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    GENE:

    PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)

    i
    Other names: PARP3, Poly(ADP-Ribose) Polymerase Family Member 3, PADPRT-3, ADPRT3, ARTD3, IRT1, HPARP-3, ADPRTL3, ADP-Ribosyltransferase (NAD+; Poly (ADP-Ribose) Polymerase)-Like 3, ADP-Ribosyltransferase Diphtheria Toxin-Like 3, Protein Mono-ADP-Ribosyltransferase PARP3, DNA ADP-Ribosyltransferase PARP3, NAD(+) ADP-Ribosyltransferase 3, Poly [ADP-Ribose] Polymerase 3, Poly(ADP-Ribose) Synthetase-3, NAD+ ADP-Ribosyltransferase 3, Poly[ADP-Ribose] Synthase 3, ADPRT-3, ADP-Ribosyltransferase (NAD+; Poly (ADP-Ribose) Polymerase)-Like 2, Poly(ADP-Ribose) Polymerase 3, Poly[ADP-Ribose] Synthetase 3, ADPRTL2, PARP-3
    Associations

    News

    Trials
    2ms
    PARPs and PARP inhibitors: molecular mechanisms and clinical applications. (PubMed, Mol Biomed)
    Clinically, PARP inhibitors (PARPi), such as olaparib, niraparib, rucaparib, and talazoparib, exploit synthetic lethality in homologous recombination-deficient tumors and are increasingly applied in ovarian, breast, prostate, and pancreatic cancers. By integrating canonical DNA repair roles with non-canonical signaling and host-virus interactions, PARPs represent pivotal regulators. Similarly, the versatile therapeutics of PARPi have implications that extend beyond oncology into a broader and diverse range of other human diseases.
    Review • Journal • PARP Biomarker
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    HRD (Homologous Recombination Deficiency) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)
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    Lynparza (olaparib) • Talzenna (talazoparib) • Zejula (niraparib) • Rubraca (rucaparib)
    5ms
    PARP3 Promotes AML Progression via Activation of PI3K/AKT/mTOR Signaling. (PubMed, Cancers (Basel))
    Finally, we confirmed that specifically down-regulating PARP3 expression impaired AML cell proliferation, disrupted cell cycle process, inhibited migration, accelerated apoptosis, and impaired the PI3K/AKT/mTOR signaling pathway in vitro. PARP3-mediated activation of the PI3K/AKT/mTOR signaling pathway enhances AML cell proliferation and migration, identifying it as a potential therapeutic target for poor-prognosis AML.
    Journal • PARP Biomarker
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    PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)
    5ms
    SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry (clinicaltrials.gov)
    P=N/A, N=50000, Recruiting, Massive Bio, Inc. | Trial completion date: Jun 2027 --> Jun 2040 | Trial primary completion date: Dec 2026 --> Dec 2038
    Trial completion date • Trial primary completion date
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • CLDN18 (Claudin 18) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • NRG1 (Neuregulin 1) • POLE (DNA Polymerase Epsilon) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • KDR (Kinase insert domain receptor) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • VEGFA (Vascular endothelial growth factor A) • BCL6 (B-cell CLL/lymphoma 6) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • FGFR4 (Fibroblast growth factor receptor 4) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • TSC2 (TSC complex subunit 2) • CHEK2 (Checkpoint kinase 2) • PD-L2 (Programmed Cell Death 1 Ligand 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • JAK1 (Janus Kinase 1) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • MDM4 (The mouse double minute 4) • POLD1 (DNA Polymerase Delta 1) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • AURKA (Aurora kinase A) • JAK3 (Janus Kinase 3) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • CHEK1 (Checkpoint kinase 1) • GATA6 (GATA Binding Protein 6) • MSH3 (MutS Homolog 3) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • GNAS (GNAS Complex Locus) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3) • CSF1R (Colony stimulating factor 1 receptor) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • HDAC1 (Histone Deacetylase 1) • PRDM1 (PR/SET Domain 1) • ZNF217 (Zinc Finger Protein 217) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • GATA3 (GATA binding protein 3) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • ACVR1B (Activin A Receptor Type 1B) • ZNF703 (Zinc Finger Protein 703)
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    HER-2 mutation • AKT1 mutation
    7ms
    Mono-ADP-ribosylating PARP enzymes in cellular signaling and disease. (PubMed, J Cell Sci)
    We then describe what is known about the roles of MARylating PARP proteins in the context of viral infection and cancer. Finally, we discuss potential future directions towards mapping out the complex network of PARP targets and functions.
    Review • Journal
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    PARP1 (Poly(ADP-Ribose) Polymerase 1) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)
    7ms
    Multiple functions of PARP1 in the repair of DNA double strand breaks. (PubMed, DNA Repair (Amst))
    We discuss their influence on chromatin regulation at break sites, their role in repair pathway selection, and finally, the regulation of repair mechanisms, including homologous recombination, non-homologous end-joining, and microhomology-mediated end-joining. Understanding these diverse and sometimes opposing roles is especially important in light of the clinical use of PARP inhibitors in cancers deficient in homologous recombination repair.
    Journal
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    HRD (Homologous Recombination Deficiency) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)
    10ms
    Leveraging Diverse Cell-Death Patterns to Decipher the Interactive Relation of Unfavorable Outcome and Tumor Microenvironment in Breast Cancer. (PubMed, Bioengineering (Basel))
    Our study provided a comprehensive landscape of the cancer survival difference and related PCD-TME interaction axis and highlighted that high-apoptosis/pyroptosis states caused favorable prognosis, underlying mechanisms closely related with the TME where anti-tumor immunity would be beneficial for patient prognosis. These findings highlighted the model's potential for risk stratification in BC.
    Journal • PARP Biomarker
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    TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • CDH1 (Cadherin 1) • NFKBIA (NFKB Inhibitor Alpha 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • PROM2 (Prominin 2)
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    TP53 mutation
    10ms
    Parp3 assists muscle function and skeletal muscle differentiation by selectively adjusting H3K27me3 enrichment. (PubMed, iScience)
    Moreover, Parp3 ADP-ribosylates Ezh2 in vitro. Altogether, these findings unveil Parp3 as a driver of efficient murine skeletal myogenesis in vitro and muscle function in young adults, and highlight an epigenetic control of gene expression.
    Journal • PARP Biomarker
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    PARP1 (Poly(ADP-Ribose) Polymerase 1) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)
    1year
    Novel inhibitors of PARP1 and PARP14: design, synthesis, and potentiation of cisplatin efficacy in cancer. (PubMed, Future Med Chem)
    Compounds 1 and 2 were further investigated using in vitro cell viability assays, which revealed that cells treated with either lead PARP inhibitor and cisplatin in combination had significantly lower survival rates than those treated with cisplatin alone. At 10 µM, the combination showed more significant cell survival reduction, suggesting greater inhibition of PARP increases lethality, particularly in HeLa and PC-3 cell lines at 96 h and beyond.
    Journal
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    PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • TIPARP (TCDD Inducible Poly(ADP-Ribose) Polymerase)
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    PARP1 overexpression
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    cisplatin
    1year
    Candidate genes in canine hepatocellular carcinoma for molecular targeted therapy. (PubMed, BMC Res Notes)
    Sorafenib is a targeted therapy for unresectable canine HCC...Differentially expressed genes (DEGs) between canine HCC and normal liver were explored based on previously reported molecular-targeted agents for human tumours. PARP3, DNMT1, FGF19, FGF23, and RET DEGs were upregulated, whereas KIT, FGFR2, and FGF21 DEGs were downregulated.
    Journal • PARP Biomarker
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    FGFR2 (Fibroblast growth factor receptor 2) • FGF19 (Fibroblast growth factor 19) • DNMT1 (DNA methyltransferase 1) • FGF21 (Fibroblast Growth Factor 21) • FGF23 (Fibroblast Growth Factor 23) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)
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    sorafenib
    over1year
    Functional germline variants in DNA damage repair pathways are associated with altered survival in adults with glioma treated with temozolomide. (PubMed, medRxiv)
    Using a unique dataset that spans the pre- and post-TMZ eras, we demonstrate that germline variation in DDR-related genes may have significant impact on overall survival for patients treated with TMZ, with no effects observed in the pre-TMZ era. This suggests that germline variants in these DDR genes could be used to personalize TMZ therapy to improve patient survival.
    Journal • PARP Biomarker
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    PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • TDG (Thymine DNA Glycosylase)
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    temozolomide
    over1year
    Enhancing Cisplatin Drug Sensitivity through PARP3 Inhibition: The Influence on PDGF and G-Coupled Signal Pathways in Cancer. (PubMed, Chem Biol Interact)
    Moving from bioinformatics to wet lab experiments, cytotoxic experiments demonstrated that the absence of PARP3 by CRISPR/Cas9-mediated knockdown in MDA-MB-231 breast cancer cells increased drug activity towards cisplatin, carboplatin, and doxorubicin. In conclusion, the study demonstrated a synthetic lethal interaction between GPCRs, PDGF signaling pathways, and PARP3 gene silencing. PARP3 emerged as a promising target.
    Journal • PARP Biomarker
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    NEIL3 (Nei Like DNA Glycosylase 3) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)
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    cisplatin • carboplatin • doxorubicin hydrochloride
    almost2years
    Leveraging Shape Screening and Molecular Dynamics Simulations to Optimize PARP1-Specific Chemo/Radio-Potentiators for Antitumor Drug Design. (PubMed, Arch Biochem Biophys)
    Weaker or no interaction was observed for these residues with PARP2 and PARP3. This approach advances our understanding of PARP-1 specific inhibitors and their mechanisms of action, facilitating the development of targeted therapeutics.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA (Breast cancer early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)
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    BRCA mutation