Affinage

PARP14

Protein mono-ADP-ribosyltransferase PARP14 · UniProt Q460N5

Length
1801 aa
Mass
202.8 kDa
Annotated
2026-04-29
64 papers in source corpus 33 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PARP14 is a multidomain mono-ADP-ribosyltransferase (MARylase) that integrates innate immune signaling, transcriptional regulation, metabolic reprogramming, and genome maintenance through its enzymatic writer, reader, and eraser activities. Its catalytic domain MARylates STAT1, HDAC2/3, RACK1, GLUD1, and SQSTM1/p62, while macrodomains 2 and 3 read mono-ADP-ribosylation marks and macrodomain 1 functions as an ADP-ribosylhydrolase whose activity is mimicked and counteracted by coronavirus macrodomains (PMID:37703374, PMID:23473667, PMID:21081493, PMID:27796300, PMID:40195501). PARP14 acts as a transcriptional switch downstream of IL-4/STAT6 by ADP-ribosylating HDACs to derepress target promoters, cross-regulates macrophage polarization by suppressing STAT1 phosphorylation, promotes Th17 differentiation, and upon IFN-γ stimulation drives formation of cytoplasmic p62 body condensates enriched in ADP-ribosylated substrates and polyubiquitin chains (PMID:21081493, PMID:27796300, PMID:23956424, PMID:38834853, PMID:40195501). In genome maintenance, PARP14 interacts with PCNA and uses its RRM domains to recruit MRE11 to reversed replication forks in BRCA-deficient cells, promoting nascent strand degradation, while its loss creates synthetic lethality with the ATR-CHK1 pathway; PARP14 also stabilizes cyclin D1 and tissue factor mRNAs through 3′UTR-dependent mechanisms and inhibits JNK1 to sustain aerobic glycolysis and tumor cell survival (PMID:36030235, PMID:41684642, PMID:32542389, PMID:34158578, PMID:25293769, PMID:25258887).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2009 High

    Before this work, the biological role of PARP14 was unknown; this study established it as a STAT6 binding partner that mediates IL-4-dependent survival in B cells and influences lymphomagenesis, placing it in adaptive immune signaling.

    Evidence PARP14 knockout mice, co-immunoprecipitation with STAT6, apoptosis assays in primary B cells

    PMID:19147789

    Open questions at the time
    • Enzymatic activity not yet linked to STAT6 function
    • Downstream transcriptional mechanism unknown
  2. 2010 High

    Resolving how PARP14 controls transcription, this work showed it acts as a bimodal switch: recruiting HDAC2/3 to repress IL-4-responsive promoters basally, then ADP-ribosylating those HDACs upon IL-4 stimulation to derepress gene expression and enable STAT6 binding.

    Evidence ChIP, co-immunoprecipitation, ADP-ribosylation assays, luciferase reporters

    PMID:21081493

    Open questions at the time
    • Specific HDAC residues modified not identified
    • Whether other STAT6-target promoters use the same switch unknown
  3. 2011 High

    Extending PARP14's role beyond transcription, its requirement for IL-4-induced glycolysis in B cells was established, linking its activity to metabolic reprogramming and Myc-driven lymphomagenesis.

    Evidence PARP14 KO mice, glycolysis assays, AMPK activity measurement, E-Myc lymphoma model

    PMID:21911376

    Open questions at the time
    • Direct enzymatic substrates mediating glycolytic control not identified
    • Relationship to JNK1 axis not yet established
  4. 2012 High

    PARP14 was identified as a JNK2-dependent pro-survival effector in multiple myeloma that directly binds and inhibits pro-apoptotic JNK1, revealing a non-catalytic scaffolding function in tumor cell survival.

    Evidence Reciprocal co-IP of PARP14-JNK1, siRNA knockdown, overexpression rescue in myeloma cells

    PMID:23045269

    Open questions at the time
    • Whether JNK1 inhibition requires PARP14 catalytic activity unknown
    • Structural basis of PARP14-JNK1 interaction not determined
  5. 2013 High

    Two advances defined PARP14 as both a reader of mono-ADP-ribosylation and an immune regulator beyond B cells: crystal structures showed macrodomains 2/3 selectively bind mono-ADP-ribosylated substrates, and KO studies revealed PARP14 catalytic activity drives Th17 differentiation and IgE responses.

    Evidence X-ray crystallography and ITC of macrodomains 2/3; PARP14 KO mice with T cell differentiation assays and antibody measurements

    PMID:23473667 PMID:23956424

    Open questions at the time
    • In vivo reader substrates not identified
    • How macrodomain reading integrates with transferase activity unclear
  6. 2014 High

    PARP14 was shown to regulate mRNA stability by forming an RNP complex with tristetraprolin on the tissue factor 3′UTR, and to form a functional complex with DTX3L and PARP9/ARTD9 in cancer cells, broadening its molecular partnerships.

    Evidence RIP and RNA pull-down for TTP-TF mRNA interaction with KO mouse validation; Co-IP of PARP14-DTX3L-ARTD9 in prostate cancer cells

    PMID:24886089 PMID:25293769

    Open questions at the time
    • Whether PARP14 catalytic activity is needed for mRNA regulation not tested
    • Stoichiometry and structural basis of the DTX3L/PARP9/PARP14 complex unresolved
  7. 2015 High

    Two parallel advances established PARP14 in genome maintenance and metabolic signaling: PARP14 interacts with PCNA and promotes homologous recombination at replication forks, and it sustains the Warburg effect by inhibiting JNK1 to prevent PKM2 Thr365 phosphorylation.

    Evidence Co-IP of PARP14-PCNA, RAD51 foci and DNA damage sensitivity in KD cells; JNK1-PKM2 phosphorylation epistasis in HCC cells and xenografts

    PMID:25753673 PMID:26258887

    Open questions at the time
    • Whether PCNA interaction requires PARP14 catalytic activity not determined
    • Direct MARylation targets at replication forks unknown
  8. 2016 High

    PARP14 was shown to directly ADP-ribosylate STAT1, suppressing its phosphorylation and thereby cross-regulating macrophage polarization between pro- and anti-inflammatory states, with PARP9 acting as its functional antagonist.

    Evidence Proteomics, site-directed mutagenesis of STAT1 ADP-ribosylation sites, phosphorylation analysis in primary macrophages

    PMID:27796300

    Open questions at the time
    • Precise STAT1 modification sites not fully mapped
    • How PARP9 reverses the modification mechanistically unresolved
  9. 2018 High

    Chemical genetic substrate identification revealed PARP14 MARylates >100 proteins enriched for RNA regulatory functions, including direct modification of PARP13, while nuclear translocation studies showed PARP14 promotes accumulation of ISG-encoded proteins and IFN-β transcription in macrophages.

    Evidence Orthogonal NAD+ analog chemical genetics with BioID and MS; nuclear fractionation and MS interactomics with siRNA knockdown in macrophages

    PMID:29500242 PMID:30247868

    Open questions at the time
    • Functional consequence of PARP13 MARylation unknown
    • How PARP14 promotes nuclear accumulation of ISG products mechanistically unclear
  10. 2020 High

    Genome-wide CRISPR screening identified synthetic lethality between PARP14 loss and ATR-CHK1 pathway inhibition, defining PARP14 as a modulator of replication dynamics and a potential therapeutic vulnerability.

    Evidence Genome-wide CRISPR KO screen, DNA fiber assays, ATR/CHK1 inhibitor sensitivity

    PMID:32542389

    Open questions at the time
    • Whether synthetic lethality depends on PARP14 catalytic or structural function not resolved
    • Patient-relevant contexts not tested
  11. 2021 High

    PARP14 was found to stabilize cyclin D1 mRNA via its 3′UTR, controlling G1/S cell cycle progression through the RB and p53-p21 pathways, establishing it as a cell cycle regulator.

    Evidence Luciferase 3′UTR reporter, siRNA knockdown, cell cycle analysis by flow cytometry

    PMID:34158578

    Open questions at the time
    • Direct RNA-binding domain responsible not mapped
    • Whether MARylation of an RNA-binding protein mediates this effect unknown
  12. 2022 High

    PARP14's replication fork role was mechanistically refined: it is recruited to nascent DNA upon replication stress in BRCA-deficient cells and its catalytic activity mediates MRE11 engagement via the KU complex, promoting fork degradation and ssDNA gap formation.

    Evidence iPOND, DNA fiber assay, proximity ligation assay, catalytic inhibitor and siRNA in BRCA-deficient cells

    PMID:36030235

    Open questions at the time
    • Direct MARylation substrates at the fork not identified
    • Which domain recruits to nascent DNA not yet mapped
  13. 2023 High

    The discovery that PARP14 macrodomain 1 is an active ADP-ribosylhydrolase established PARP14 as a dual writer-eraser enzyme, and revealed that coronavirus macrodomains (e.g., SARS-CoV-2 Mac1) functionally mimic this eraser activity to counteract host MARylation.

    Evidence In vitro hydrolase assays, F926A mutagenesis ablating activity, cellular MARylation accumulation upon macrodomain 1 inactivation, reconstitution with SARS-CoV-2 Mac1

    PMID:37507011 PMID:37703374

    Open questions at the time
    • Physiological substrates preferentially de-MARylated by macrodomain 1 not identified
    • Structural basis for substrate selectivity of macrodomain 1 vs. viral Mac1 not resolved
  14. 2024 High

    Multiple studies converged to show that IFN-γ-induced PARP14 is the dominant MARylase in macrophages, regulated post-translationally by PARP9/DTX3L, and that its activity and physical presence drive formation of p62 body condensates containing ADP-ribosylated substrates including p62 itself, polyubiquitin, and selective autophagy receptors—structures counteracted by SARS-CoV-2 Mac1.

    Evidence Improved MAR antibodies, PARP14/PARP9/DTX3L KD, immunofluorescence, site-directed mutagenesis of p62 cysteine acceptor residues, proteasome/autophagy inhibitors

    PMID:38834852 PMID:38834853 PMID:40195501

    Open questions at the time
    • Functional consequence of p62 body condensates for antiviral defense not established
    • Whether condensate formation occurs in vivo during infection unknown
    • Cysteine-directed MARylation specificity mechanism not structurally resolved
  15. 2024 Medium

    KH-like domains were identified as the structural determinants mediating PARP14-DTX3L and PARP9-DTX3L protein-protein interactions, with DTX3L binding shifting PARP14 activity from auto- to trans-MARylation.

    Evidence Co-IP with KH domain mutagenesis, in vitro ADP-ribosylation assays

    PMID:38182103

    Open questions at the time
    • Structural model of the ternary PARP14-PARP9-DTX3L complex absent
    • In vivo relevance of the auto- to trans-MARylation switch unconfirmed
  16. 2025 High

    Domain-specific analysis showed PARP14's RRM domains are necessary and sufficient for recruitment to reversed replication forks in BRCA2-deficient cells and for subsequent MRE11 engagement, resolving the structural basis of its replication fork function.

    Evidence iPOND with RRM truncation/mutation, MRE11 recruitment and DNA fiber assays in BRCA2-deficient cells

    PMID:41684642

    Open questions at the time
    • Whether RRM domains bind DNA or RNA at the fork not distinguished
    • RRM-mediated interaction partners beyond MRE11 not mapped
  17. 2025 High

    PARP14 was shown to restrict coronavirus (MHV, SARS-CoV-2 with Mac1 mutation) and HSV-1 replication while paradoxically enhancing VSV replication, with antiviral effects on coronaviruses depending on catalytic activity and others being catalytic-activity-independent.

    Evidence PARP14 KO cells, catalytic inhibitor, viral replication assays across five viruses, IFN production measurement

    PMID:40937852

    Open questions at the time
    • Direct antiviral MARylation substrates not identified
    • Mechanism of catalytic-activity-independent HSV-1 restriction unknown
    • Basis for proviral activity toward VSV not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the full catalog of physiological MARylation substrates that drive specific PARP14 functions, the structural basis for how PARP14 macrodomain 1 hydrolase and catalytic domain transferase activities are coordinated, and whether PARP14-dependent p62 body condensates serve a direct antiviral effector function in vivo.
  • No structural model of full-length PARP14
  • In vivo antiviral mechanism through MARylation not demonstrated
  • Coordination between hydrolase and transferase domains within the same polypeptide not mechanistically explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 9 GO:0003723 RNA binding 4 GO:0140110 transcription regulator activity 3 GO:0016787 hydrolase activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-168256 Immune System 6 R-HSA-1430728 Metabolism 4 R-HSA-73894 DNA Repair 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 1
Partners
DTX3LHDAC2JNK1MRE11PARP9PCNASTAT1STAT6
Complex memberships
PARP14-PARP9-DTX3L complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 PARP-14 functions as a transcriptional switch for STAT6-dependent gene activation: under non-stimulating conditions it recruits HDAC2 and HDAC3 to IL-4-responsive promoters to repress transcription; upon IL-4 stimulation, PARP-14 ADP-ribosylates the HDACs causing their release, promotes STAT6 binding to target promoters, and allows replacement by HAT-containing coactivators. Chromatin immunoprecipitation, co-immunoprecipitation, ADP-ribosylation assays, luciferase reporter assays, loss-of-function studies The Journal of biological chemistry High 21081493
2009 PARP-14 is a binding partner of the IL-4-induced transcription factor STAT6 and mediates IL-4-dependent protection against apoptosis in primary B cells, regulating gene products controlling cell survival, proliferation, and lymphomagenesis. PARP-14 knockout mice, co-immunoprecipitation, apoptosis assays, gene expression analysis Blood High 19147789
2011 PARP-14 is required for IL-4-induced enhancement of glycolysis in B cells; this glycolytic activity is central to IL-4-mediated prosurvival signaling, and PARP14 deficiency delays B lymphomagenesis driven by the Myc oncogene. Parp14 knockout mice, glycolysis assays, AMPK activity measurement, Myc-driven lymphoma model Proceedings of the National Academy of Sciences of the United States of America High 21911376
2012 PARP14 is a critical effector of JNK2-dependent prosurvival signaling in multiple myeloma: constitutively active JNK2 maintains PARP14 expression, PARP14 binds and inhibits pro-apoptotic JNK1, and PARP14 overexpression rescues myeloma cells from apoptosis induced by JNK2 knockdown. Loss-of-function (siRNA), overexpression rescue experiments, co-immunoprecipitation (PARP14-JNK1 binding), apoptosis assays Oncogene High 23045269
2013 PARP14 macrodomains 2 and 3 (ARTD8/PARP14) function as readers of mono-ADP-ribosylated substrates: crystal structures of these macrodomains confirmed ADP-ribose binding, they recognized mono-ADP-ribosylated ARTD10 and its substrate Ran but not poly-ADP-ribosylated ARTD1, and ARTD10 colocalized with ARTD8 in cells. Crystal structure determination, isothermal titration calorimetry, in vitro binding assays, cell colocalization Structure (London, England : 1993) High 23473667
2014 PARP14 forms a ribonucleoprotein complex with the mRNA-destabilizing protein tristetraprolin (TTP) and a conserved AU-rich element in the tissue factor (TF) mRNA 3′UTR, selectively regulating TF mRNA stability in macrophages; PARP14 deficiency increases TF mRNA stability, TF expression, and coagulation activity in vitro and in vivo. Ribonucleoprotein complex immunoprecipitation, biotinylated RNA pull-down, Parp14 knockout mice, mRNA stability assays Blood High 25293769
2014 PARP14 (ARTD8) forms complexes with DTX3L and ARTD9 in metastatic prostate cancer cells, and its enzymatic (ADP-ribosyltransferase) activity is required for survival of these cells; the complex also regulates IRF1 expression. Co-immunoprecipitation, immunofluorescence, siRNA loss-of-function, cell survival and proliferation assays Molecular cancer Medium 24886089
2015 PARP14 promotes aerobic glycolysis (Warburg effect) in hepatocellular carcinoma by maintaining low PKM2 activity: PARP14 inhibits pro-apoptotic JNK1 kinase, which would otherwise phosphorylate PKM2 at Thr365 and activate it; loss of PARP14 leads to JNK1 activation, PKM2 phosphorylation, and reduced glycolysis/increased apoptosis. Loss-of-function studies (siRNA/shRNA) in vitro and in vivo (xenografts), PKM2 phosphorylation assays, glycolysis measurements, JNK1 activity assays Nature communications High 26258887
2015 PARP14 (mono-ADP-ribosyltransferase) interacts with PCNA and promotes homologous recombination DNA repair; PARP14 depletion results in reduced HR, persistent RAD51 foci, hypersensitivity to DNA-damaging agents, and accumulation of DNA strand breaks, establishing a role in replication fork stability and common fragile site replication. Co-immunoprecipitation (PARP14-PCNA interaction), siRNA knockdown, DNA damage sensitivity assays, RAD51 foci analysis, comet assay Nucleic acids research High 25753673
2016 PARP14 and PARP9 cross-regulate macrophage activation: PARP14 directly ADP-ribosylates STAT1, which suppresses STAT1 phosphorylation; PARP9 counteracts this modification. Mutations at PARP14-dependent ADP-ribosylation sites on STAT1 lead to increased STAT1 phosphorylation. PARP14 also promotes STAT6 phosphorylation and anti-inflammatory gene expression in M(IL-4) macrophages. Global proteomics, siRNA knockdown, ADP-ribosylation assays, site-directed mutagenesis of STAT1 ADP-ribosylation sites, phosphorylation analysis, primary macrophages Nature communications High 27796300
2018 Using a chemical genetics approach (orthogonal NAD+ analog) combined with BioID proximity labeling, PARP14 was shown to MARylate 114 specific protein substrates, several of which are RNA regulatory proteins; PARP13 is directly MARylated by PARP14 on several acidic amino acids, revealing crosstalk between PARP family members. Chemical genetics (engineered PARP14 with orthogonal NAD+ analog), BioID proximity labeling, mass spectrometry, in vitro MARylation assays ACS chemical biology High 30247868
2018 PARP14 translocates into the nucleus of macrophages stimulated with inflammatory stimuli, binds a group of IFN-stimulated gene (ISG)-encoded proteins (identified by quantitative mass spectrometry), and is required for their nuclear accumulation; PARP14 depletion also attenuates transcription of primary antiviral response genes including Ifnb1, reducing IFN-β production. Nuclear fractionation/translocation assays, quantitative mass spectrometry, siRNA knockdown, gene expression analysis, Salmonella infection assay Journal of immunology (Baltimore, Md. : 1950) High 29500242
2020 PARP14 suppresses microglial activation post-stroke by transcriptionally repressing the Lpar5 (lysophosphatidic acid receptor 5) gene; overexpression of PARP14 reduces LPAR5 expression and alleviates microglial activation, while PARP14 knockdown increases activation and worsens stroke outcomes. Photothrombotic stroke mouse model, PARP14 overexpression/knockdown, microglial activation assays, gene expression analysis, pharmacological inhibition Autophagy Medium 33317392
2020 Genome-wide CRISPR screen in PARP14-deficient cells identified the ATR-CHK1 pathway as synthetically lethal with PARP14 loss; PARP14 modulates DNA replication dynamics, and its loss sensitizes cells to ATR-CHK1 pathway inhibitors. Genome-wide CRISPR knockout screen, DNA fiber assay (replication dynamics), ATR/CHK1 inhibitor sensitivity assays Nucleic acids research High 32542389
2021 PARP14 regulates cyclin D1 mRNA stability through the cyclin D1 3′UTR, controlling cyclin D1 protein levels; depletion of PARP14 reduces cyclin D1, causes G1 cell-cycle arrest dependent on an intact RB pathway, and requires the p53-p21 pathway for arrest. siRNA knockdown, luciferase 3′UTR stability assays, cell cycle analysis (flow cytometry), Western blot Oncogene High 34158578
2022 PARP14 is a critical cofactor of MRE11 at stalled replication forks in BRCA-deficient cells: PARP14 is recruited to nascent DNA upon replication stress, and through its catalytic (mono-ADP-ribosyltransferase) activity mediates MRE11 engagement, promoting fork degradation and ssDNA gap accumulation; the KU complex recruits the PARP14-MRE11 complex to initiate partial resection. DNA fiber assay, iPOND (isolation of proteins on nascent DNA), siRNA/catalytic inhibitor studies, proximity ligation assay, Co-immunoprecipitation Nature communications High 36030235
2023 PARP14 is a dual-function enzyme with both ADP-ribosyl transferase and hydrolase (de-MARylase) activities: the PARP14 macrodomain 1 is an active ADP-ribosyl glycohydrolase acting on protein and nucleic acid substrates; inactivation of macrodomain 1 causes marked accumulation of MARylation (including on PARP14 itself and PARP13) in human cells; SARS-CoV-2 Mac1 reverses PARP14-mediated ADP-ribosylation in vitro and in cells. In vitro ADP-ribosylhydrolase activity assays, site-directed mutagenesis (macrodomain 1 inactivation), cell-based MARylation detection, reconstitution with SARS-CoV-2 Mac1 Science advances High 37703374
2023 PARP14 macrodomain 1 and PARP9 macrodomain 1 both display ADP-ribosyl glycohydrolase activity that is not directed toward specific protein side chains; PARP14 macrodomain 1 cannot degrade poly(ADP-ribose); the F926A mutation of PARP14 macrodomain 1 strongly reduces hydrolase activity, mechanistically analogous to SARS-CoV-2 Nsp3 Mac1. Biochemical ADP-ribosylation/hydrolysis assays, site-directed mutagenesis (F926A), comparison with Mac1 domain The Journal of biological chemistry High 37507011
2024 Interferon-γ-induced ADP-ribosylation in macrophages depends on PARP14 as the major catalytic enzyme; the PARP9/DTX3L complex regulates PARP14 protein levels via post-translational mechanisms and modulates PARP14 ADP-ribosylation activity; PARP14 and DTX3L localize to IFNγ-induced cytoplasmic inclusions containing ADP-ribosylated proteins; SARS-CoV-2 Mac1 reverses PARP14-dependent ADP-ribosylation. Improved mono-ADP-ribosylation antibody detection, PARP14/PARP9/DTX3L knockdown, immunofluorescence localization, in vitro hydrolysis by Mac1, mass spectrometry The EMBO journal High 38834852 38834853
2024 KH-like domains in PARP14 and in PARP9/DTX3L mediate protein-protein interactions: KH domains coordinate PARP9-DTX3L and PARP14-DTX3L interactions; DTX3L homodimerization is coordinated by its KH-like domain; in vitro, DTX3L interaction suppresses PARP14 auto-ADP-ribosylation and promotes trans-ADP-ribosylation of PARP9 and DTX3L. Co-immunoprecipitation, site-directed mutagenesis of KH domain, in vitro ADP-ribosylation assays, cell survival assays with truncation constructs Journal of molecular biology Medium 38182103
2024 Interferon-induced PARP14 mono-ADP-ribosylates SQSTM1/p62 at cysteine residues 113, 289/290, and 331; this modification occurs in cytoplasmic p62 foci that colocalize with ubiquitin and PARP14 but not LC3 (autophagosome marker); SARS-CoV-2 macrodomain prevents this p62 modification, and TRIM21 prevents autophagic degradation of ADP-ribosylated p62. Site-specific mutagenesis of p62 cysteine residues, immunofluorescence colocalization, in vitro MARylation, SARS-CoV-2 macrodomain treatment, TRIM21 knockdown bioRxiv (preprint)preprint Medium bio_10.1101_2024.06.29.601315
2024 Interferon-induced PARP14-mediated ADP-ribosylation occurs in p62 body condensates: PARP14 physical presence and catalytic activity are both required for condensate formation; these condensates contain p62, NBR1, TAX1BP1, and K48/K63-linked polyubiquitin chains but lack LC3B; condensate formation requires an active ubiquitin-proteasome system but not autophagy. PARP14 knockdown/catalytic mutant, immunofluorescence colocalization, p62 knockdown, autophagy inhibitors, proteasome inhibitors, ubiquitin pathway perturbations The EMBO journal High 40195501
2024 PARP14 mono-ADP-ribosylates RACK1 (an integral ribosome component) on three acidic residues, promoting stress granule formation and colocalization of RACK1 with G3BP1, eIF3η, and 40S ribosomal proteins; MARylation of RACK1 reduces translation of a subset of mRNAs including AKT; the ADP-ribosyl hydrolase TARG1 de-MARylates RACK1 to disassemble stress granules and restore translation. In vitro MARylation assay, site-directed mutagenesis of RACK1 acceptor residues, PARP14 inhibitor treatment, stress granule imaging, polysome profiling, in vivo tumor growth assays bioRxiv (preprint)preprint Medium 37873085
2022 PARP14 promotes EP4 receptor expression in colon cancer cells by mono-ADP-ribosylating HDAC1 and HDAC2; suppression of PARP14 by siRNA or inhibitors reduces EP4 receptor mRNA and protein expression. siRNA knockdown, PARP14 inhibitors, Western blot, RT-PCR for EP4 receptor expression Biochemical and biophysical research communications Medium 35914351
2013 PARP14 catalytic activity is required for Th17 cell differentiation downstream of T cell activation; PARP14 deficiency reduces IgE responses via a B cell-intrinsic process involving STAT6, and reduces IgA through B cell-extrinsic effects involving Th17 cells and CD103+ DCs; PARP14 enhances expression of RORα, Runx1, and Smad3 after T cell activation. PARP14 knockout mice, adoptive transfer experiments, antibody response measurements, T cell differentiation assays, catalytic activity requirement tested Journal of immunology (Baltimore, Md. : 1950) High 23956424
2026 PARP14 RRM (RNA Recognition Motif) domains mediate recruitment of PARP14 to nascent DNA at reversed replication forks in BRCA2-deficient cells; these RRM domains are necessary for MRE11 recruitment to reversed forks, nascent strand degradation, and replication stress-induced double-strand break formation. iPOND (isolation of proteins on nascent DNA), RRM domain truncation/mutation analysis, MRE11 recruitment assays, DNA fiber assay, DSB formation assays in BRCA2-deficient cells NAR cancer High 41684642
2022 PARP14 promotes AML cell proliferation and glycolysis by activating NF-κB signaling to promote HIF-1α expression; HIF-1α silencing reverses the pro-cancer effects of PARP14, and PARP14 promotes tumor formation in vivo. siRNA knockdown, NF-κB inhibitor (BAY11-7082), Western blot, proliferation/apoptosis assays, glycolysis measurements, xenograft model Clinical immunology (Orlando, Fla.) Medium 35944879
2025 PARP14 catalytic activity enhances IFN-β and IFN-λ responses and independently restricts coronavirus (MHV and SARS-CoV-2 ARH-deficient) and HSV-1 replication; PARP14 also enhances VSV replication (proviral function); the effects on HSV-1 and VSV are independent of PARP14 catalytic activity. PARP14 KO cells, PARP14 active site inhibitor, viral replication assays (MHV, SARS-CoV-2, HSV-1, VSV, LCMV), IFN production measurement mBio High 40937852
2024 PARP14 inhibits GLUD1 (glutamate dehydrogenase 1) activity through mono-ADP-ribosylation, reducing alpha-ketoglutarate (α-KG) production and suppressing energy metabolism in granulosa cells; this PARP14-GLUD1-α-KG axis is involved in ovarian cell apoptosis regulation. Co-immunoprecipitation (PARP14-GLUD1 interaction), in vitro MARylation assay, GLUD1 activity assay, metabolite measurement (α-KG), PARP14 knockdown/overexpression Phytomedicine Medium 41895093
2025 PARP14 positively regulates NNT (nicotinamide nucleotide transhydrogenase) expression in microglia; NNT deficiency leads to ROS accumulation and microglial inflammation; PARP14 alleviates microglial activation and depressive-like behaviors in CUS mice via NNT-mediated ROS clearance. Hippocampal PARP14 overexpression (viral vector), NNT overexpression rescue, ROS inhibitor (N-Acetylcysteine), microglial activation assays, behavioral tests Brain, behavior, and immunity Medium 39978699
2025 PARP14 enhances SOCS2 mRNA stability in macrophages; overexpression of PARP14 restores M2 polarization suppressed by botulinum toxin A (BTXA), while SOCS2 silencing counteracts this; BTXA inhibits the PARP14-SOCS2 axis to reduce M2 macrophage polarization. RNA sequencing, mRNA stability assays, PARP14/SOCS2 overexpression and silencing, M2 polarization assays, mouse HS model Biochimica et biophysica acta. Molecular cell research Medium 40505894
2025 YTHDF2 (m6A reader) binds Parp14 mRNA under oxygen-glucose deprivation conditions and reduces its stability via m6A-dependent mechanisms, decreasing PARP14 protein levels; YTHDF2 knockdown prevents PARP14 downregulation and promotes PARP14-driven microglial M1→M2 phenotypic switch. RIP (YTHDF2-Parp14 mRNA interaction), mRNA stability assays, siRNA knockdown of YTHDF2, microglial polarization assays Journal of neuroimmunology Medium 40383033

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation. Nature communications 233 27796300
2015 PARP14 promotes the Warburg effect in hepatocellular carcinoma by inhibiting JNK1-dependent PKM2 phosphorylation and activation. Nature communications 187 26258887
2010 PARP-14 functions as a transcriptional switch for Stat6-dependent gene activation. The Journal of biological chemistry 121 21081493
2013 Recognition of mono-ADP-ribosylated ARTD10 substrates by ARTD8 macrodomains. Structure (London, England : 1993) 110 23473667
2014 DTX3L and ARTD9 inhibit IRF1 expression and mediate in cooperation with ARTD8 survival and proliferation of metastatic prostate cancer cells. Molecular cancer 95 24886089
2012 Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma. Oncogene 94 23045269
2011 Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family. Proceedings of the National Academy of Sciences of the United States of America 91 21911376
2009 PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells. Blood 84 19147789
2018 PARP14 Controls the Nuclear Accumulation of a Subset of Type I IFN-Inducible Proteins. Journal of immunology (Baltimore, Md. : 1950) 75 29500242
2020 PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery. Autophagy 61 33317392
2014 PARP-14 combines with tristetraprolin in the selective posttranscriptional control of macrophage tissue factor expression. Blood 61 25293769
2015 Identification of a novel PARP14-TFE3 gene fusion from 10-year-old FFPE tissue by RNA-seq. Genes, chromosomes & cancer 56 26032162
2018 Combining Chemical Genetics with Proximity-Dependent Labeling Reveals Cellular Targets of Poly(ADP-ribose) Polymerase 14 (PARP14). ACS chemical biology 55 30247868
2023 PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities. Science advances 54 37703374
2015 A novel role for the mono-ADP-ribosyltransferase PARP14/ARTD8 in promoting homologous recombination and protecting against replication stress. Nucleic acids research 52 25753673
2021 PARP14 regulates cyclin D1 expression to promote cell-cycle progression. Oncogene 43 34158578
2019 Research Progress on PARP14 as a Drug Target. Frontiers in pharmacology 39 30890936
2022 The KU-PARP14 axis differentially regulates DNA resection at stalled replication forks by MRE11 and EXO1. Nature communications 38 36030235
2024 PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation. The EMBO journal 36 38834853
2019 A Study into the ADP-Ribosylome of IFN-γ-Stimulated THP-1 Human Macrophage-like Cells Identifies ARTD8/PARP14 and ARTD9/PARP9 ADP-Ribosylation. Journal of proteome research 31 30848916
2013 B cell-intrinsic and -extrinsic regulation of antibody responses by PARP14, an intracellular (ADP-ribosyl)transferase. Journal of immunology (Baltimore, Md. : 1950) 31 23956424
2023 PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models. Nature communications 30 37752135
2022 PARP14 promotes the growth and glycolysis of acute myeloid leukemia cells by regulating HIF-1α expression. Clinical immunology (Orlando, Fla.) 30 35944879
2019 PARP14 promotes the proliferation and gemcitabine chemoresistance of pancreatic cancer cells through activation of NF-κB pathway. Molecular carcinogenesis 29 30968979
2020 Genome-wide CRISPR synthetic lethality screen identifies a role for the ADP-ribosyltransferase PARP14 in DNA replication dynamics controlled by ATR. Nucleic acids research 26 32542389
2023 PARP14 is a writer, reader, and eraser of mono-ADP-ribosylation. The Journal of biological chemistry 25 37507011
2008 The macroPARP genes Parp-9 and Parp-14 are developmentally and differentially regulated in mouse tissues. Developmental dynamics : an official publication of the American Association of Anatomists 25 18069692
2024 PARP14 is regulated by the PARP9/DTX3L complex and promotes interferon γ-induced ADP-ribosylation. The EMBO journal 24 38834852
2024 KH-like Domains in PARP9/DTX3L and PARP14 Coordinate Protein-Protein Interactions to Promote Cancer Cell Survival. Journal of molecular biology 23 38182103
2023 Mono-ADP-ribosylation by PARP10 and PARP14 in genome stability. NAR cancer 23 36814782
2018 Discovery of a novel allosteric inhibitor scaffold for polyadenosine-diphosphate-ribose polymerase 14 (PARP14) macrodomain 2. Bioorganic & medicinal chemistry 23 29567296
2017 Identification of PARP14 inhibitors using novel methods for detecting auto-ribosylation. Biochemical and biophysical research communications 23 28315326
2018 Structure, Function and Inhibition of Poly(ADP-ribose)polymerase, Member 14 (PARP14). Mini reviews in medicinal chemistry 21 30112992
2022 PARP14 is a novel target in STAT6 mutant follicular lymphoma. Leukemia 20 35851155
2021 Targeted Degradation of PARP14 Using a Heterobifunctional Small Molecule. Chembiochem : a European journal of chemical biology 17 33838082
2023 FHL2 regulates microglia M1/M2 polarization after spinal cord injury via PARP14-depended STAT1/6 pathway. International immunopharmacology 15 37708708
2024 Targeting PARP14 with lomitapide suppresses drug resistance through the activation of DRP1-induced mitophagy in multiple myeloma. Cancer letters 12 38467180
2025 Interferon-induced PARP14-mediated ADP-ribosylation in p62 bodies requires the ubiquitin-proteasome system. The EMBO journal 11 40195501
2025 PARP14 is an interferon (IFN)-induced host factor that promotes IFN production and affects the replication of multiple viruses. bioRxiv : the preprint server for biology 10 38712082
2024 Pterosin B improves cognitive dysfunction by promoting microglia M1/M2 polarization through inhibiting Klf5/Parp14 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 10 39413455
2022 PARP14 regulates EP4 receptor expression in human colon cancer HCA-7 cells. Biochemical and biophysical research communications 10 35914351
2022 Selective Pharmaceutical Inhibition of PARP14 Mitigates Allergen-Induced IgE and Mucus Overproduction in a Mouse Model of Pulmonary Allergic Response. ImmunoHorizons 9 35817532
2024 Two ferroptosis-specific expressed genes NOX4 and PARP14 are considered as potential biomarkers for the diagnosis and treatment of diabetic retinopathy and atherosclerosis. Diabetology & metabolic syndrome 7 38443950
2024 PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype. International journal of molecular sciences 7 38612413
2025 Combined PARP14 inhibition and PD-1 blockade promotes cytotoxic T cell quiescence and modulates macrophage polarization in relapsed melanoma. Journal for immunotherapy of cancer 6 39870492
2024 A PARP14/TARG1-Regulated RACK1 MARylation Cycle Drives Stress Granule Dynamics in Ovarian Cancer Cells. bioRxiv : the preprint server for biology 6 37873085
2019 PARP-14 Promotes Survival of Mammalian α but Not β Pancreatic Cells Following Cytokine Treatment. Frontiers in endocrinology 6 31130919
2025 PARP14 is an interferon-induced host factor that promotes IFN production and affects the replication of multiple viruses. mBio 5 40937852
2025 Knockdown of YTHDF2 mitigates OGD-induced microglial inflammation by preventing m6A-dependent PARP14 degradation. Journal of neuroimmunology 4 40383033
2025 PARP14 inhibits microglial activation via NNT to alleviate depressive-like behaviors in mice. Brain, behavior, and immunity 3 39978699
2025 Discovery and Optimization of Potent and Highly Selective PARP14 Inhibitors for the Treatment of Atopic Dermatitis. Journal of medicinal chemistry 3 40239060
2025 Targeting PARP14: An in silico framework for identifying novel Competitive inhibitors via 3D-QSAR pharmacophore modeling and molecular dynamics. Computers in biology and medicine 2 40675094
2025 Botulinum toxin A prevents hypertrophic scarring by suppressing PARP14/SOCS2-mediated M2 polarization of macrophages. Biochimica et biophysica acta. Molecular cell research 1 40505894
2025 PARP9-PARP13-PARP14 axis tunes colorectal cancer response to radiotherapy. Journal of experimental & clinical cancer research : CR 1 40646573
2026 The RRM domains of PARP14 mediate replication fork degradation in BRCA2-deficient cells. NAR cancer 0 41684642
2026 Structure, function, regulation, evolution, and therapeutic implications of PARP14. Genes & development 0 41791864
2026 Echinacoside modulates PARP14-GLUD1 axis to mediate energy metabolism reprogramming and mitochondrial function in diminished ovarian reserve. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41895093
2026 Discovery of Highly Potent Phthalazinone Derivatives as PARP14 Inhibitors: From Structure-Based Virtual Screening to In Vivo Pharmacodynamic Activity. Journal of medicinal chemistry 0 42008449
2026 PARP14 as a Master regulator of immune signaling and tumor microenvironment remodeling. Biochemical pharmacology 0 42034313
2025 PARP14-mediated glycolysis enhances Tamoxifen resistance in estrogen receptor + breast cancer cells. Discover oncology 0 40526225
2025 Integrating Transcriptomics and Machine Learning to Uncover the FLI1-PARP14-Immune Axis in Ulcerative Colitis Activity and Pathogenesis. Genes 0 41300794
2025 Investigation of an association between in vitro expression of TMEM154 and PARP14 genes and restriction of SRLV infection in primary skin cells of Carpathian goats. Journal of veterinary research 0 41497468
2024 A multidomain PARP14 construct suitable for bacterial expression. Protein expression and purification 0 39154924
2024 Novel inhibitors of PARP1 and PARP14: design, synthesis, and potentiation of cisplatin efficacy in cancer. Future medicinal chemistry 0 39691063