastatic target genes (GJA1, VIM, SPARC, STC1, SNCG) and demonstrated PPARD's necessity for epithelial-mesenchymal transition, migration, and invasion. Genetic deletion (CRISPR) of PPARD in cancer cells, in vivo metastasis models, transcriptome profiling, TCGA database analysis, migration/invasion assays, angiogenesis assay with IL-8 quantification JCI insight High 28097239
2017 PPARD retards auricular cartilage development by accelerating apoptosis of cartilage stem/progenitor cells (CSPCs), promoting terminal differentiation, and degrading cartilage extracellular matrix. ChIP-seq identified direct PPARD target genes including PPARG, and the G32E mutant upregulates PPARG expression, leading to downregulation of genes that inhibit cartilage growth. ChIP-seq, gene expression analysis, apoptosis assays, histological analysis of cartilage, comparison of wild-type vs. G32E mutant PPARD International journal of biological sciences High 28539839
2018 An insulator element (CTCF binding confirmed) and a repressor/silencer element were identified and functionally validated in intron 2 of the human PPARD gene; the two cis-regulatory elements interact with each other. Bioinformatic prediction, transient transfection reporter assays, CTCF binding assay, ENCODE 5C data Epigenomics Medium 29583017
2019 PPARD overexpression or deletion in intestinal epithelial cells augments or suppresses β-catenin activation via up- or downregulation of BMP7/TAK1 signaling, strongly promoting or suppressing colorectal cancer. Depletion of PPARD in human colorectal cancer organoid cells inhibited BMP7/β-catenin signaling and suppressed organoid self-renewal. PPARD agonist GW501516 enhanced tumorigenesis in Apc mice while antagonist GSK3787 suppressed it. Reverse-phase protein microarray identified additional PPARD-regulated proinvasive pathways: connexin 43, PDGFRβ, AKT1, EIF4G1, and CDK1. Mouse models of PPARD overexpression/deletion combined with Apc mutation, human CRC organoids with PPARD depletion, pharmacological agonist/antagonist treatment in Apc mice, reverse-phase protein microarray Cancer research High 30679176
2019 PPARD overexpression in villin-positive gastric progenitor cells (VGPCs) causes spontaneous invasive gastric adenocarcinoma in mice. Mechanistically, PPARD upregulates CCL20 and CXCL1 chemokines, increasing immune cell infiltration; a positive-feedback loop between PPARD and interferon gamma (IFNγ) signaling sustains gastric inflammation and drives VGPC transformation and tumorigenesis. Villin-PPARD transgenic mouse model, lineage-tracing experiments, cytokine/chemokine profiling, immunohistochemistry, transcriptome analysis, PPARD/IFNγ feedback loop characterization Gastroenterology High 30885780
2020 Conditional deletion of Ppard in CD11c+ cells attenuated atherosclerotic plaque formation and reduced activation and migration of myeloid-derived dendritic cells and T lymphocyte polarization to Th1. In bone marrow-derived DCs, Ppard deficiency reduced palmitic acid-induced upregulation of co-stimulatory molecules and pro-inflammatory cytokines IL-12 and TNFα, demonstrating that PPARδ activation by fatty acids mediates DC activation. Cre-loxP conditional knockout in ApoE-/- mice on high cholesterol diet, bone marrow-derived DC culture with palmitic acid, flow cytometry, cytokine measurements FASEB journal High 31919912
2025 Dietary lipid accumulation (oleic acid) in macrophages via CD36 leads to PPARδ (PPARD) release of the transcriptional repressor BCL6, which suppresses Il23a transcription in LPS-exposed macrophages. Deleting CD36 on macrophages restored IL-23 and IL-22 responses and reduced intestinal damage in HFD-fed DSS-treated mice. Conditional CD36 knockout in macrophages, DSS colitis model, oleic acid treatment of macrophages, LPS stimulation, IL-23/IL-22 measurements, PPARδ/BCL6 co-repressor complex characterization Scientific reports High 40717126
2025 H3K18 lactylation (H3K18la) promotes PPARD expression in breast cancer cells; PPARD in turn promotes transcription and phosphorylation of AKT (but not ILK), supporting cell survival under anaerobic glycolysis conditions. HDAC2 and HDAC3 act as erasers for H3 lysine lactylation upstream of PPARD. ChIP-seq with H3K18la antibodies, transcriptomics, proteomics, ATAC-seq, qPCR, western blot; HDAC2/3 identified as H3K18la erasers Cell death discovery Medium 39922804
2025 PPARD mediates transcriptional inhibition of MECP2 (methyl-CpG-binding protein 2), which in turn blocks STAT3 activation and alleviates Th17/Treg imbalance. PPARD knockdown-induced Th17/Treg imbalance was rescued by MECP2 deletion or STAT3 inhibition. PPARD siRNA knockdown, MECP2 deletion, STAT3 inhibition in vitro; rat CARAS model; Th17 differentiation assays Phytomedicine Medium 40031093
2025 PPARD activates PDK4 and ANGPTL4 expression in gastric smooth muscle cells (SMCs), leading to SMC dedifferentiation (phenotypic switching) under obese/lipid-excess conditions. Inhibition of PDK4 or ANGPTL4 upregulation prevented lipid-induced SMC modifications. High-fat diet mouse model, lipid-treated differentiated human gastric SMCs, siRNA-peptide nanoparticles for knockdown, pharmaceutical PPARD activation, global lipidomics and RNA sequencing, immunofluorescence, western blotting, validation in human obesity gastric samples Journal of biomedical science High 40652248
2025 ACSS2 promotes acetylation at the H3K27 site in the PPARD promoter region, increasing PPARD transcription, which in turn transcriptionally activates BCAT1 to alter branched-chain amino acid catabolism and promote pancreatic cancer proliferation and invasion. ACSS2 knockout, ChIP assays for H3K27 acetylation at PPARD promoter, qPCR/western blot for PPARD and BCAT1 expression, functional assays for proliferation and invasion Acta biochimica et biophysica Sinica Medium 40908872
2025 PPARD transcriptionally represses CDC20 by binding to its promoter; CDC20 downregulation inhibits proliferation of cisplatin-resistant cervical cancer cells, reduces Wnt/β-catenin pathway activity, and increases apoptosis. APS (Astragalus polysaccharide) promotes PPARD expression to suppress CDC20. Bioinformatics target prediction, ChIP for PPARD binding at CDC20 promoter, PPARD/CDC20 knockdown, Wnt/β-catenin pathway agonist rescue experiments, xenograft tumor model Cytotechnology Medium 40538591

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 NUC-1, a caenorhabditis elegans DNase II homolog, functions in an intermediate step of DNA degradation during apoptosis. Genes & development 139 10716942
2007 Identification and characterization of a selective peroxisome proliferator-activated receptor beta/delta (NR1C2) antagonist. Molecular endocrinology (Baltimore, Md.) 116 17975020
2007 Genetic variations in PPARD and PPARGC1A determine mitochondrial function and change in aerobic physical fitness and insulin sensitivity during lifestyle intervention. The Journal of clinical endocrinology and metabolism 108 17327385
1995 The human peroxisome proliferator-activated receptor (PPAR) subtype NUC1 represses the activation of hPPAR alpha and thyroid hormone receptors. The Journal of biological chemistry 80 7876127
1988 Sequence and expression of NUC1, the gene encoding the mitochondrial nuclease in Saccharomyces cerevisiae. Nucleic acids research 79 2836792
2015 Integrative and systemic approaches for evaluating PPARβ/δ (PPARD) function. Nuclear receptor signaling 75 25945080
2017 Metastasis regulation by PPARD expression in cancer cells. JCI insight 67 28097239
2011 A missense mutation in PPARD causes a major QTL effect on ear size in pigs. PLoS genetics 60 21573137
2008 Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study. The Journal of clinical endocrinology and metabolism 58 18252792
2006 Single nucleotide polymorphisms of PPARD in combination with the Gly482Ser substitution of PGC-1A and the Pro12Ala substitution of PPARG2 predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. Diabetes 58 16804087
2019 Pleiotropic Effects of PPARD Accelerate Colorectal Tumorigenesis, Progression, and Invasion. Cancer research 57 30679176
1994 Analysis of the role of the NUC1 endo/exonuclease in yeast mitochondrial DNA recombination. Current genetics 50 8087883
1993 Insertional mutagenesis in Neurospora crassa: cloning and molecular analysis of the preg+ gene controlling the activity of the transcriptional activator NUC-1. Genetics 47 8436269
1990 Molecular analysis of nuc-1+, a gene controlling phosphorus acquisition in Neurospora crassa. Molecular and cellular biology 46 2146493
2019 PPARD and Interferon Gamma Promote Transformation of Gastric Progenitor Cells and Tumorigenesis in Mice. Gastroenterology 44 30885780
1996 Translocation of Neurospora crassa transcription factor NUC-1 into the nucleus is induced by phosphorus limitation. Fungal genetics and biology : FG & B 43 8953266
2000 The C. elegans apoptotic nuclease NUC-1 is related in sequence and activity to mammalian DNase II. Gene 37 10903446
2010 Association of the CYBA, PPARGC1A, PPARG3, and PPARD gene variants with coronary artery disease and metabolic risk factors of coronary atherosclerosis in a Russian population. Heart and vessels 33 20512451
2008 Genetic study between SIRT1, PPARD, PGC-1alpha genes and Alzheimer's disease. Journal of neurology 33 18438697
2007 [Association of PPARD gene polymorphism with human physical performance]. Molekuliarnaia biologiia 32 18240567
2009 Is there an interaction between PPARD T294C and PPARGC1A Gly482Ser polymorphisms and human endurance performance? Experimental physiology 29 19666693
2025 Anaerobic metabolism promotes breast cancer survival via Histone-3 Lysine-18 lactylation mediating PPARD axis. Cell death discovery 26 39922804
2021 Keratinocyte-derived IL-1β induces PPARG downregulation and PPARD upregulation in human reconstructed epidermis following barrier impairment. Experimental dermatology 24 33683743
2012 Associations of type 2 diabetes with common variants in PPARD and the modifying effect of vitamin D among middle-aged and elderly Chinese. PloS one 21 22509365
2006 PPARD haplotype influences cholesterol metabolism but is no risk factor of Alzheimer's disease. Neuroscience letters 20 16979821
2015 Peroxisome Proliferator-activated Receptor-D (PPARD) Coordinates Mouse Spermatogenesis by Modulating Extracellular Signal-regulated Kinase (ERK)-dependent Signaling. The Journal of biological chemistry 19 26242735
2012 ACE I/D, ACTN3 R577X, PPARD T294C and PPARGC1A Gly482Ser polymorphisms and physical fitness in Taiwanese late adolescent girls. The journal of physiological sciences : JPS 18 22247001
2005 Developmental abnormalities in the Nuc1 rat retina: a spontaneous mutation that affects neuronal and vascular remodeling and retinal function. Neuroscience 18 16289888
1994 Analysis of the DNA-binding and dimerization activities of Neurospora crassa transcription factor NUC-1. Molecular and cellular biology 18 7969122
2017 Glabridin triggers over-expression of MCA1 and NUC1 genes in Candida glabrata: Is it an apoptosis inducer? Journal de mycologie medicale 17 28595940
2013 Genomic haplotype within the Peroxisome Proliferator-Activated Receptor Delta (PPARD) gene is associated with elite athletic status. Scandinavian journal of medicine & science in sports 17 24118591
2020 Ustilago maydis secreted T2 ribonucleases, Nuc1 and Nuc2 scavenge extracellular RNA. Cellular microbiology 16 32844528
2011 Peroxisome proliferator-activated receptor delta (PPARD) genetic variation and type 2 diabetes in middle-aged Chinese women. Annals of human genetics 16 21834910
1994 The sequence of a 36 kb segment on the left arm of yeast chromosome X identifies 24 open reading frames including NUC1, PRP21 (SPP91), CDC6, CRY2, the gene for S24, a homologue to the aconitase gene ACO1 and two homologues to chromosome III genes. Yeast (Chichester, England) 16 7754713
1988 The structural gene for a phosphorus-repressible phosphate permease in Neurospora crassa can complement a mutation in positive regulatory gene nuc-1. Molecular and cellular biology 15 2966896
2016 PPARD rs2016520 polymorphism is associated with metabolic traits in a large population of Chinese adults. Gene 13 26915488
2022 Identifying the Metabolic Signatures of PPARD-Overexpressing Gastric Tumors. International journal of molecular sciences 12 35163565
2018 The polymorphisms of the PPARD gene modify post-training body mass and biochemical parameter changes in women. PloS one 12 30157214
2012 The generation of oxidative stress-induced rearrangements in Saccharomyces cerevisiae mtDNA is dependent on the Nuc1 (EndoG/ExoG) nuclease and is enhanced by inactivation of the MRX complex. Mutation research 12 23276591
1993 Functional domains of the transcriptional activator NUC-1 in Neurospora crassa. Gene 12 8359693
2012 Investigation of polymorphic variants of PPARD and APOE genes in Turkish coronary heart disease patients. DNA and cell biology 11 22277050
2017 PPARD is an Inhibitor of Cartilage Growth in External Ears. International journal of biological sciences 10 28539839
2015 The Functional SNPs in the 5' Regulatory Region of the Porcine PPARD Gene Have Significant Association with Fat Deposition Traits. PloS one 10 26599230
2015 Serum from patients with ankylosing spondylitis can increase PPARD, fra-1, MMP7, OPG and RANKL expression in MG63 cells. Clinics (Sao Paulo, Brazil) 10 26602520
2013 p53 death signal is mainly mediated by Nuc1(EndoG) in the yeast Saccharomyces cerevisiae. FEMS yeast research 10 23875998
2012 Gene variants in PPARD and PPARGC1A are associated with timing of natural menopause in the general Japanese population. Maturitas 10 22310107
2022 Effects of PPARD gene variants on the therapeutic responses to exenatide in chinese patients with type 2 diabetes mellitus. Frontiers in endocrinology 9 36051387
2020 Pregnancy-associated changes of peroxisome proliferator-activated receptor delta (PPARD) and cytochrome P450 family 21 subfamily A member 2 (CYP21A2) expression in the bovine corpus luteum. The Journal of reproduction and development 9 32037375
2019 FSH3 mediated cell death is dependent on NUC1 in Saccharomyces cerevisiae. FEMS yeast research 9 30776074
2017 Glabridin induces overexpression of two major apoptotic genes, MCA1 and NUC1, in Candida albicans. Journal of global antimicrobial resistance 9 28844974
2013 The G32E functional variant reduces activity of PPARD by nuclear export and post-translational modification in pigs. PloS one 9 24058710
2022 Unraveling Gut Microbiota Signatures Associated with PPARD and PARGC1A Genetic Polymorphisms in a Healthy Population. Genes 7 35205333
2020 Deletion of Ppard in CD11c+ cells attenuates atherosclerosis in ApoE knockout mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 7 31919912
2019 PPARA, PPARD and PPARG gene polymorphisms in patients with unstable angina. Gene 7 31252163
2015 Positive association between PPARD rs2016520 polymorphism and coronary heart disease in a Han Chinese population. Genetics and molecular research : GMR 7 26125839
2013 Variants of the PPARD gene and their clinicopathological significance in colorectal cancer. PloS one 7 24391853
2024 Cell-Penetrating Chaperone Nuc1 for Small- and Large-Molecule Delivery Into Retinal Cells and Tissues. Investigative ophthalmology & visual science 6 39028980
2023 Nematodes Degrade Extracellular Antibiotic Resistance Genes by Secreting DNase II Encoded by the nuc-1 Gene. Environmental science & technology 6 37523858
2019 The Potential of the FSP1cre-Pparb/d-/- Mouse Model for Studying Juvenile NAFLD. International journal of molecular sciences 6 31618976
2018 Associations between hypertension and the peroxisome proliferator-activated receptor-δ (PPARD) gene rs7770619 C>T polymorphism in a Korean population. Human genomics 6 29914579
2017 Protective role of +294 T/C (rs2016520) polymorphism of PPARD in Mexican patients with colorectal cancer. Genetics and molecular research : GMR 6 28128413
2025 Jieyu Guben decoction alleviates combined allergic rhinitis and asthma syndrome by balancing Th17/Treg expression and restoring PPARD. Phytomedicine : international journal of phytotherapy and phytopharmacology 5 40031093
2021 PPARD May Play a Protective Role for Major Depressive Disorder. PPAR research 5 33968145
2019 Polymorphism of the PPARD Gene and Dynamic Balance Performance in Han Chinese Children. Hereditas 5 31148953
2018 Identification and characterization of cis-regulatory elements 'insulator and repressor' in PPARD gene. Epigenomics 5 29583017
2018 PPARD rs7770619 polymorphism in a Korean population: Association with plasma malondialdehyde and impaired fasting glucose or newly diagnosed type 2 diabetes. Diabetes & vascular disease research 5 29776318
2015 PPARD +294C overrepresentation in general and long-lived population in China Bama longevity area and unique relationships between PPARD +294T/C polymorphism and serum lipid profiles. Lipids in health and disease 5 25873088
2021 Association between peroxisome proliferator-activated receptor-alpha, -delta and -gamma gene (PPARA, PPARD, PPARG) polymorphisms and overweight parameters in physically active men. Biology of sport 4 35440841
2020 PPARD May Play a Protective Role against the Development of Schizophrenia. PPAR research 4 32831816
2025 Astragalus polysaccharide regulates the cervical cancer cell cycle and inhibits cisplatin resistance by blocking the Wnt/β-catenin pathway through the PPARD/CDC20 axis. Cytotechnology 3 40538591
2024 Variants in PPARD-GLP1R are related to diabetic kidney disease in Chinese Han patients with type 2 diabetes mellitus. Heliyon 3 39161836
2022 Haplotype of ESR1 and PPARD Genes Is Associated with Higher Anthropometric Changes in Han Chinese Obesity by Adjusting Dietary Factors-An 18-Month Follow-Up. Nutrients 3 36297109
2021 PPARD rs2016520 (T/C) and NOS1AP rs12742393 (A/C) polymorphisms affect therapeutic efficacy of nateglinide in Chinese patients with type 2 diabetes mellitus. BMC medical genomics 3 34772419
2012 [Effects of PPARD-87T > C and interactions with single nucleotide polymorphisms in PPARA and PPARG on abdominal obesity]. Zhonghua yi xue za zhi 3 22944052
2008 Use of the nuc1 null mutant for analysis of yeast mitochondrial nucleoids. The Journal of general and applied microbiology 3 19164874
2025 Obesity induces phenotypic switching of gastric smooth muscle cells through the activation of the PPARD/PDK4/ANGPTL4 pathway. Journal of biomedical science 2 40652248
2023 Protective Effects of a Mixed Medicinal Herb Extract (NUC1) on Collagenase-Induced Osteoarthritis in Rabbits. Journal of microbiology and biotechnology 2 37482815
2020 Single Nucleotide Polymorphisms in PPARD Associated with Systemic Lupus Erythematosus in Chinese Populations. Journal of immunology research 2 32566688
2025 Dietary lipids induce PPARd and BCL6 to repress macrophage IL-23 induction after intestinal injury and LPS exposure. Scientific reports 1 40717126
2025 The ACSS2-PPARD-BCAT1 axis synchronously regulates branched-chain amino acid metabolism and development in pancreatic cancer. Acta biochimica et biophysica Sinica 1 40908872
2025 Associations of genetic variants in the PPARD gene to racing performance in pigeons (Columba livia). Developmental biology 1 41429277
2023 Up-Regulated Expression of ICAM1, MT1A, PTGS2, LCE3D, PPARD, and GM-CSF2 Following Solar Skincare Protection and Repair Strategies in a 3-Dimensional Reconstructed Human Skin Model. Clinical, cosmetic and investigational dermatology 1 37850108
2022 Increased PPARD Expression May Play a Protective Role in Human Lung Adenocarcinoma and Squamous Cell Carcinoma. PPAR research 1 35342393
2026 The mitochondrial intermembrane space nuclease Nuc1 (endonuclease G) prevents mitophagy-mediated mtDNA escape in yeast. Current biology : CB 0 41638207
2026 Visceral obesity-induced METTL27 regulation of the FABP5/PPARD/CPT1A axis in promoting colorectal cancer progression. International journal of biological macromolecules 0 41651272
2026 gga-let-7c-3p Inhibits Chicken Abdominal Adipogenesis by Regulating PPARD Gene. Biomolecules 0 41750379
2026 Metabolic Checkpoints in Cutaneous Squamous Cell Carcinoma: ACSL1 and PPARD Orchestrate Lipid-Ferroptosis Crosstalk via Keratinocyte Remodeling. Applied biochemistry and biotechnology 0 42154143
2025 Contrastive sequence signatures between the both sides of a recombination spot reveal an adaptation at PPARD locus from standing variation for pleiotropy since out-of-Africa dispersal. BMC genomics 0 40307732
2025 pH-gated activation of nematodes-secreted NUC-1 accelerates extracellular antibiotic resistance gene degradation in aquatic environments. Water research 0 40349596
2025 Dietary lipids induce PPARd and BCL6 to repress macrophage IL-23 induction after intestinal injury and LPS exposure. Research square 0 40502773
2025 Construction of a deep learning model and identification of BSG, PPARD, and SLC16A8 expression as potential indicators in the context of strategies for precision therapy to acute myeloid leukemia. Hematology (Amsterdam, Netherlands) 0 41284982
2025 Curcumin Activates the Wnt/β-Catenin/PPARD Signaling Axis to Attenuate Ochratoxin A-Induced Enterotoxicity. Journal of agricultural and food chemistry 0 41439788

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