Affinage

PARP14

Protein mono-ADP-ribosyltransferase PARP14 · UniProt Q460N5

Length
1801 aa
Mass
202.8 kDa
Annotated
2026-06-10
64 papers in source corpus 35 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PARP14 is a large multidomain mono-ADP-ribosyltransferase that operates as a bimodal regulator of cytokine-driven transcription, innate immune signaling, and replication-stress responses (PMID:21081493, PMID:27796300, PMID:36030235). In IL-4 signaling it acts as a transcriptional switch: at baseline it recruits HDAC2/HDAC3 to IL-4-responsive promoters to repress transcription, and upon IL-4 stimulation it ADP-ribosylates these HDACs to release them and permit STAT6-driven gene activation, supporting B-cell survival, glycolysis, and lymphomagenesis (PMID:21081493, PMID:19147789, PMID:21911376). PARP14 catalytic activity also directly ADP-ribosylates STAT1 to suppress STAT1 phosphorylation and pro-inflammatory macrophage activation, an effect antagonized by PARP9 (PMID:27796300). Beyond transcription, PARP14 binds and inhibits the pro-apoptotic kinase JNK1, blocking JNK1-mediated phosphorylation of PKM2 to enforce the Warburg effect and promote tumor-cell survival (PMID:23045269, PMID:26258887). In genome maintenance, PARP14 is recruited to nascent DNA at reversed replication forks via its RRM domains and, through its catalytic activity, drives MRE11 engagement and fork resection, promoting homologous recombination and rendering its loss synthetically lethal with ATR-CHK1 inhibition (PMID:25753673, PMID:36030235, PMID:41684642, PMID:32542389). PARP14 is a major interferon-induced ADP-ribosyltransferase: it auto-MARylates and modifies substrates including PARP13, RACK1, and SQSTM1/p62, and its activity is reversed by its own macrodomain 1—an active de-MARylase (glycohydrolase)—and by the SARS-CoV-2 Nsp3 Mac1 macrodomain (PMID:37703374, PMID:37507011, PMID:30247868, PMID:30848916, PMID:38834853, PMID:38834852). PARP14 nucleates interferon-induced p62-body condensates and restricts replication of several viruses (PMID:40195501, PMID:40937852). PARP14 additionally regulates the stability of select mRNAs, forming a ribonucleoprotein complex with tristetraprolin on tissue factor mRNA (PMID:25293769).

Mechanistic history

Synthesis pass · year-by-year structured walk · 30 steps
  1. 2009 High

    Established that PARP14 is a functional partner of STAT6 controlling cytokine-driven cell fate, linking the protein to IL-4-dependent B-cell survival rather than leaving it an orphan ADP-ribosyltransferase.

    Evidence Parp14-knockout mice, apoptosis and gene expression assays, STAT6 binding assays in primary B cells

    PMID:19147789

    Open questions at the time
    • Did not define whether catalytic activity is required for the STAT6 interaction
    • Molecular mechanism of survival gene induction not resolved
  2. 2010 High

    Answered how PARP14 switches transcription by showing it represses via HDAC recruitment at baseline and de-represses by ADP-ribosylating the HDACs upon IL-4 stimulation, defining a bimodal enzymatic transcriptional switch.

    Evidence ChIP, co-IP, promoter reporter and ADP-ribosylation assays in T/B cells

    PMID:21081493

    Open questions at the time
    • Direct biochemical reconstitution of HDAC ADP-ribosylation not shown
    • Specific modified residues on HDAC2/3 not mapped
  3. 2011 High

    Connected PARP14 to metabolic reprogramming by showing IL-4-induced glycolysis underlies its pro-survival and lymphomagenic function, with AMPK as a rescuing node.

    Evidence Parp14-knockout mice, glycolysis and AMPK activity assays, Myc-driven lymphoma models

    PMID:21911376

    Open questions at the time
    • Direct enzymatic substrate linking PARP14 to glycolytic control not identified
    • Relationship between AMPK rescue and ADP-ribosylation unclear
  4. 2012 High

    Identified a non-transcriptional survival mechanism: PARP14 physically binds and inhibits pro-apoptotic JNK1, placing it downstream of JNK2 in myeloma survival signaling.

    Evidence siRNA/shRNA, overexpression rescue, PARP14-JNK1 co-IP, apoptosis assays in myeloma lines

    PMID:23045269

    Open questions at the time
    • Whether JNK1 is an ADP-ribosylation substrate not established
    • Structural basis of inhibition unknown
  5. 2013 High

    Defined PARP14 macrodomains 2 and 3 as readers of mono-ADP-ribose with substrate selectivity, establishing PARP14 as both writer and reader of MARylation.

    Evidence Crystal structures, ITC, binding/co-localization assays with MARylated ARTD10 and Ran

    PMID:23473667

    Open questions at the time
    • In vivo MARylated ligands recognized by these macrodomains not defined
    • Functional consequence of reading in cells not tested
  6. 2013 High

    Showed PARP14 catalytic activity shapes adaptive immunity, driving Th17 differentiation and IL-4-dependent IgE/IgA responses through transcription-factor expression.

    Evidence Parp14-deficient and catalytic-mutant mice, antibody isotype and flow-cytometric analyses

    PMID:23956424

    Open questions at the time
    • Direct substrates mediating RORα/Runx1/Smad3 induction unknown
    • B-cell-intrinsic vs extrinsic mechanisms incompletely separated
  7. 2015 High

    Linked the JNK1-inhibitory function to metabolism by defining the PARP14-JNK1-PKM2 axis controlling aerobic glycolysis in hepatocellular carcinoma.

    Evidence In vitro/in vivo loss-of-function, PKM2 Thr365 phosphorylation and glycolysis assays

    PMID:26258887

    Open questions at the time
    • Catalytic requirement of PARP14 for JNK1 inhibition not resolved
  8. 2015 High

    Placed PARP14 in genome maintenance by demonstrating its PCNA interaction and requirement for homologous recombination and replication of difficult loci.

    Evidence PARP14-PCNA co-IP, siRNA, RAD51 foci, HR reporter and comet assays

    PMID:25753673

    Open questions at the time
    • Domain mediating PCNA interaction not mapped here
    • Whether catalytic activity is required not yet tested
  9. 2016 High

    Identified STAT1 as a direct ADP-ribosylation substrate whose modification suppresses phosphorylation, defining the PARP14/PARP9 cross-regulatory axis of macrophage activation.

    Evidence Proteomics, STAT1 site mutagenesis, PARP14/PARP9 silencing in primary macrophages

    PMID:27796300

    Open questions at the time
    • Structural basis of STAT1 ADP-ribose-mediated phospho-suppression unknown
  10. 2014 High

    Demonstrated a post-transcriptional role: PARP14 forms an RNP with tristetraprolin to control tissue factor mRNA stability with transcript selectivity.

    Evidence RNP-IP, biotinylated RNA pulldown, knockout macrophages, mRNA stability and coagulation assays

    PMID:25293769

    Open questions at the time
    • Whether ADP-ribosylation drives the mRNA stabilization not established
    • Basis of transcript selectivity unknown
  11. 2014 Medium

    Defined a stable PARP14-PARP9-DTX3L complex required for cancer-cell survival, establishing physical assembly of these ADP-ribosylation machinery components.

    Evidence Reciprocal co-IP, immunofluorescence, siRNA, catalytic-mutant survival assays in prostate cancer cells

    PMID:24886089

    Open questions at the time
    • Single-lab study
    • Stoichiometry and architecture of the complex not resolved
  12. 2017 High

    Provided structural and enzymatic characterization of PARP14 auto-ADP-ribosylation and NAD+-competitive inhibition, enabling pharmacological targeting.

    Evidence Purified protein, RapidFire MS and [3H]NAD+ auto-ribosylation assays, co-crystal structures with inhibitors

    PMID:28315326

    Open questions at the time
    • Physiological consequences of auto-modification not addressed here
  13. 2018 High

    Showed PARP14 translocates to the nucleus on inflammatory stimulation, binds ISG-encoded proteins, and is required for IRF3-dependent antiviral transcription including IFN-β.

    Evidence Fractionation, quantitative MS interactome, siRNA, RT-qPCR, Salmonella infection assays

    PMID:29500242

    Open questions at the time
    • Whether catalytic activity drives ISG-protein nuclear accumulation not resolved
  14. 2018 High

    Defined the PARP14-specific MARylation substrate landscape via chemical genetics and proximity labeling, revealing enrichment for RNA-regulatory proteins and identifying PARP13 as a direct substrate.

    Evidence Orthogonal NAD+ analog with engineered PARP14, BioID, MS substrate ID, in vitro validation

    PMID:30247868

    Open questions at the time
    • Functional consequences of most identified substrates untested
    • Modified residues on most substrates not mapped
  15. 2019 Medium

    Provided first direct mapping of IFNγ-induced ADP-ribosylation on PARP14 and PARP9 in macrophages, establishing these PARPs as auto/cross-modification targets in interferon signaling.

    Evidence Af1521 enrichment, EThcD/HCD MS/MS of IFNγ-treated THP-1 macrophages

    PMID:30848916

    Open questions at the time
    • No mutagenesis validation of specific sites
    • Functional role of identified sites untested
  16. 2020 High

    Revealed PARP14 as a critical co-factor of MRE11 at reversed forks in BRCA-deficient cells, defining a KU-PARP14-MRE11-EXO1 resection pathway dependent on catalytic activity.

    Evidence iPOND, PLA, DNA fiber and S1 nuclease assays, MRE11/KU co-IP, PARP14 inhibition/knockout

    PMID:36030235

    Open questions at the time
    • Direct ADP-ribosylation substrate enabling MRE11 engagement not identified
  17. 2020 Medium

    Identified ATR-CHK1 as synthetically lethal with PARP14 loss, mechanistically tying PARP14 to replication-dynamics control and nominating a therapeutic vulnerability.

    Evidence Genome-wide CRISPR knockout screen, ATR/CHK1 inhibitor treatment, DNA fiber assays

    PMID:32542389

    Open questions at the time
    • Single lab
    • Molecular mechanism linking PARP14 to ATR-CHK1 dependence incompletely defined
  18. 2020 Medium

    Extended PARP14 function to CNS injury, showing it limits microglial activation and promotes post-stroke recovery via suppression of LPAR5 transcription.

    Evidence Photothrombotic stroke model with PARP14 knockdown/overexpression, pharmacological inhibition, LPAR5 promoter analysis

    PMID:33317392

    Open questions at the time
    • Single lab
    • Direct link between ADP-ribosylation and LPAR5 transcription unresolved
  19. 2021 Medium

    Showed PARP14 controls cyclin D1 expression via 3'UTR mRNA stability, governing G1 progression through the RB and p53-p21 pathways.

    Evidence siRNA depletion, luciferase 3'UTR reporters, cell-cycle and western analyses

    PMID:34158578

    Open questions at the time
    • Single lab
    • Whether ADP-ribosylation mediates the 3'UTR effect not shown
  20. 2022 Medium

    Connected PARP14 transcriptional regulation to EP4 receptor expression in colon cancer through MARylation of HDAC1/HDAC2.

    Evidence siRNA, PARP14 inhibitor, RT-qPCR, western, HDAC ADP-ribosylation assays

    PMID:35914351

    Open questions at the time
    • No direct biochemical reconstitution of HDAC1/2 modification
    • Single lab
  21. 2022 Medium

    Implicated PARP14 in AML glycolysis through an NF-κB/HIF-1α axis, extending its metabolic role to myeloid leukemia.

    Evidence siRNA/overexpression, NF-κB inhibitor, HIF-1α siRNA rescue, glycolysis assays, xenografts

    PMID:35944879

    Open questions at the time
    • Single lab
    • Mechanism by which PARP14 activates NF-κB not defined
  22. 2023 High

    Reclassified PARP14 as a dual-function enzyme by demonstrating its macrodomain 1 is an active de-MARylase, with viral Nsp3 Mac1 reversing PARP14 modifications.

    Evidence In vitro reconstitution, macrodomain-1 mutagenesis, cellular MARylation detection, SARS-CoV-2 Mac1 reversal

    PMID:37703374

    Open questions at the time
    • Physiological balance between writer and eraser activities not quantified
  23. 2023 High

    Characterized PARP14 (and PARP9) macrodomain-1 as ADP-ribosyl glycohydrolases not directed to specific side chains and inactive on poly(ADP-ribose), revealing mechanistic homology to SARS-CoV-2 Mac1.

    Evidence In vitro hydrolysis assays, F926A/F244A mutagenesis, PARP1 poly-ADP-ribose comparison

    PMID:37507011

    Open questions at the time
    • Single lab
    • Endogenous substrates of the glycohydrolase activity not defined
  24. 2024 High

    Showed IFNγ-induced cellular ADP-ribosylation depends on PARP14 catalysis and that PARP9/DTX3L post-translationally control PARP14 levels and co-localize at cytoplasmic ADPr inclusions.

    Evidence IFNγ treatment with anti-mono-ADPr detection, catalytic mutant, PARP9/DTX3L siRNA, immunofluorescence, Nsp3 Mac1 reversal (two convergent papers)

    PMID:38834852 PMID:38834853

    Open questions at the time
    • Mechanism of post-translational PARP14 level control by PARP9/DTX3L not detailed
  25. 2024 Medium

    Defined KH-like domains as the structural basis for PARP14-DTX3L-PARP9 interactions, with DTX3L binding suppressing PARP14 auto-modification and redirecting it to trans-modification.

    Evidence Co-IP, KH-domain mutagenesis, PARP14 truncation rescue, in vitro ADP-ribosylation assays

    PMID:38182103

    Open questions at the time
    • Single lab
    • Cellular consequence of DTX3L-redirected activity not established
  26. 2024 Medium

    Identified RACK1 as a PARP14 MARylation substrate whose modification drives stress-granule formation and selective translational repression, reversed by TARG1.

    Evidence MS site mapping, RACK1 mutagenesis, stress-granule imaging, polysome profiling, xenograft (preprint)

    PMID:37873085

    Open questions at the time
    • Preprint, not peer-reviewed
    • Generality beyond ovarian cancer cells untested
  27. 2025 Medium

    Showed PARP14 catalytic activity enhances IFN-β/IFN-γ responses and restricts ARH-deficient coronaviruses and HSV-1 while being pro-viral for VSV, separating catalytic from non-catalytic antiviral roles.

    Evidence CRISPR-knockout A549 cells, multi-virus replication assays, active-site inhibitor, IFN ELISA

    PMID:40937852

    Open questions at the time
    • Single lab
    • Catalytic substrates underlying virus restriction not identified
  28. 2025 High

    Demonstrated that PARP14 both physically scaffolds and catalytically maintains interferon-induced p62-body condensates containing selective autophagy receptors and polyubiquitin but lacking LC3B.

    Evidence PARP14/p62 siRNA, catalytic mutant, immunofluorescence, autophagy/proteasome/ubiquitination inhibitors

    PMID:40195501

    Open questions at the time
    • Functional output of these condensates incompletely defined
    • p62 cysteine-MARylation role within condensates not fully linked
  29. 2026 High

    Identified PARP14 RRM domains as the recruitment module to reversed forks required for MRE11 engagement and nascent-strand degradation in BRCA2-deficient cells, refining the structural basis of its replication-stress role.

    Evidence iPOND, domain truncation/deletion constructs, DNA fiber, γH2AX and MRE11 foci assays

    PMID:41684642

    Open questions at the time
    • RNA ligand, if any, bound by the RRMs at forks unknown
    • Single lab
  30. 2026 Medium

    Extended PARP14 substrate repertoire to metabolic enzyme GLUD1, whose MARylation inhibits glutamate dehydrogenase activity and suppresses mitochondrial energy metabolism.

    Evidence Co-IP, in vitro ADP-ribosylation, GLUD1 activity and α-KG measurements in granulosa cells

    PMID:41895093

    Open questions at the time
    • Single lab
    • Modified residues on GLUD1 not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which direct ADP-ribosylation substrates mediate PARP14's transcriptional, replication-fork, and antiviral phenotypes, and how the balance between its transferase and macrodomain-1 hydrolase activities is regulated in vivo.
  • Causal substrate-to-phenotype links largely inferential
  • In vivo regulation of writer/eraser balance unquantified
  • Structural basis of many substrate interactions undetermined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0003723 RNA binding 3 GO:0016740 transferase activity 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0016787 hydrolase activity 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005829 cytosol 3
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-168256 Immune System 4 R-HSA-73894 DNA Repair 4 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 3
Partners
DTX3LJNK1MRE11PARP13PARP9PCNASTAT1STAT6
Complex memberships
PARP14-PARP9-DTX3L complexPARP14-tristetraprolin (TTP) ribonucleoprotein complexp62-body condensate

Evidence

Reading pass · 34 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, PARP-14 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, promoting STAT6 binding to target promoters, and enabling coactivator with HAT activity to replace the repressor complex. Chromatin immunoprecipitation, co-immunoprecipitation, promoter reporter assays, ADP-ribosylation assays in T cells/B cells The Journal of biological chemistry High 21081493
2013 PARP14 (ARTD8) macrodomains 2 and 3 act as readers of mono-ADP-ribosylation: crystal structures and isothermal titration calorimetry confirmed their interaction with ADP-ribose, and they specifically recognized mono-ADP-ribosylated ARTD10 and its substrate Ran, but not poly-ADP-ribosylated ARTD1, distinguishing them from the macroH2A1.1 macrodomain. Crystal structure determination, isothermal titration calorimetry, co-localization and binding assays in vitro and in cells Structure (London, England : 1993) High 23473667
2009 PARP-14 mediates IL-4-dependent survival signaling in primary B cells: PARP-14-deficient mice show increased apoptosis in IL-4-treated B cells including after DNA damage, and PARP-14 regulates IL-4-induced expression of gene products controlling survival, proliferation, and lymphomagenesis. PARP-14 physically interacts with the IL-4-induced transcription factor STAT6. Knockout mouse studies, apoptosis assays, gene expression analysis, binding assays Blood High 19147789
2011 PARP14 is required for IL-4-induced enhancement of glycolysis in B cells, and this glycolytic activity mediates IL-4-dependent pro-survival signaling. PARP14 deficiency delayed B lymphomagenesis and reversed the block to B-cell maturation driven by the Myc oncogene; restoration of AMP-activated protein kinase activity rescued glycolytic activity and prosurvival signaling in Parp14-deficient B cells. Parp14 knockout mice, glycolysis assays, AMPK activity assays, lymphoma mouse models, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 21911376
2012 PARP14 is a downstream effector of JNK2-dependent pro-survival signaling in multiple myeloma: JNK2 constitutive activation maintains PARP14 expression; PARP14 promotes myeloma cell survival by physically binding and inhibiting the pro-apoptotic kinase JNK1; overexpression of PARP14 completely rescued myeloma cells from apoptosis induced by JNK2 knockdown. Loss-of-function (siRNA/shRNA) studies, overexpression rescue experiments, co-immunoprecipitation (PARP14-JNK1 interaction), apoptosis assays Oncogene High 23045269
2015 PARP14 promotes the Warburg effect in hepatocellular carcinoma by inhibiting JNK1: PARP14 suppresses JNK1 kinase activity, which prevents JNK1-mediated phosphorylation of PKM2 at Thr365 that would otherwise activate PKM2 and reduce aerobic glycolysis. This PARP14-JNK1-PKM2 axis links anti-apoptotic signaling to metabolic reprogramming. Loss-of-function studies (siRNA/shRNA) in vitro and in vivo (xenograft), PKM2 phosphorylation assays, glycolysis measurements, apoptosis assays Nature communications High 26258887
2015 PARP14 promotes homologous recombination DNA repair and protects against replication stress: PARP14 interacts with PCNA and promotes replication of DNA lesions and common fragile sites; PARP14 depletion results in reduced homologous recombination, persistent RAD51 foci, hypersensitivity to DNA damaging agents, and accumulation of DNA strand breaks. Co-immunoprecipitation (PARP14-PCNA), siRNA knockdown, RAD51 foci assays, HR reporter assays, comet assays, sensitivity assays Nucleic acids research High 25753673
2016 PARP14 induces ADP-ribosylation of STAT1, which suppresses STAT1 phosphorylation; PARP9 antagonizes this by suppressing PARP14-mediated ADP-ribosylation of STAT1. Mutations at the PARP14-dependent ADP-ribosylation sites on STAT1 lead to increased STAT1 phosphorylation. PARP14 and PARP9 thus cross-regulate macrophage activation via opposing effects on STAT1 activity. Global proteomic analysis, ADP-ribosylation assays, site-directed mutagenesis of STAT1, PARP14/PARP9 silencing in primary macrophages, phosphorylation assays Nature communications High 27796300
2014 PARP-14 selectively regulates macrophage tissue factor (TF) mRNA stability by forming a ribonucleoprotein complex with the mRNA-destabilizing protein tristetraprolin (TTP) and a conserved AU-rich element in the TF mRNA 3' UTR; PARP-14 deficiency leads to increased TF mRNA stability, TF expression, and TF activity in macrophages, while TNFα mRNA (also regulated by TTP) is unaffected. Ribonucleoprotein immunoprecipitation, biotinylated RNA pulldown, PARP14-knockout macrophages (in vitro and in vivo), mRNA stability assays, TF functional coagulation assays Blood High 25293769
2018 PARP14 translocates into the nucleus of macrophages upon inflammatory stimulation, binds a group of IFN-stimulated gene (ISG)-encoded proteins by quantitative mass spectrometry, and is required for their nuclear accumulation. PARP14 depletion attenuates IFN regulatory factor 3-dependent antiviral gene transcription including Ifnb1, reducing IFN-β production. Nuclear/cytoplasmic fractionation, quantitative mass spectrometry for interactors, siRNA knockdown, RT-qPCR, Salmonella infection assays Journal of immunology (Baltimore, Md. : 1950) High 29500242
2018 Using a chemical genetics approach (orthogonal NAD+ analog with engineered PARP14 variant) combined with BioID proximity-dependent labeling, 114 PARP14-specific MARylation substrates were identified, enriched for RNA regulatory proteins. PARP13 was identified as a direct PARP14 MARylation substrate, modified on several acidic amino acids. Chemical genetics (orthogonal NAD+ analog), BioID proximity labeling, mass spectrometry substrate identification, in vitro ADP-ribosylation assays ACS chemical biology High 30247868
2013 PARP14 catalytic activity promotes Th17 cell differentiation and is required for IL-4-dependent IgE antibody responses (B cell-intrinsic) and IgA antibody responses (predominantly B cell-extrinsic involving Th17 cells and CD103+ dendritic cells). PARP14 enhances expression of RORα, Runx1, and Smad3 after T cell activation. PARP14-deficient mice, antibody isotype measurements, flow cytometric analysis of Th17 cells and DC populations, gene expression analysis, catalytic mutant studies Journal of immunology (Baltimore, Md. : 1950) High 23956424
2017 PARP14 catalyzes auto-ADP-ribosylation (auto-ribosylation), and co-crystal structures of PARP14 with inhibitor compounds showed that small-molecule inhibitors bind to the NAD+-binding site of the catalytic domain, acting as NAD+-competitive inhibitors. Purified PARP14 protein, RapidFire high-throughput mass spectrometry auto-ribosylation assay, [3H]NAD+ immunoradiometric assay, co-crystal structure determination, cell-based protein stabilization assay Biochemical and biophysical research communications High 28315326
2023 PARP14 is a dual-function enzyme with both mono-ADP-ribosyl transferase and ADP-ribosyl hydrolase activities: the macrodomain 1 of PARP14 acts as an active ADP-ribosyl hydrolase (de-MARylase). Inactivation of macrodomain 1 (hydrolase-dead mutant) results in marked increase of protein mono-ADP-ribosylation in human cells, including auto-MARylation of PARP14 and MARylation of antiviral PARP13. The SARS-CoV-2 Nsp3 Mac1 macrodomain efficiently reverses PARP14 ADP-ribosylation in vitro and in cells. In vitro ADP-ribosylation and hydrolysis assays, macrodomain 1 mutagenesis, cellular MARylation detection with improved antibodies, SARS-CoV-2 Mac1 reversal assays 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; this activity does not degrade poly(ADP-ribose). The F926A mutation of PARP14 and F244A of PARP9 strongly reduced glycohydrolase activity, revealing mechanistic homology to the SARS-CoV-2 Nsp3 Mac1 domain. Biochemical ADP-ribosylation hydrolysis assays, site-directed mutagenesis (F926A PARP14, F244A PARP9), comparison with PARP1 poly-ADP-ribose substrate The Journal of biological chemistry High 37507011
2020 PARP14 is a critical co-factor of MRE11 at reversed 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. The KU complex binds reversed forks and recruits the PARP14-MRE11 complex, which initiates partial resection to release KU and allow long-range resection by EXO1. Loss or inhibition of PARP14 suppresses MRE11-mediated fork degradation and ssDNA gap accumulation. iPOND (isolation of proteins on nascent DNA), proximity ligation assays, PARP14 inhibition/knockout, DNA fiber assays, S1 nuclease gap assays, MRE11 co-immunoprecipitation, KU interaction assays Nature communications High 36030235
2024 IFNγ-induced ADP-ribosylation in cells depends on PARP14 catalytic activity; the PARP9/DTX3L complex regulates PARP14 protein levels via post-translational mechanisms (not transcriptional) and both localize to IFNγ-induced cytoplasmic inclusions containing ADP-ribosylated proteins. PARP14 itself and DTX3L are ADP-ribosylation targets; the SARS-CoV-2 Nsp3 macrodomain reverses these modifications. IFNγ treatment with mono-ADPr antibody detection, PARP14 catalytic mutant, siRNA knockdown of PARP9/DTX3L, immunofluorescence, western blot for protein levels, Nsp3 Mac1 reversal The EMBO journal High 38834852 38834853
2021 PARP14 regulates cyclin D1 expression at the mRNA level via cyclin D1 3'UTR stability: depletion of PARP14 decreases cyclin D1 protein levels, leading to G1 cell-cycle arrest in cells with functional RB pathway, dependent on an intact p53-p21 pathway. PARP14 siRNA depletion, luciferase 3'UTR reporter assays, cell cycle analysis (flow cytometry), western blot for cyclin D1/RB/p53 pathway components Oncogene Medium 34158578
2020 Genome-wide CRISPR knockout screen in PARP14-deficient cells identified the ATR-CHK1 pathway as synthetically lethal with PARP14 loss, and mechanistically linked this to regulation of DNA replication dynamics; inhibition of the ATR-CHK1 pathway in PARP14-deficient cells leads to cell death through replication stress. Genome-wide CRISPR knockout genetic screen, ATR/CHK1 inhibitor treatment of PARP14-deficient cells, DNA fiber assays Nucleic acids research Medium 32542389
2014 DTX3L (BBAP) forms a protein complex with PARP14 (ARTD8) and PARP9 (ARTD9) in metastatic prostate cancer cells; the enzymatic activity of PARP14 is required for survival of these cells, and the complex mediates proliferation, chemo-resistance, and survival. Co-immunoprecipitation, immunofluorescence, siRNA knockdown, cell proliferation/survival assays, catalytic mutant analysis Molecular cancer Medium 24886089
2022 PARP14 regulates EP4 receptor expression in colon cancer cells through mono-ADP-ribosylation of HDAC1 and HDAC2; suppression of PARP14 activity by siRNA or inhibitors reduced EP4 receptor mRNA and protein expression. siRNA knockdown, PARP14 inhibitor treatment, RT-qPCR, western blot, HDAC ADP-ribosylation assays Biochemical and biophysical research communications Medium 35914351
2024 KH-like domains in PARP14 and PARP9/DTX3L coordinate protein-protein interactions important to pro-survival signaling: KH-like domains mediate PARP9-DTX3L and PARP14-DTX3L interactions; homodimerization of DTX3L is also coordinated by a KH-like domain. In vitro, DTX3L interaction with PARP14 suppresses PARP14 auto-ADP-ribosylation and promotes trans-ADP-ribosylation of PARP9 and DTX3L. Co-immunoprecipitation, site-directed mutagenesis of KH domain, PARP14 truncation rescue experiments, in vitro ADP-ribosylation assays Journal of molecular biology Medium 38182103
2024 PARP14 mono-ADP-ribosylates RACK1 (an integral ribosome component) on three acidic residues in ovarian cancer cells; MARylation of RACK1 is required for stress granule formation and promotes colocalization of RACK1 with G3BP1, eIF3η, and 40S ribosomal subunits in stress granules, while reducing translation of a subset of mRNAs including AKT. The ADP-ribosyl hydrolase TARG1 reverses this modification, allowing stress granule dissociation and translation restoration. Mass spectrometry identification of MARylation sites, PARP14 inhibitor, site-directed mutagenesis of RACK1 MARylation sites, stress granule imaging, polysome profiling, in vivo tumor xenograft bioRxivpreprint Medium 37873085
2025 PARP14 catalytic activity enhances IFN-β and IFN-γ responses and restricts replication of ARH-deficient coronaviruses (MHV, SARS-CoV-2) and HSV-1. PARP14 has pro-viral function for VSV, as its knockout decreased VSV replication. The effects on HSV-1 and VSV were independent of PARP14 catalytic activity as demonstrated by an active site inhibitor having no effect. PARP14 knockout (CRISPR) A549 cells, viral replication assays for MHV, SARS-CoV-2, HSV-1, VSV, LCMV; PARP14 active site inhibitor treatment; IFN-β/IFN-γ ELISA mBio Medium 40937852
2025 Interferon induces PARP14-mediated mono-ADP-ribosylation of SQSTM1/p62 at cysteine residues 113, 289/290, and 331; this creates cytoplasmic p62 foci colocalizing with ubiquitin and PARP14 but lacking LC3, distinguishing them from autophagosomes. TRIM21 prevents autophagic degradation of ADP-ribosylated p62. The SARS-CoV-2 macrodomain reverses this p62 modification. Mass spectrometry for site identification, site-directed mutagenesis of p62 cysteines, immunofluorescence, PARP14 catalytic inhibition, SARS-CoV-2 macrodomain reversal assays, TRIM21 knockdown bioRxivpreprint Medium bio_10.1101_2024.06.29.601315
2025 Interferon-induced PARP14-mediated ADP-ribosylation occurs within p62 body condensates: PARP14 physical presence and catalytic activity are both required for condensate formation. These PARP14/ADPr condensates contain p62, NBR1, TAX1BP1, and K48/K63-linked polyubiquitin but lack LC3B; p62 knockdown disrupts condensate formation. Condensate integrity is independent of autophagy but requires ubiquitination and proteasome activity. siRNA knockdown of PARP14 and p62, PARP14 catalytic mutant expression, immunofluorescence, autophagy inhibitors (bafilomycin), proteasome inhibitors, ubiquitination inhibitors The EMBO journal High 40195501
2026 PARP14 is recruited to nascent DNA at reversed replication forks in BRCA2-deficient cells via its RRM (RNA Recognition Motif) domains; these domains are necessary for MRE11 recruitment to reversed forks, for promotion of nascent strand degradation, and for replication stress-induced double-strand break formation in BRCA2-deficient cells. iPOND, PARP14 domain truncation/deletion constructs, DNA fiber assays, DSB (γH2AX) analysis, MRE11 foci assays in BRCA2-deficient cells NAR cancer High 41684642
2026 PARP14 mediates MARylation of GLUD1 (glutamate dehydrogenase 1), inhibiting GLUD1 enzyme activity via mono-ADP-ribosylation, which reduces alpha-ketoglutarate production and suppresses mitochondrial energy metabolism in granulosa cells. Co-immunoprecipitation, in vitro ADP-ribosylation assay, GLUD1 enzyme activity measurement, metabolite (α-KG) quantification, PARP14 overexpression/knockdown Phytomedicine Medium 41895093
2020 PARP14 promotes post-stroke functional recovery by inhibiting microglial activation through suppression of LPAR5 (lysophosphatidic acid receptor 5) gene transcription; PARP14 overexpression in microglia attenuates post-stroke microglial activation possibly through modulation of macroautophagy. PARP14 genetic knockdown/overexpression in photothrombotic stroke mouse model, pharmacological PARP14 inhibition, microglial activation assays, LPAR5 promoter analysis, autophagy modulation assays Autophagy Medium 33317392
2019 PARP14 ADP-ribosylates itself (auto-ribosylation); mass spectrometry detected IFNγ-induced ADP-ribosylation of PARP14 (ARTD8) along with PARP9 (ARTD9) in macrophages, providing first characterization of ADP-ribosylation on these PARP family members. Af1521 enrichment of ADP-ribosylated peptides, anti-poly-ADPr antibody enrichment, EThcD and HCD MS/MS, IFNγ treatment of THP-1 macrophages Journal of proteome research Medium 30848916
2022 PARP14 promotes AML cell glycolysis by activating NF-κB signaling, which in turn promotes HIF-1α expression; HIF-1α silencing reverses the cancer-promoting effects of PARP14 overexpression. siRNA/overexpression of PARP14, NF-κB inhibitor (BAY11-7082), HIF-1α siRNA rescue, glycolysis assays (ECAR, glucose consumption, lactate production), xenograft tumor model Clinical immunology Medium 35944879
2025 PARP14 inhibits microglial activation and depressive-like behavior by positively regulating nicotinamide nucleotide transhydrogenase (NNT) expression in microglia; NNT deficiency leads to ROS accumulation and microglial inflammation, which PARP14 suppresses via NNT-mediated ROS clearance. CUS mouse model, hippocampal PARP14 knockdown/overexpression, microglial-targeted AAV overexpression, NNT overexpression rescue, ROS inhibitor (NAC) treatment, microglial activation assays Brain, behavior, and immunity Medium 39978699
2025 YTHDF2 (m6A reader) interacts with PARP14 mRNA under oxygen-glucose deprivation (OGD) conditions, promoting m6A-dependent degradation of PARP14 mRNA and reducing PARP14 protein levels; this mechanism enables YTHDF2-dependent suppression of PARP14-driven M2 microglial polarization. RIP (RNA immunoprecipitation) for YTHDF2-PARP14 mRNA interaction, siRNA knockdown of YTHDF2, mRNA stability assays, microglial phenotype assays Journal of neuroimmunology Medium 40383033
2025 PARP14 enhances SOCS2 mRNA stability, promoting M2 macrophage polarization relevant to hypertrophic scarring; overexpression of PARP14 restored M2 polarization in macrophages treated with botulinum toxin A, which was counteracted by additional SOCS2 silencing. RNA sequencing, PARP14 overexpression, SOCS2 silencing rescue experiments, mRNA stability assays, in vivo mouse HS model, THP-1 M2 polarization model Biochimica et biophysica acta. Molecular cell research Medium 40505894

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 238 27796300
2015 PARP14 promotes the Warburg effect in hepatocellular carcinoma by inhibiting JNK1-dependent PKM2 phosphorylation and activation. Nature communications 190 26258887
2010 PARP-14 functions as a transcriptional switch for Stat6-dependent gene activation. The Journal of biological chemistry 123 21081493
2013 Recognition of mono-ADP-ribosylated ARTD10 substrates by ARTD8 macrodomains. Structure (London, England : 1993) 111 23473667
2014 DTX3L and ARTD9 inhibit IRF1 expression and mediate in cooperation with ARTD8 survival and proliferation of metastatic prostate cancer cells. Molecular cancer 97 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 95 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 93 21911376
2009 PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells. Blood 85 19147789
2018 PARP14 Controls the Nuclear Accumulation of a Subset of Type I IFN-Inducible Proteins. Journal of immunology (Baltimore, Md. : 1950) 77 29500242
2020 PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery. Autophagy 63 33317392
2023 PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities. Science advances 62 37703374
2014 PARP-14 combines with tristetraprolin in the selective posttranscriptional control of macrophage tissue factor expression. Blood 62 25293769
2015 Identification of a novel PARP14-TFE3 gene fusion from 10-year-old FFPE tissue by RNA-seq. Genes, chromosomes & cancer 57 26032162
2018 Combining Chemical Genetics with Proximity-Dependent Labeling Reveals Cellular Targets of Poly(ADP-ribose) Polymerase 14 (PARP14). ACS chemical biology 55 30247868
2015 A novel role for the mono-ADP-ribosyltransferase PARP14/ARTD8 in promoting homologous recombination and protecting against replication stress. Nucleic acids research 53 25753673
2021 PARP14 regulates cyclin D1 expression to promote cell-cycle progression. Oncogene 46 34158578
2024 PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation. The EMBO journal 43 38834853
2019 Research Progress on PARP14 as a Drug Target. Frontiers in pharmacology 42 30890936
2022 The KU-PARP14 axis differentially regulates DNA resection at stalled replication forks by MRE11 and EXO1. Nature communications 41 36030235
2013 B cell-intrinsic and -extrinsic regulation of antibody responses by PARP14, an intracellular (ADP-ribosyl)transferase. Journal of immunology (Baltimore, Md. : 1950) 32 23956424
2023 PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models. Nature communications 31 37752135
2022 PARP14 promotes the growth and glycolysis of acute myeloid leukemia cells by regulating HIF-1α expression. Clinical immunology (Orlando, Fla.) 31 35944879
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
2019 PARP14 promotes the proliferation and gemcitabine chemoresistance of pancreatic cancer cells through activation of NF-κB pathway. Molecular carcinogenesis 30 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 29 32542389
2024 PARP14 is regulated by the PARP9/DTX3L complex and promotes interferon γ-induced ADP-ribosylation. The EMBO journal 28 38834852
2023 PARP14 is a writer, reader, and eraser of mono-ADP-ribosylation. The Journal of biological chemistry 28 37507011
2024 KH-like Domains in PARP9/DTX3L and PARP14 Coordinate Protein-Protein Interactions to Promote Cancer Cell Survival. Journal of molecular biology 27 38182103
2017 Identification of PARP14 inhibitors using novel methods for detecting auto-ribosylation. Biochemical and biophysical research communications 26 28315326
2023 Mono-ADP-ribosylation by PARP10 and PARP14 in genome stability. NAR cancer 25 36814782
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
2018 Discovery of a novel allosteric inhibitor scaffold for polyadenosine-diphosphate-ribose polymerase 14 (PARP14) macrodomain 2. Bioorganic & medicinal chemistry 23 29567296
2018 Structure, Function and Inhibition of Poly(ADP-ribose)polymerase, Member 14 (PARP14). Mini reviews in medicinal chemistry 23 30112992
2022 PARP14 is a novel target in STAT6 mutant follicular lymphoma. Leukemia 22 35851155
2023 FHL2 regulates microglia M1/M2 polarization after spinal cord injury via PARP14-depended STAT1/6 pathway. International immunopharmacology 18 37708708
2021 Targeted Degradation of PARP14 Using a Heterobifunctional Small Molecule. Chembiochem : a European journal of chemical biology 18 33838082
2024 Targeting PARP14 with lomitapide suppresses drug resistance through the activation of DRP1-induced mitophagy in multiple myeloma. Cancer letters 14 38467180
2025 Interferon-induced PARP14-mediated ADP-ribosylation in p62 bodies requires the ubiquitin-proteasome system. The EMBO journal 12 40195501
2024 Pterosin B improves cognitive dysfunction by promoting microglia M1/M2 polarization through inhibiting Klf5/Parp14 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 12 39413455
2022 PARP14 regulates EP4 receptor expression in human colon cancer HCA-7 cells. Biochemical and biophysical research communications 11 35914351
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
2022 Selective Pharmaceutical Inhibition of PARP14 Mitigates Allergen-Induced IgE and Mucus Overproduction in a Mouse Model of Pulmonary Allergic Response. ImmunoHorizons 10 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 9 38443950
2024 PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype. International journal of molecular sciences 8 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 7 39870492
2025 Discovery and Optimization of Potent and Highly Selective PARP14 Inhibitors for the Treatment of Atopic Dermatitis. Journal of medicinal chemistry 6 40239060
2025 PARP14 is an interferon-induced host factor that promotes IFN production and affects the replication of multiple viruses. mBio 6 40937852
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 Knockdown of YTHDF2 mitigates OGD-induced microglial inflammation by preventing m6A-dependent PARP14 degradation. Journal of neuroimmunology 5 40383033
2025 PARP14 inhibits microglial activation via NNT to alleviate depressive-like behaviors in mice. Brain, behavior, and immunity 4 39978699
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 4 40675094
2025 Botulinum toxin A prevents hypertrophic scarring by suppressing PARP14/SOCS2-mediated M2 polarization of macrophages. Biochimica et biophysica acta. Molecular cell research 3 40505894
2025 PARP9-PARP13-PARP14 axis tunes colorectal cancer response to radiotherapy. Journal of experimental & clinical cancer research : CR 2 40646573
2026 The RRM domains of PARP14 mediate replication fork degradation in BRCA2-deficient cells. NAR cancer 1 41684642
2025 PARP14-mediated glycolysis enhances Tamoxifen resistance in estrogen receptor + breast cancer cells. Discover oncology 1 40526225
2024 Novel inhibitors of PARP1 and PARP14: design, synthesis, and potentiation of cisplatin efficacy in cancer. Future medicinal chemistry 1 39691063
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 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

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