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Showing TIPARP — PARP-1 is a alias.

TIPARP

Protein mono-ADP-ribosyltransferase TIPARP · UniProt Q7Z3E1

Length
657 aa
Mass
76.2 kDa
Annotated
2026-06-10
70 papers in source corpus 32 papers cited in narrative 32 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

TIPARP (PARP7/ARTD14) is a nuclear mono-ADP-ribosyltransferase that acts as a negative-feedback regulator of inducible transcription factors by MARylating them, predominantly on cysteine residues, to control their activity and stability (PMID:23275542, PMID:33475084). Its founding role is in aryl hydrocarbon receptor (AHR) signaling: TIPARP is induced by AHR, MARylates AHR to drive its nuclear export and proteasomal degradation, and thereby dampens dioxin-responsive CYP1A1/CYP1B1 transcription; this repression requires both the zinc-finger and catalytic domains and the catalytic residue H532 in vivo (PMID:23275542, PMID:25975270, PMID:34146543, PMID:34129049). The same writer/eraser logic extends across targets—MACROD1 reverses TIPARP-placed ADP-ribose marks on AHR (PMID:25975270)—and TIPARP similarly MARylates and regulates HIF-1α, c-Myc, ERα, the androgen receptor, FRA1, and LXRα/β, in several cases nucleating ADP-ribosylation-dependent nuclear bodies that recruit E3 ligases to trigger degradation (PMID:26814197, PMID:32482854, PMID:33799807, PMID:34264286, PMID:38011562, PMID:40681873). TIPARP-generated ADP-ribosyl marks are recognized as degrons by E3 ligases including HUWE1 and DTX2, and DTX2 also degrades auto-MARylated PARP7 itself, establishing mono-ADP-ribosylation as a bona fide degradation signal (PMID:32482854, PMID:40681873, PMID:41326691). Beyond transcription factors, TIPARP MARylates α-tubulin to promote microtubule instability, with consequences for cancer cell motility and cortical neuronal development (PMID:33475085, PMID:31704703). In innate immunity, TIPARP suppresses type I interferon production by interacting with IRF3 and disrupting the IRF3:CBP/p300 holocomplex in a catalysis-dependent manner, and its loss or catalytic inactivation causes systemic autoimmunity rescued by Irf3 or Sting deletion (PMID:34375612, PMID:39969510). PARP7 protein is intrinsically short-lived, with turnover tuned by auto-MARylation and extended by androgen signaling, and it functions as a nuclear NAD+ sensor that gates adipogenesis through a p300–H3K27ac–C/EBPβ axis (PMID:33572475, PMID:41621069). Pharmacological PARP7 inhibition (RBN-2397) restores interferon signaling and drives antitumor immunity (PMID:34375612).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2010 High

    Established that TIPARP is a functional effector downstream of AHR, answering whether AHR-induced TIPARP has metabolic consequences by linking it to suppression of hepatic gluconeogenesis.

    Evidence Gain/loss-of-function in hepatic cells with glucose output, NAD+, and PGC1α readouts

    PMID:20876576

    Open questions at the time
    • Direct enzymatic targets of TIPARP in this pathway not yet defined
    • NAD+-depletion mechanism inferred rather than directly resolved
  2. 2012 High

    Defined TIPARP's core molecular identity as an auto-mono-ADP-ribosyltransferase and a negative-feedback repressor of AHR, answering how the AHR transcriptional output is constrained.

    Evidence In vitro ADP-ribosylation, RNAi, reporter assays, mutagenesis, Co-IP, and Tiparp-/- MEFs

    PMID:23275542

    Open questions at the time
    • Direct MARylation sites on AHR not mapped
    • E3 ligase mediating AHR degradation not identified
  3. 2013 Medium

    Extended the substrate repertoire by showing TIPARP MARylates PEPCK, connecting AHR-driven TIPARP induction to direct modification of a gluconeogenic enzyme.

    Evidence ADP-ribosylation assays with isoform-specific PEPCK analysis and TIPARP perturbation

    PMID:23770670

    Open questions at the time
    • Functional consequence of PEPCK MARylation on enzyme activity not established
    • MARylation site not mapped
  4. 2014 Medium

    Showed TIPARP repression of AHR is mechanistically independent of AHRR and that TIPARP/PARP1 ADP-ribosylation maintains pluripotency gene loci, broadening TIPARP roles beyond xenobiotic signaling.

    Evidence Double-mutant epistasis/rescue in MEFs; ChIP and loss-of-function in ES cells

    PMID:24806346 PMID:25034692

    Open questions at the time
    • Direct chromatin substrates at pluripotency loci unresolved
    • Mechanism distinguishing TIPARP vs AHRR repression not molecularly defined
  5. 2015 High

    Identified TIPARP MARylation of AHR and its eraser MACROD1, establishing a complete writer/eraser cycle and confirming physiological importance through dioxin-sensitive Tiparp-/- mice.

    Evidence In vitro ribosylation, Tiparp-/- mouse model, MACROD1/2 reversal assays

    PMID:25975270

    Open questions at the time
    • AHR modification residues not pinpointed
    • Whether MACROD1 reverses TIPARP marks on other substrates not tested here
  6. 2016 High

    Demonstrated that TIPARP can positively coactivate a transcription factor (LXRα/β), showing its MARylation output is not uniformly repressive.

    Evidence In vitro ribosylation, reporter assays, Co-IP, peptide array, Tiparp-/- mice

    PMID:26814197

    Open questions at the time
    • Molecular basis for coactivation vs degradation outcome unresolved
    • LXR MARylation sites not mapped
  7. 2018 High

    Mapped TIPARP's domain architecture—nuclear localization determinants, minimal catalytic region, target residue chemistry (Cys/acidic), and an auto-MARylation site (Cys39)—and showed hepatocyte-autonomous requirement for AHR control.

    Evidence Deletion/mutagenesis, inhibitor sensitivity, ETD mass spectrometry; hepatocyte-specific conditional knockout with dioxin challenge

    PMID:29873790 PMID:30373764

    Open questions at the time
    • C39 auto-MARylation function only modestly affects activity
    • Catalytic mechanism and substrate selection rules incomplete
  8. 2019 Medium

    Connected TIPARP α-tubulin MARylation to cortical development, addressing whether its cytoskeletal substrate has organismal consequence.

    Evidence Tiparp-/- mice, cortical layer immunostaining, neural progenitor/migration assays, α-tubulin MAR assay

    PMID:31704703

    Open questions at the time
    • Direct causal link between tubulin MARylation and layering defect not isolated
    • α-tubulin MAR site not mapped here
  9. 2020 High

    Revealed the nuclear-body/condensate mechanism by which TIPARP recruits HUWE1 to ubiquitinate and degrade HIF-1α, c-Myc, and ERα, generalizing TIPARP as a degradative regulator of oncogenic transcription factors.

    Evidence Live-cell imaging, Co-IP, ubiquitination assays, ADP-ribosylation-deficient mutants, xenografts

    PMID:32482854

    Open questions at the time
    • Condensate composition and assembly rules incompletely defined
    • Substrate MARylation sites not all mapped
  10. 2021 High

    Defined PARP7 substrate chemistry proteome-wide (cysteine-preferring MARylation, including PARP-13 and α-tubulin), mapped additional transcription-factor substrates (ERα, AR), and showed androgen-controlled rapid turnover—while CUL4B was implicated in AHR degradation and RBN-2397 inhibition was shown to restore interferon-driven antitumor immunity.

    Evidence Chemical-genetic analog-sensitive PARP7, proteome-wide MS site mapping, domain mutagenesis, KO phenotypes, cycloheximide chase, and RBN-2397 in tumor models

    PMID:33475084 PMID:33475085 PMID:33572475 PMID:33799807 PMID:34146543 PMID:34264286 PMID:34375612

    Open questions at the time
    • Rules governing substrate selection among cysteine sites unclear
    • Relative contribution of distinct E3 ligases (CUL4B vs others) to AHR degradation not fully resolved
  11. 2022 Medium

    Showed PARP7 catalytic activity controls its own protein levels and that inhibitor-induced PARP7 stabilization correlates with interferon induction, while CRISPR screens established AHR (and cohesin) as determinants of inhibitor sensitivity.

    Evidence Two structurally distinct inhibitors with IFN-β reporters and protein quantification; genome-wide CRISPR screen with AHR modulator co-treatments

    PMID:35439318 PMID:36529140

    Open questions at the time
    • Mechanism coupling PARP7 stabilization to IFN magnitude not fully resolved
    • Cohesin's role in inhibitor response mechanistically undefined
  12. 2023 High

    Established that PARP7 MARylation can be protective (FRA1 Cys97 ADP-ribosylation blocks degradation) and that PARP7 modifies RelA/NF-κB, refining how it gates cytokine, apoptotic, and interferon programs.

    Evidence RBN-2397, FRA1 C97 mutagenesis, Co-IP, proteasome inhibition, gene profiling; PARP7 KO syngeneic vs immunodeficient tumor models

    PMID:37509350 PMID:38011562

    Open questions at the time
    • How the same enzyme protects FRA1 but degrades other substrates unresolved
    • RelA MARylation site and functional output incompletely defined
  13. 2025 High

    Resolved the ADP-ribosyl degron pathway in molecular detail—PARP7 generates an ADP-ribose degron on chromatin-bound AR read by DTX2, DTX2 also degrades auto-MARylated PARP7 and AHR, PARP7 disrupts the IRF3:CBP/p300 holocomplex by MARylating p300/CBP and IRF3, and PARP7 acts as a nuclear NAD+ sensor and proteotoxic-stress sensor with roles in adipogenesis, lung barrier, and renal inflammation.

    Evidence In vitro reconstitution, AR DNA-binding mutants, DTX2/E3 identification, chemical genetics, Parp7-/-/Parp7H532A and rescue mouse models, ChIP-seq, and stress/aggresome cell biology

    PMID:39969510 PMID:40493189 PMID:40631120 PMID:40681873 PMID:40836037 PMID:41326691 PMID:41621069 PMID:41779776 PMID:41952113

    Open questions at the time
    • Unified rules determining substrate-specific degradation vs activity modulation not fully formalized
    • Structural basis of degron recognition by reader E3 ligases incompletely defined
    • p300/CBP holocomplex work partly from preprint pending peer review

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TIPARP integrates its many context-dependent outputs—degradative vs protective MARylation, NAD+ sensing, condensate formation, and tissue-specific physiology—into a single predictive substrate-selection logic remains unresolved.
  • No unified model predicting which substrates are degraded vs stabilized vs coactivated
  • Structural determinants of cysteine site selection unmapped
  • Physiological NAD+ thresholds governing sensor behavior across tissues undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0140110 transcription regulator activity 4 GO:0016740 transferase activity 3 GO:0140299 molecular sensor activity 2
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 3
Partners
AHRARDTX2ESR1HIF1AHUWE1IRF3MACROD1

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 TiPARP/ARTD14 exhibits auto-mono-ADP-ribosyltransferase activity and ribosylates core histones in vitro. RNAi-mediated knockdown of TiPARP increased TCDD-dependent CYP1A1 and CYP1B1 mRNA expression and AHR recruitment to both genes. TiPARP and AHR co-localized in the nucleus, directly interacted, and both were recruited to CYP1A1 in response to TCDD. TiPARP-mediated inhibition of AHR required both the zinc-finger and catalytic domains. Overexpression of TiPARP enhanced TCDD-dependent AHR proteolytic degradation, while knockdown reduced it. TiPARP thus functions as a mono-ADP-ribosyltransferase and transcriptional repressor of AHR, establishing a negative feedback loop in AHR signalling. In vitro ADP-ribosylation assay, RNAi knockdown, reporter gene assay, deletion/mutagenesis studies, co-localization (immunofluorescence), co-immunoprecipitation, Tiparp-/- MEFs Nucleic acids research High 23275542
2010 TiPARP (PARP7) mediates TCDD-induced suppression of hepatic gluconeogenesis downstream of AHR. TiPARP overexpression reproduced TCDD effects on glucose output and NAD+ levels, increased PGC1α acetylation and decreased PGC1α levels; TiPARP silencing diminished these effects. The mechanism involves TiPARP-driven NAD+ depletion, reduced SIRT1 activation of PGC1α, and consequently reduced PEPCK and G6Pase expression. TiPARP overexpression and RNAi knockdown in hepatic cells, glucose output assay, NAD+ measurement, PGC1α acetylation/protein level assessment The Journal of biological chemistry High 20876576
2015 TIPARP mono-ADP-ribosylates AHR (but not ARNT/AHR nuclear translocator). Loss of Tiparp in mice increases sensitivity to dioxin-induced steatohepatitis and lethality. The repressive effect of TIPARP on AHR is reversed by the macrodomain-containing mono-ADP-ribosylase MACROD1 but not MACROD2, establishing MACROD1 as the eraser of TIPARP-placed ADP-ribose marks on AHR. In vitro ADP-ribosylation assay, Tiparp-/- mouse model, MACROD1/MACROD2 reversal assay, reporter gene assay The Journal of biological chemistry High 25975270
2016 TIPARP mono-ADP-ribosylates LXRα and LXRβ and positively regulates their transcriptional activity. TIPARP zinc-finger and catalytic domains are required for LXR co-activation. LXRs interact with an N-terminal sequence (aa 209–236) of TIPARP. MACROD1 (but not MACROD2) interacts with LXRs in a TIPARP-dependent manner and prevents the TIPARP-dependent increase in LXR activity. In vivo, GW3965-dependent increases in hepatic Srebp1 mRNA/protein were reduced in Tiparp-/- mice. In vitro ADP-ribosylation assay, reporter gene assay, TIPARP KD/KO, co-immunoprecipitation, peptide array, immunofluorescence, Tiparp-/- mice The Biochemical journal High 26814197
2018 TIPARP nuclear localization depends on a short N-terminal sequence and its zinc finger domain. The minimum catalytically active region spans amino acids 400–657 and retains AHR mono-ADP-ribosylation ability. Catalytic activity is sensitive to iodoacetamide and hydroxylamine (implicating cysteines and acidic residues as targets) but resistant to meta-iodobenzylguanidine. Mass spectrometry identified cysteine 39 via ETD as a site of TIPARP auto-mono-ADP-ribosylation; C39A mutation modestly reduced autoribosylation but did not prevent AHR repression. Deletion/mutagenesis studies, in vitro ADP-ribosylation assay, chemical inhibitor sensitivity assays, mass spectrometry with ETD, immunofluorescence localization The Biochemical journal High 30373764
2014 Parp1 and Parp7 co-occupy key pluripotency gene loci (Nanog, Pou5f1, Sox2, Stella, Tet1, Zfp42) in embryonic stem cells, protecting them from epigenetic repression. Loss of either Parp1 or Parp7, or inhibition of ADP-ribosylating activity, decreases ground-state pluripotency and increases the propensity of ES cells to differentiate. ChIP, ADP-ribosylation inhibition, Parp1/Parp7 loss-of-function in ES cells, pluripotency marker analysis Nucleic acids research Medium 25034692
2014 AHRR and TiPARP independently repress AHR transactivation by distinct mechanisms: TiPARP knockdown (but not AHRR knockdown) increased AHR protein levels and TCDD-induced CYP1A1 mRNA. Overexpression of TiPARP in AHRR-/- MEFs reduced CYP1A1 induction, and vice versa, confirming independent repression pathways. Nuclear localization of AHRR is required for its repressive function. RNAi knockdown, Tiparp-/- and Ahrr-/- MEFs, overexpression rescue experiments, reporter gene assay, immunofluorescence International journal of molecular sciences Medium 24806346
2018 Hepatocyte-specific deletion of TIPARP (Tiparpfl/flCreAlb mice) is sufficient to increase sensitivity to dioxin-induced steatohepatitis and lethality, demonstrating that TIPARP's negative regulation of AHR is functionally critical specifically in hepatocytes. Cre-lox conditional knockout (hepatocyte-specific), dioxin challenge, liver pathology, AHR target gene expression, metabolomics Toxicological sciences High 29873790
2020 TiPARP forms distinct ADP-ribosylation-dependent nuclear condensates/nuclear bodies that recruit HIF-1α and the E3 ubiquitin ligase HUWE1, promoting ubiquitination and proteasomal degradation of HIF-1α. TiPARP similarly promotes degradation of c-Myc and estrogen receptor via this nuclear body mechanism, functioning as a negative-feedback regulator for multiple oncogenic transcription factors. Live-cell imaging of nuclear condensates, co-immunoprecipitation, ubiquitination assay, ADP-ribosylation-deficient mutants, xenograft tumor models Proceedings of the National Academy of Sciences of the United States of America High 32482854
2021 PARP7 is a negative regulator of nucleic acid sensing in tumor cells. Inhibition of PARP7 by RBN-2397 restores type I interferon signaling responses to nucleic acids, directly inhibiting cell proliferation and activating antitumor immunity. Complete tumor regression in a lung cancer xenograft model was observed upon oral PARP7 inhibition, dependent on type I IFN signaling in tumor cells. PARP7 inhibitor (RBN-2397), xenograft and immunocompetent mouse tumor models, IFN signaling assays, cell proliferation assays, immune cell analyses Cancer cell High 34375612
2021 PARP-7 preferentially MARylates cysteine residues. Using chemical genetics and proteome-wide ADP-ribosylation site profiling, PARP-13 was identified as a major direct target of PARP-7 MARylation, specifically on cysteine residues within its RNA-binding zinc finger domain. Proteome-wide analysis confirmed cysteine as the predominant MARylation acceptor for PARP-7. Chemical genetics (analog-sensitive PARP-7), proximity labeling, proteome-wide ADP-ribosylation site mapping by mass spectrometry eLife High 33475084
2021 PARP-7 MARylates α-tubulin to promote microtubule instability, which regulates ovarian cancer cell growth and motility. An NAD+ analog-sensitive approach coupled with mass spectrometry identified α-tubulin and other cytoskeletal/cell-adhesion proteins as components of the PARP-7 ADP-ribosylated proteome in ovarian cancer cells. NAD+ analog-sensitive PARP-7 coupled with mass spectrometry, PARP-7 depletion, cell growth/migration assays, global gene expression analysis eLife High 33475085
2021 PARP7 mono-ADP-ribosylates estrogen receptor α (ERα), with modification sites mapped by mass spectrometry to the receptor's ligand-independent transactivation domain; the hinge region of ERα is required for PARP7-dependent mono-ADP-ribosylation. PARP7 overexpression decreases ligand-dependent ERα signaling; PARP7 KO MCF-7 cells show increased ERα target gene expression and proliferation in response to 17β-estradiol. Co-immunoprecipitation, mass spectrometry, truncated ERα variants, reporter gene assay, PARP7 KO cells Cells High 33799807
2021 PARP7 mono-ADP-ribosylates the androgen receptor (AR) in the nucleus, requiring nuclear localization of PARP7 and an agonist-induced conformation of AR. The Cys3His1-type zinc finger (ZF) of PARP7 is critical for efficient nuclear import and for AR ADP-ribosylation independently of catalytic activity. ZF mutations abolish PARP7 enhancement of AR-dependent transcription of MYBPC1 without reducing PARP7's catalytic activity or AR binding. Nuclear localization studies, conformation-specific AR mutants, ZF mutagenesis, in vitro/cellular ADP-ribosylation assays, AR-dependent reporter gene assay The Biochemical journal High 34264286
2021 PARP7 protein has an extremely short half-life (~4.5 min) that is extended by androgen/AR signaling (~25.6 min), leading to nuclear accumulation. Androgen-dependent post-transcriptional stabilization of PARP7 is distinct from transcriptional regulation. Mutations in the catalytic domain, zinc finger, and WWE domains each reduce PARP7 degradation rate, indicating that the overall protein structure is tuned for rapid turnover. Cycloheximide chase assay, androgen treatment, domain mutagenesis, subcellular fractionation, comparison with PARP1/2/9/14 Cells Medium 33572475
2021 TiPARP controls TCDD-activated AHR nuclear export and subsequent proteasomal degradation. In MEFCul4b-null cells, TiPARP knockdown completely abolished AHR degradation upon TCDD treatment, while CUL4B deletion only partially prevented it. Combined loss of CUL4B and TiPARP led to enhanced AHR transcriptional activity. Cul4b-null MEFs, TiPARP siRNA knockdown, AHR protein levels and nuclear export assay, AHR target gene expression The Journal of biological chemistry Medium 34146543
2021 TIPARP catalytic activity is required for its role as a negative regulator of AHR in vivo. Catalytically deficient TiparpH532A knock-in mice exhibit increased TCDD-induced AHR target gene expression, steatohepatitis, hepatotoxicity, and lethality at doses non-lethal to wild-type mice, demonstrating that H532 is the critical catalytic residue. Catalytic knock-in mouse model (H532A point mutation), TCDD challenge, hepatic RNA-seq, liver pathology, AHR target gene expression Toxicological sciences High 34129049
2013 TCDD-induced TiPARP ADP-ribosylates PEPCK (both cytosolic and mitochondrial forms) as a downstream posttranslational modification, identifying PEPCK as a TiPARP substrate and linking AHR transcriptional activation of TiPARP to a downstream change in a gluconeogenic enzyme. In vitro/cellular ADP-ribosylation assay, TCDD treatment, TiPARP knockdown/overexpression, isoform-specific PEPCK analysis The Journal of biological chemistry Medium 23770670
2019 Loss of Tiparp results in aberrant cortical layering with increased upper-layer cell density, predominantly affecting GABAergic neuron distribution and number. Neural progenitor cell proliferation is reduced, and Tiparp-/- neural stem cells show slower migration. α-tubulin mono-ADP-ribosylation levels are reduced in Tiparp-/- cells, suggesting Tiparp mediates α-tubulin MAR during cortical development. Tiparp-/- mouse model, cortical layer immunostaining, neural progenitor proliferation assay, neural stem cell migration assay, α-tubulin MAR assay eNeuro Medium 31704703
2023 PARP7 ADP-ribosylates the AP-1 transcription factor FRA1 on cysteine 97 in the nucleus. FRA1 ADP-ribosylation protects it from proteasomal degradation via PSMC3. Loss of FRA1 ADP-ribosylation (via PARP7 inhibition or C97 mutation) promotes IRF1- and IRF3-dependent cytokine and proapoptotic gene expression, culminating in CASP8-mediated apoptosis. PARP7 inhibitor (RBN-2397), ADP-ribosylation site mutagenesis (FRA1 C97), Co-IP, proteasome inhibition, gene expression profiling Proceedings of the National Academy of Sciences of the United States of America High 38011562
2022 PARP7 inhibition synergistically induces IFN-β expression when combined with nucleic acid sensor ligands in MEFs; PARP7 catalytic activity regulates its own protein levels (PARP7 inhibition increases PARP7 protein). Two structurally distinct inhibitors (KMR-206 and RBN-2397) achieve different PARP7 protein stabilization levels correlating with different magnitudes of IFN gene induction. PARP7 inhibitor treatment (KMR-206, RBN-2397), IFN-β reporter assays, PARP7 protein level quantification, comparison of structurally distinct inhibitors Cell chemical biology Medium 36529140
2022 AHR loss confers resistance to PARP7 inhibitor (RBN-2397) treatment, identified in a genome-wide CRISPR screen. Components of the cohesin complex also emerge as determinants of RBN-2397 resistance. AHR activators and inhibitors modulate cellular response to PARP7 inhibition, establishing epistatic dependence of PARP7 inhibitor sensitivity on AHR. Genome-wide CRISPR screen, AHR modulator co-treatments, cell viability assays Molecular cancer therapeutics Medium 35439318
2023 Loss of PARP7 expression increases type I IFN signaling, including ISGF3 and unphosphorylated-ISGF3 regulated target genes, partly because PARP7 modifies the RelA subunit of NF-κB. PARP7 loss had no effect on tumor growth in immunodeficient mice but prevented tumor development in immunocompetent settings, demonstrating immune-cell-dependent tumor suppression. PARP7 KO EO771 cells, syngeneic mouse tumor model, immunodeficient mouse controls, IFN signaling pathway analysis, NF-κB RelA ADP-ribosylation Cancers Medium 37509350
2025 PARP7 generates an ADP-ribosyl degron in the DNA-binding domain of AR on chromatin, recognized by the ADP-ribose reader domain of the ubiquitin E3 ligase DTX2 (not DTX3L), leading to proteasomal degradation of AR. Mathematical modeling and an AR DNA-binding mutant confirmed that PARP7 ADP-ribosylates chromatin-bound AR. This constitutes a negative feedback loop regulating modules of AR target genes. In vitro/cellular ADP-ribosylation assay, AR DNA-binding mutant, DTX2 interaction and ubiquitination assay, mathematical modeling, chromatin fractionation The EMBO journal High 40681873
2025 PARP7 inhibits the IRF3:CBP/p300 transcriptional holocomplex required for IFN-I production by MARylating p300 and CBP. An α-helical domain in PARP7 is essential for p300/CBP interaction, MARylation, and proteasome degradation of p300/CBP. Disrupting PARP7-p300/CBP interaction prevents PARP7's suppression of IFN-β. p300/CBP reciprocally regulate PARP7 activity and nuclear localization. Chemical genetic ASCG approach (analog-sensitive), Co-IP, domain deletion, IFN-β reporter assays, PARP7 KO vs inhibitor comparison bioRxivpreprint Medium 40631120
2025 PARP7 interacts with IRF3 through its catalytic domain and disrupts the IRF3:CBP/p300 transcriptional holocomplex required for IFN-I production in a MARylation-dependent manner. Parp7-/- and Parp7H532A/H532A mice develop systemic autoimmunity and pulmonary tertiary lymphoid structures; Irf3-/-, Irf3S1/S1 (transcription-defective), or Sting-/- genetically rescues Parp7H532A/H532A autoimmunity and lung disease. Parp7-/- and ParpH532A/H532A mice, IRF3 Co-IP, genetic rescue with Irf3-/-, Irf3S1/S1, Sting-/-, autoimmunity phenotype analysis The Journal of experimental medicine High 39969510
2025 DTX2 is the E3 ligase responsible for degrading ADP-ribosylated PARP7, AHR, and other PARP7 substrates. Endogenous ADP-ribosylation of PARP7 and AHR is greatly induced when the ubiquitin-proteasome pathway is blocked, and AHR pathway activation promotes quantitative ADP-ribosylation of PARP7 itself (auto-MARylation) and AHR. This establishes mono-ADP-ribosylation as a degradation mark. Ubiquitin pathway blockade (proteasome inhibitors), ADP-ribosylation detection, DTX2 identification as E3 ligase, AHR pathway activation, endogenous protein level analyses The EMBO journal High 41326691
2025 PARP7 functions as a nuclear NAD+ sensor for adipogenesis: at higher nuclear NAD+ concentrations in undifferentiated preadipocytes, PARP7 undergoes auto-MARylation, which promotes its own proteasomal degradation via DTX2 and RNF114 E3 ligases. Stabilized PARP7 (when NAD+ declines post-differentiation) serves as a coregulator of C/EBPβ by stimulating p300-mediated H3K27 acetylation and C/EBPβ genomic binding. Genetic PARP7 depletion in mice reduces adipogenesis, fat mass, and milk lipid composition. NAD+ measurement, autoMARylation assay, DTX2/RNF114 KO, ChIP-seq (C/EBPβ binding, H3K27ac), PARP7 KO mice with mammary gland and fat pad phenotyping, metabolomics Cell reports High 41621069
2025 PARP7 is a proteotoxic stress sensor: during proteotoxic stress, PARP7 protein is stabilized and mono-ADP-ribosylates proteins that accumulate in cytoplasmic foci containing ubiquitin and p62, and are subsequently trafficked to aggresomes for autophagic degradation. Ubiquitination is required for efficient clearance of ADP-ribosylated proteins; PARP7 inhibition impedes accumulation of MARylated proteins in response to proteotoxic stress. Proteotoxic stress treatment, PARP7 inhibition, ADP-ribosylation immunofluorescence, aggresome imaging, ubiquitin pathway inhibition, PARP7 protein stability assays The EMBO journal Medium 40836037
2025 PARP7 is selectively expressed in alveolar type I cells and maintains lung epithelial barrier integrity. PARP7 loss increases susceptibility to chemically induced diffuse alveolar hemorrhaging and pristane-induced lupus with increased immune infiltration. Mechanistically, PARP7 acts via AHR to control tight junction protein Occludin and xenobiotic/inflammatory gene expression in bronchial epithelial cells upon cigarette smoke or bacterial challenge. Parp7-/- mice, chemical challenge models, single-nucleus RNA-seq, air-liquid interface culture, PARP7 inhibitor treatment in human bronchial epithelial cells, AHR epistasis Proceedings of the National Academy of Sciences of the United States of America Medium 41779776
2025 PARP7 interacts with TBK1 and mediates its ADP-ribosylation in LPS-stimulated renal tubular epithelial cells, suppressing TBK1-driven inflammation. The anti-inflammatory effects of PARP7 are dependent on its catalytic residue H532. PARP7-specific overexpression in renal proximal tubular cells attenuated septic AKI in mice, while global PARP7 deletion exacerbated LPS-induced renal inflammation. Co-immunoprecipitation, H532 catalytic mutant, PARP7 overexpression in vivo, PARP7 global KO, LPS-AKI mouse model, scRNA-seq Molecular medicine Medium 41952113
2025 SOCS3 crosstalks with AHR in the context of PARP7 signaling: PARP7 inhibition in SOCS3 knockout cells leads to reduced cell viability compared with wild-type cells. AHR transcriptional activity remodels the proteome upon PARP7 inhibition, including downregulation of filamins A and B concurrent with induction of the E3 ubiquitin ligase ASB2. Genome-wide CRISPR screens, multiplex quantitative proteomics, SOCS3 KO cells, PARP7 inhibitor treatment Proceedings of the National Academy of Sciences of the United States of America Medium 40493189

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: implications for cerebral ischemic stroke. Autophagy 320 29938598
2019 Circular RNA TLK1 Aggravates Neuronal Injury and Neurological Deficits after Ischemic Stroke via miR-335-3p/TIPARP. The Journal of neuroscience : the official journal of the Society for Neuroscience 180 31311824
2021 PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity. Cancer cell 143 34375612
2012 2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymerase (TiPARP, ARTD14) is a mono-ADP-ribosyltransferase and repressor of aryl hydrocarbon receptor transactivation. Nucleic acids research 142 23275542
2010 Identification of the aryl hydrocarbon receptor target gene TiPARP as a mediator of suppression of hepatic gluconeogenesis by 2,3,7,8-tetrachlorodibenzo-p-dioxin and of nicotinamide as a corrective agent for this effect. The Journal of biological chemistry 97 20876576
2020 TiPARP forms nuclear condensates to degrade HIF-1α and suppress tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America 84 32482854
2003 Identification and characterization of human TIPARP gene within the CCNL amplicon at human chromosome 3q25.31. International journal of oncology 74 12851707
2021 Chemical genetics and proteome-wide site mapping reveal cysteine MARylation by PARP-7 on immune-relevant protein targets. eLife 71 33475084
2014 ADP-ribosyltransferases Parp1 and Parp7 safeguard pluripotency of ES cells. Nucleic acids research 66 25034692
2021 Identification of PARP-7 substrates reveals a role for MARylation in microtubule control in ovarian cancer cells. eLife 64 33475085
2015 Loss of the Mono-ADP-ribosyltransferase, Tiparp, Increases Sensitivity to Dioxin-induced Steatohepatitis and Lethality. The Journal of biological chemistry 63 25975270
2018 Characterization of TCDD-inducible poly-ADP-ribose polymerase (TIPARP/ARTD14) catalytic activity. The Biochemical journal 58 30373764
2016 TCDD-inducible poly-ADP-ribose polymerase (TIPARP/PARP7) mono-ADP-ribosylates and co-activates liver X receptors. The Biochemical journal 53 26814197
2021 PARP7 and Mono-ADP-Ribosylation Negatively Regulate Estrogen Receptor α Signaling in Human Breast Cancer Cells. Cells 51 33799807
2024 Design, Synthesis, and Structure-Activity Relationship of Novel Pyridazinone-Based PARP7/HDACs Dual Inhibitors for Elucidating the Relationship between Antitumor Immunity and HDACs Inhibition. Journal of medicinal chemistry 50 38456618
2014 Aryl hydrocarbon receptor repressor and TiPARP (ARTD14) use similar, but also distinct mechanisms to repress aryl hydrocarbon receptor signaling. International journal of molecular sciences 49 24806346
2022 Structurally distinct PARP7 inhibitors provide new insights into the function of PARP7 in regulating nucleic acid-sensing and IFN-β signaling. Cell chemical biology 39 36529140
2023 PARP7-mediated ADP-ribosylation of FRA1 promotes cancer cell growth by repressing IRF1- and IRF3-dependent apoptosis. Proceedings of the National Academy of Sciences of the United States of America 37 38011562
2021 Roles of the ubiquitin ligase CUL4B and ADP-ribosyltransferase TiPARP in TCDD-induced nuclear export and proteasomal degradation of the transcription factor AHR. The Journal of biological chemistry 31 34146543
2021 Post-Transcriptional Regulation of PARP7 Protein Stability Is Controlled by Androgen Signaling. Cells 30 33572475
2021 PARP7 mono-ADP-ribosylates the agonist conformation of the androgen receptor in the nucleus. The Biochemical journal 27 34264286
2018 Hepatocyte-Specific Deletion of TIPARP, a Negative Regulator of the Aryl Hydrocarbon Receptor, Is Sufficient to Increase Sensitivity to Dioxin-Induced Wasting Syndrome. Toxicological sciences : an official journal of the Society of Toxicology 26 29873790
2023 Loss of PARP7 Increases Type I Interferon Signaling in EO771 Breast Cancer Cells and Prevents Mammary Tumor Growth by Increasing Antitumor Immunity. Cancers 25 37509350
2022 A Whole-Genome CRISPR Screen Identifies AHR Loss as a Mechanism of Resistance to a PARP7 Inhibitor. Molecular cancer therapeutics 24 35439318
2017 The aryl hydrocarbon receptor regulates the expression of TIPARP and its cis long non-coding RNA, TIPARP-AS1. Biochemical and biophysical research communications 24 29274782
2013 Aryl hydrocarbon receptor activation by dioxin targets phosphoenolpyruvate carboxykinase (PEPCK) for ADP-ribosylation via 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP-ribose) polymerase (TiPARP). The Journal of biological chemistry 24 23770670
2019 TCDD-Inducible Poly-ADP-Ribose Polymerase (TIPARP), A Novel Therapeutic Target Of Breast Cancer. Cancer management and research 21 31695491
2025 PARP7 as a new target for activating anti-tumor immunity in cancer. EMBO molecular medicine 19 40128585
2023 Induction of PARP7 Creates a Vulnerability for Growth Inhibition by RBN2397 in Prostate Cancer Cells. Cancer research communications 17 37077937
2024 Novel Bifunctional Conjugates Targeting PD-L1/PARP7 as Dual Immunotherapy for Potential Cancer Treatment. Journal of medicinal chemistry 16 38912753
2021 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)-Inducible Poly-ADP-Ribose Polymerase (TIPARP/PARP7) Catalytic Mutant Mice (TiparpH532A) Exhibit Increased Sensitivity to TCDD-Induced Hepatotoxicity and Lethality. Toxicological sciences : an official journal of the Society of Toxicology 16 34129049
2023 Chorioallantoic membrane assay revealed the role of TIPARP (2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible poly (ADP-ribose) polymerase) in lung adenocarcinoma-induced angiogenesis. Cancer cell international 15 36841751
2022 Reduced Colonic Mucosal Injury in 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Poly ADP-Ribose Polymerase (TIPARP/PARP7)-Deficient Mice. International journal of molecular sciences 14 35055106
2021 LncRNA XIST Promoted OGD-Induced Neuronal Injury Through Modulating/miR-455-3p/TIPARP Axis. Neurochemical research 13 33738662
2019 Loss of Tiparp Results in Aberrant Layering of the Cerebral Cortex. eNeuro 13 31704703
2025 PARP7 Inhibitors and AHR Agonists Act Synergistically across a Wide Range of Cancer Models. Molecular cancer therapeutics 12 39313957
2023 Discovery of Highly Selective PARP7 Inhibitors with a Novel Scaffold for Cancer Immunotherapy. Journal of medicinal chemistry 12 38059836
2025 PARP7 inhibits type I interferon signaling to prevent autoimmunity and lung disease. The Journal of experimental medicine 11 39969510
2024 New TIPARP inhibitor rescues mitochondrial function and brain injury in ischemic stroke. Pharmacological research 11 39547463
2019 3-Methylcholanthrene Induces Chylous Ascites in TCDD-Inducible Poly-ADP-Ribose Polymerase (Tiparp) Knockout Mice. International journal of molecular sciences 11 31083300
2025 CRISPR screens and quantitative proteomics reveal remodeling of the aryl hydrocarbon receptor-driven proteome through PARP7 activity. Proceedings of the National Academy of Sciences of the United States of America 9 40493189
2025 Parp7 generates an ADP-ribosyl degron that controls negative feedback of androgen signaling. The EMBO journal 9 40681873
2023 PARP7 Inhibition: A Promising Pathway to Advancements in Cancer Therapy. ACS medicinal chemistry letters 8 37736186
2021 Knockdown of lncRNA SNHG15 Ameliorates Oxygen and Glucose Deprivation (OGD)-Induced Neuronal Injury via Regulating the miR-9-5p/TIPARP Axis. Biochemical genetics 8 34453220
2022 TIPARP is involved in the regulation of intraocular pressure. Communications biology 7 36536086
2018 Methods to Study TCDD-Inducible Poly-ADP-Ribose Polymerase (TIPARP) Mono-ADP-Ribosyltransferase Activity. Methods in molecular biology (Clifton, N.J.) 7 30097864
2024 Discovery of highly potent PARP7 inhibitors for cancer immunotherapy. Bioorganic chemistry 5 38781669
2025 Loss of Parp7 increases type I interferon signalling and reduces pancreatic tumour growth by enhancing immune cell infiltration. Frontiers in immunology 4 39867896
2025 The IFN I response in tumor cells is shaped by PARP7-p300/CBP interactions through distinct loss- and gain-of-function mechanisms. bioRxiv : the preprint server for biology 4 40631120
2024 Unleashing viral mimicry: A combinatorial strategy to enhance the efficacy of PARP7 inhibitors. BioEssays : news and reviews in molecular, cellular and developmental biology 4 39502005
2025 NAD + Sensing by PARP7 Regulates the C/EBPβ-Dependent Transcription Program in Adipose Tissue In Vivo. bioRxiv : the preprint server for biology 3 40291749
2023 Quantification of PARP7 Protein Levels and PARP7 Inhibitor Target Engagement in Cells Using a Split Nanoluciferase System. Methods in molecular biology (Clifton, N.J.) 3 36515849
2025 PARP7 is a proteotoxic stress sensor that labels proteins for degradation. The EMBO journal 2 40836037
2025 PARP7: an Emerging Therapeutic Target-Insights into Biological Functions and Advances in Small-Molecule Inhibitor Development. Journal of medicinal chemistry 2 40994152
2025 Ubiquitin pathway blockade reveals endogenous ADP-ribosylation marking PARP7 and AHR for degradation. The EMBO journal 2 41326691
2025 Advances in TCDD-inducible poly(ADP-ribose) polymerase (TiPARP/PARP7) research: From molecular mechanisms to therapeutic applications. Biochemical pharmacology 2 41365471
2011 [Genetic analysis and gene mapping of DDF1, a pleiotropic gene involving in both vegetable and reproductive growth in rice]. Yi chuan = Hereditas 2 22207384
2026 High PARP7 Expression is Associated with Higher Estrogen Response and Immune Suppression but Less Cell Proliferation and Better Survival in Breast Cancer. Annals of surgical oncology 1 41712159
2024 RBN-2397, a PARP7 Inhibitor, Synergizes with Paclitaxel to Inhibit Proliferation and Migration of Ovarian Cancer Cells. bioRxiv : the preprint server for biology 1 39229139
2023 The association between TIPARP gene polymorphisms rs2665390 and ovarian cancer susceptibility. Gynecologic oncology reports 1 37091214
2026 Identification of a Two-Gene Biomarker Correlated with Sensitivity to Combined PARP7 Inhibition and AHR Activation in Cancer Cells. Cancer research communications 0 41295982
2026 NAD+ sensing by PARP7 regulates the C/EBPβ-dependent transcription program during adipogenesis. Cell reports 0 41621069
2026 Design and Synthesis of KRASG12C Inhibitors for Antitumor Evaluation Harboring Combination Therapy with Nrf2, PARP-7, and Pan-USP Inhibitors to Alleviate Drug Resistance Synergistically. Journal of medicinal chemistry 0 41633936
2026 Novel Compounds as TIPARP Inhibitors for Treating Head and Neck Squamous Cell Carcinoma (HNSCC). ACS medicinal chemistry letters 0 41704360
2026 PARP7 protects the lung epithelial barrier from diverse environmental threats. Proceedings of the National Academy of Sciences of the United States of America 0 41779776
2026 PARP7 alleviates lipopolysaccharide-induced acute kidney injury by inhibiting TBK1-driven inflammation in renal tubular epithelial cells. Molecular medicine (Cambridge, Mass.) 0 41952113
2026 PARP7 inhibition and a STING agonist potentiate radiation-induced immunogenicity in glioblastoma. Oncoimmunology 0 41979168
2026 METTL16 Promotes Cerebral Ischemia-Reperfusion Injury via m6A-Dependent Upregulation of TIPARP. International journal of general medicine 0 42004240
2025 PARP7 Suppresses Radiation-induced Necroptosis and Abscopal Immunity. Research square 0 41282221
2025 PARP7 and aryl hydrocarbon receptor differentially regulate mammary cancer cell proliferation and STING-induced type I interferon signalling. Cellular oncology (Dordrecht, Netherlands) 0 41432900

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