Affinage

DTX3L

E3 ubiquitin-protein ligase DTX3L · UniProt Q8TDB6

Length
740 aa
Mass
83.6 kDa
Annotated
2026-04-28
47 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DTX3L is a RING-type E3 ubiquitin ligase of the Deltex family that functions as a central node integrating ubiquitin signaling, ADP-ribosylation, and nucleic acid modification in DNA damage repair, interferon responses, and cancer biology. DTX3L heterodimerizes with PARP9 via its D3 domain and homo-oligomerizes via D1/D2 domains to form a high-molecular-weight complex that ubiquitylates diverse protein substrates—including histone H4K91, p53, TIRR, TBK1, NLRP3, cGAS, SNAI1, SATB2, LATS2, PKCα, and USP28—targeting many for proteasomal degradation, while also catalyzing NAD⁺-dependent mono-ADP-ribosylation of ubiquitin Gly76 to restrain ubiquitylation, and reading PARP7-generated ADP-ribosylation marks on substrates such as the androgen receptor (PMID:12670957, PMID:28525742, PMID:35037691, PMID:37939374, PMID:38511494). In the DNA damage response, DTX3L is recruited to PARylated damage sites via PARP9, where it monoubiquitylates H4K91 to facilitate 53BP1 recruitment, ubiquitylates TIRR to regulate NHEJ-to-HR pathway choice, degrades p53 at damage foci, and reciprocally regulates DSB repair through mutual antagonism with USP28 (PMID:19818714, PMID:23230272, PMID:37096048, PMID:39632881, PMID:40703443). DTX3L also uniquely ubiquitylates single-stranded DNA and RNA at the 3ʹ-terminal adenosine via ester bond formation through its RING-DTC domains, an activity reversible by deubiquitinases and shared only with DTX3 among Deltex family members (PMID:39377462, PMID:39242775).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2003 High

    Establishing that DTX3L possesses intrinsic E3 ubiquitin ligase activity and that Deltex family members homo- and heterodimerize resolved the basic enzymatic identity of this previously uncharacterized protein.

    Evidence In vitro self-ubiquitination assay and co-immunoprecipitation of DTX family members

    PMID:12670957

    Open questions at the time
    • No physiological substrate identified
    • Dimerization interface unmapped
    • No cellular function established
  2. 2006 Medium

    Demonstrating that DTX3L and PARP9 are co-regulated by an IFN-γ-responsive bidirectional promoter and that DTX3L controls PARP9 subcellular localization linked the E3 ligase to interferon biology and established the obligate functional partnership.

    Evidence Immunofluorescence, reporter assays, and co-expression studies

    PMID:16809771

    Open questions at the time
    • Whether DTX3L directly binds PARP9 was not demonstrated biochemically
    • Functional consequence of relocalization unclear
  3. 2009 High

    Identification of histone H4K91 as the first physiological substrate connected DTX3L to chromatin biology and the DNA damage response, showing that H4K91 monoubiquitylation supports H4K20 methylation and 53BP1 focus formation.

    Evidence In vitro ubiquitylation assay with site-directed mutagenesis and 53BP1 foci immunofluorescence

    PMID:19818714

    Open questions at the time
    • Whether H4K91ub is direct trigger or permissive mark for H4K20me was unresolved
    • Competition with H4K91 acetylation not yet tested
  4. 2012 High

    Showing that PARP9 recruits DTX3L to PARylated DNA damage sites independently of ATM/MDC1/RNF8 established a parallel ubiquitin-dependent DDR pathway that promotes BRCA1 and 53BP1 recruitment.

    Evidence Genetic epistasis in ATM/MDC1/RNF8 knockouts with live-cell imaging and PAR-binding assays

    PMID:23230272

    Open questions at the time
    • Substrates ubiquitylated at damage sites beyond H4 were unknown
    • Relative contribution to repair pathway choice unresolved
  5. 2015 High

    Expanding DTX3L substrates to include host histone H2BJ and viral 3C proteases, and showing STAT1-dependent ISG regulation, established the PARP9-DTX3L complex as a bona fide innate immune effector targeting both host chromatin and viral proteins for degradation.

    Evidence Co-immunoprecipitation, ubiquitin ligase assay, transgenic mouse model, antiviral infection assay

    PMID:26479788

    Open questions at the time
    • Breadth of viral substrates unknown
    • Whether ubiquitylation is K48- or K63-linked on these substrates was not specified
  6. 2015 Medium

    Linking DTX3L to FAK/PI3K/AKT signaling in melanoma invasion and showing that acetylation at H4K91 competes with DTX3L-mediated ubiquitylation extended the functional scope to cancer metastasis and PTM crosstalk.

    Evidence siRNA knockdown with signaling readouts in melanoma; HDAC inhibitor treatment with DSB repair assays

    PMID:25605023 PMID:26033450

    Open questions at the time
    • Direct ubiquitylation targets in FAK pathway not identified
    • Whether H4K91 PTM competition occurs genome-wide or at damage sites specifically was unresolved
  7. 2017 High

    Discovering that the PARP9-DTX3L complex mono-ADP-ribosylates ubiquitin at Gly76 in an NAD⁺-dependent manner—precluding substrate ubiquitylation—revealed a fundamentally new enzymatic activity coupling ADP-ribosylation to ubiquitin regulation.

    Evidence In vitro reconstitution with mass spectrometry, mutagenesis of NAD⁺ binding site

    PMID:28525742

    Open questions at the time
    • Which active site catalyzes the ADP-ribosylation was debated
    • In vivo substrates of ADPr-Ub not identified
    • Reversibility mechanism unknown
  8. 2022 High

    Mapping the D3 domain as the nanomolar-affinity PARP9-binding interface and showing that N-terminal D1/D2 domains drive oligomerization, while demonstrating reversibility of Ub-Gly76 ADP-ribosylation by macrodomain hydrolases, provided the structural logic for the complex.

    Evidence Recombinant reconstitution, quantitative binding measurements, size-exclusion chromatography, in vitro deribosylation

    PMID:35037691

    Open questions at the time
    • No high-resolution structure of the full heterodimer
    • Oligomerization stoichiometry in cells uncertain
  9. 2023 High

    Identifying p53, TBK1, NLRP3, and cGAS as DTX3L ubiquitylation substrates broadened the functional repertoire to encompass tumor suppressor turnover at damage sites, innate immune signaling via TBK1-IFN-β positive feedback, inflammasome regulation, and cGAS-STING suppression in cancer.

    Evidence Co-IP, site-directed mutagenesis of ubiquitylation sites, CRISPR KO with live-cell imaging (p53); ubiquitylation assays with pathway readouts (TBK1, NLRP3, cGAS)

    PMID:36706922 PMID:37096048 PMID:37255478 PMID:37774567

    Open questions at the time
    • Whether all substrates require PARP9 co-factor is unclear
    • Linkage type specificity for each substrate incompletely characterized
  10. 2023 High

    Demonstrating that PARP7-mediated dual ADP-ribosylation of closely spaced cysteines on the androgen receptor is read by the oligomeric DTX3L/PARP9 complex with nanomolar affinity established a 'writer-reader' paradigm for ADP-ribosylation signaling.

    Evidence Synthetic ADP-ribosylated peptide binding assay, fluorescence affinity measurement, oligomerization domain deletion mutagenesis

    PMID:37939374

    Open questions at the time
    • Downstream functional consequence of AR reading is unknown
    • Whether other ADP-ribosylated substrates are similarly read is untested
  11. 2024 High

    Crystal structure of the D2 domain tetramer and functional reconstitution showed that D1-D2-mediated oligomerization is dispensable for PARP9 binding but essential for assembling the high-molecular-weight reader complex, resolving the architectural basis of multivalent ADP-ribose recognition.

    Evidence X-ray crystallography, native mass spectrometry, KO-cell reconstitution with deletion mutants

    PMID:38511494

    Open questions at the time
    • Full-length heterodimer structure remains unsolved
    • Oligomer regulation in cells is unknown
  12. 2024 High

    Identifying PARP14 as the major IFN-induced ADP-ribosyltransferase whose protein levels and activity are post-translationally regulated by the PARP9/DTX3L complex reframed DTX3L as a regulatory hub coordinating multiple PARP family members in interferon signaling.

    Evidence CRISPR KO, immunofluorescence of IFNγ-induced cytoplasmic inclusions, mass spectrometry, in vitro ADP-ribosylation assays with domain mutagenesis

    PMID:38182103 PMID:38834853

    Open questions at the time
    • Mechanism by which DTX3L/PARP9 stabilizes PARP14 protein is unresolved
    • Whether DTX3L ubiquitylates PARP14 directly is not demonstrated
  13. 2024 High

    Discovering that DTX3L ubiquitylates single-stranded DNA and RNA at the 3ʹ-terminal adenosine via ester bonds—an activity shared only with DTX3 among Deltex members and reversible by USP2, JOSD1, and SARS-CoV-2 PLpro—revealed an unprecedented nucleic acid-modifying function for a ubiquitin ligase.

    Evidence In vitro ubiquitylation with NMR structural analysis of DTC-ssDNA interaction, domain deletion, deubiquitinase cleavage assay, parallel family-wide comparison

    PMID:39242775 PMID:39377462

    Open questions at the time
    • Physiological role of nucleic acid ubiquitylation is completely unknown
    • Whether this occurs in cells or on specific transcripts/damage intermediates is untested
  14. 2024 High

    Showing that DTX3L ubiquitylates TIRR at K187 to promote its nuclear export and degradation, thereby displacing TIRR from 53BP1 and shifting DSB repair from NHEJ toward HR deficiency and PARP inhibitor sensitivity, defined a specific mechanism for DTX3L-mediated repair pathway regulation.

    Evidence Site-directed mutagenesis (K187), nuclear export inhibition, PARP inhibitor sensitivity assay, chromosomal instability analysis

    PMID:39632881

    Open questions at the time
    • Whether TIRR ubiquitylation is PARP9-dependent is not addressed
    • Relevance across tumor types beyond the tested lines is unclear
  15. 2025 High

    Demonstrating reciprocal enzymatic regulation between DTX3L and USP28—DTX3L ubiquitylates USP28 for degradation while USP28 deubiquitylates both itself and DTX3L—showed that a DTX3L/DUB axis fine-tunes all four major DSB repair pathways.

    Evidence Reciprocal ubiquitylation/deubiquitylation assays, DSB repair pathway reporter assays with double knockdown rescue

    PMID:40703443

    Open questions at the time
    • Whether this axis operates at damage sites or genome-wide is unknown
    • Upstream signals controlling the balance are not identified
  16. 2025 Medium

    Expanding the substrate repertoire in cancer contexts to include EGFR stabilization, SNAI1 degradation in EMT, SATB2 degradation in glioma stemness, LATS2 degradation in renal carcinoma, and PKCα degradation in breast cancer underscored DTX3L as a broadly relevant oncogenic or tumor-suppressive E3 ligase depending on context.

    Evidence Co-IP, ubiquitylation assays with site-directed mutagenesis, orthotopic/xenograft tumor models across multiple cancer types

    PMID:37460862 PMID:41203184 PMID:41507172 PMID:41679478 PMID:41972409

    Open questions at the time
    • Context-dependent pro- vs. anti-tumorigenic roles are not mechanistically reconciled
    • Whether PARP9 participates in all cancer-associated substrate ubiquitylation events is unknown
    • Most substrates validated by single labs

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological function of DTX3L-mediated nucleic acid ubiquitylation, the full structure of the oligomeric DTX3L-PARP9 complex, and the mechanism by which DTX3L chooses among its many protein substrates versus nucleic acid substrates in vivo remain unresolved.
  • No in vivo evidence for nucleic acid ubiquitylation
  • No full-length DTX3L-PARP9 structure
  • Substrate selectivity determinants unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 16 GO:0016874 ligase activity 8 GO:0042393 histone binding 2 GO:0140097 catalytic activity, acting on DNA 2 GO:0140098 catalytic activity, acting on RNA 2 GO:0016740 transferase activity 1
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 3 GO:0005829 cytosol 3
Pathway
R-HSA-392499 Metabolism of proteins 8 R-HSA-73894 DNA Repair 6 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 1
Partners
EGFRPARP14PARP9SRCSTAT1TBK1TIRRUSP28
Complex memberships
DTX3L-PARP9-PARP14 ternary complexPARP9-DTX3L heterodimer

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 DTX3L (BBAP) functions as an E3 ubiquitin ligase, demonstrated by self-ubiquitination activity; DTX family members homodimerize and heterodimerize in vivo, with BBAP and DTX1 associating via their unique N termini to enhance self-ubiquitination. In vitro self-ubiquitination assay, co-immunoprecipitation The Journal of biological chemistry High 12670957
2006 BBAP (DTX3L) regulates the subcellular localization of BAL1 (PARP9) through a dynamic shuttling mechanism, and both are regulated by a IFN-γ-responsive bidirectional promoter on chromosome 3q21. Immunofluorescence localization, reporter assay, co-expression studies Molecular and cellular biology Medium 16809771
2009 BBAP (DTX3L) selectively monoubiquitylates histone H4 at lysine 91, and disruption of this activity is associated with loss of chromatin-associated H4K20 methylase, reduction in mono- and dimethyl H4K20, and delayed 53BP1 foci formation at DNA damage sites. In vitro ubiquitylation assay, site-directed mutagenesis, immunofluorescence of 53BP1 foci Molecular cell High 19818714
2012 BAL1 (PARP9) is recruited to PARP1-PARylated DNA damage sites via its macrodomains in a PAR-dependent manner, and its partner DTX3L (BBAP) mediates local ubiquitylation that promotes subsequent BRCA1 and 53BP1 recruitment, functioning independently of ATM, MDC1, and RNF8. Genetic epistasis (ATM/MDC1/RNF8 knockouts), live-cell imaging, co-immunoprecipitation, PAR-binding assay Molecular and cellular biology High 23230272
2014 DTX3L forms a complex with ARTD8 (PARP14) and ARTD9 (PARP9), and together these complexes repress IRF1 expression; DTX3L together with STAT1 and STAT3 mediates cell migration; ARTD8 enzymatic activity is required for survival in metastatic prostate cancer cells. Co-immunoprecipitation, siRNA knockdown with proliferation/survival/migration assays, Western blot Molecular cancer Medium 24886089
2015 PARP9-DTX3L complex interacts with STAT1 and acts as an E3 ubiquitin ligase targeting host histone H2BJ to promote interferon-stimulated gene expression, and also targets viral 3C proteases for degradation via the immunoproteasome. Co-immunoprecipitation, transgenic mouse model, ubiquitin ligase assay, antiviral infection assay Nature immunology High 26479788
2015 DTX3L depletion in melanoma cells decreases FAK/PI3K/AKT signaling activity but not MEK/ERK signaling, and reduces invasion and metastasis, establishing FAK/PI3K/AKT as the pathway through which DTX3L mediates melanoma metastasis. siRNA knockdown, invasion/metastasis assays, Western blot of signaling intermediates Oncotarget Medium 26033450
2015 HDAC1,2 inhibition increases H4K91 acetylation, which competitively reduces BBAP (DTX3L)-mediated H4K91 monoubiquitination and impairs BBAP-dependent DSB repair. Small molecule inhibition, histone modification ChIP/Western blot, DSB repair assay Oncotarget Medium 25605023
2016 BBAP (DTX3L) translocates from the cytoplasm to the nucleus upon paclitaxel treatment in vemurafenib-resistant melanoma cells, and this translocation decreases metastatic ability via downregulation of phospho-FAK and N-cadherin and upregulation of p21 and E-cadherin. Immunofluorescence, subcellular fractionation, invasion/migration assays Molecular medicine reports Low 27922665
2017 DTX3L (PARP9/Dtx3L heterodimer) mediates NAD+-dependent mono-ADP-ribosylation of the carboxyl group of ubiquitin Gly76, exclusively in the context of ubiquitin processing by E1 and E2 enzymes; this ADP-ribosylation precludes substrate ubiquitylation. Poly(ADP-ribose) binding to PARP9 macrodomains increases E3 activity, while NAD+ restrains it. In vitro ADP-ribosylation assay, mutagenesis of NAD+ binding site, mass spectrometry, biochemical reconstitution Molecular cell High 28525742
2020 DTX3L and ARTD9 (PARP9) associate with STAT1 under TNF-α stimulation in fibroblast-like synoviocytes and modulate STAT1 nuclear localization and transcriptional activity, promoting expression of MMP-9 and IL-6. Co-immunoprecipitation, immunofluorescence, siRNA knockdown, Western blot Tissue & cell Low 32473705
2021 IFN signaling induces PARP9/DTX3L-dependent ADP-ribosylation of host proteins, and the SARS-CoV-2 Nsp3 macrodomain reverses this modification; however, deletion of PARP9 or DTX3L does not impair IFN signaling or induction of IFN-responsive genes, indicating ADP-ribosylation is a downstream effector rather than a signaling regulator. Immunofluorescence-based ADP-ribosylation assay, CRISPR knockout of PARP9/DTX3L, ectopic Nsp3 expression The Journal of biological chemistry High 34358560
2022 The DTX3L D3 domain (residues 230-510) mediates interaction with PARP9 with nanomolar affinity and 1:1 stoichiometry; the N-terminal region (1-200) mediates higher-order oligomerization; ADP-ribosylation of ubiquitin Gly76 is reversible in vitro by macrodomain-type hydrolases. Recombinant protein reconstitution, binding affinity measurement, size-exclusion chromatography, in vitro deribosylation assay The Biochemical journal High 35037691
2023 DTX3L rapidly co-localizes with p53 at PARP1-PARylated DNA damage sites, polyubiquitylates p53 on its lysine-rich C-terminal domain, and targets p53 for proteasomal degradation; DTX3L knockout significantly increases and prolongs p53 retention at damage sites. Co-immunoprecipitation, ubiquitylation assay, live-cell imaging, CRISPR knockout iScience High 37096048
2023 DTX3L ubiquitinates TBK1 at K30 and K401 via K63-linked ubiquitination, and binds SRC tyrosine kinase to mediate TBK1 phosphorylation, establishing an IFN-β-ETS1-DTX3L-TBK1 positive-feedback loop. Co-immunoprecipitation, site-directed mutagenesis of ubiquitination sites, kinase phosphorylation assay Journal of virology Medium 37255478
2023 DTX3L ubiquitinates NLRP3 via interaction between the NLRP3 LRR domain and the DTX3L RING domain, resulting in NLRP3 degradation and regulation of pyroptosis. Co-immunoprecipitation, mass spectrometry, domain mapping, ubiquitylation assay, LDH/cell death assays Biochimica et biophysica acta. Molecular cell research Medium 36706922
2023 Dual ADP-ribosylation of closely spaced cysteines on the androgen receptor (AR) by PARP7 mediates recognition by the DTX3L/PARP9 complex with high affinity (Kd = 80.5 nM); oligomerization of the DTX3L/PARP9 complex is required for efficient ADP-ribosyl-peptide interaction. Synthetic peptide binding assay, fluorescence-based affinity measurement, deletion mutagenesis of oligomerization domain ACS chemical biology High 37939374
2023 DTX3L mediates ubiquitination and degradation of cGAS in pancreatic cancer cells, suppressing cGAS-STING pathway activation and antitumor immunity. Co-immunoprecipitation, ubiquitylation assay, siRNA knockdown with STING pathway readout Biochemical and biophysical research communications Medium 37774567
2024 Crystal structure of the DTX3L N-terminal D2 domain reveals a tetramer with D2 symmetry and two interfaces; D1-D2 domains mediate homo-oligomerization and are dispensable for PARP9 heterodimerization but required for assembling the high-molecular-weight oligomeric complex with efficient reader function for ADP-ribosylated androgen receptor. X-ray crystallography, native mass spectrometry, DTX3L-KO cell reconstitution with deletion mutants, ADP-ribose reader assay Protein science High 38511494
2024 PARP14 is the major enzyme responsible for IFN-induced ADP-ribosylation; PARP9/DTX3L complex regulates PARP14 protein levels post-translationally and both localize to IFNγ-induced cytoplasmic inclusions; PARP14 ADP-ribosylates itself and DTX3L; PARP9 macrodomain 1 hydrolyzes PARP14 activity product. CRISPR knockout, immunofluorescence, mass spectrometry, in vitro ADP-ribosylation assay The EMBO journal High 38834853
2024 PARP9/DTX3L complex is required to uphold PARP14 protein levels via post-translational mechanisms; KH-like domains in PARP9, DTX3L, and PARP14 coordinate protein-protein interactions; DTX3L interaction with PARP14 in vitro suppresses PARP14 auto-ADP-ribosylation and promotes trans-ADP-ribosylation of PARP9 and DTX3L; DTX3L homodimerization is coordinated by a KH-like domain. In vitro ADP-ribosylation assay, domain mutagenesis, co-immunoprecipitation, cell survival assay with truncation mutants Journal of molecular biology High 38182103
2024 DTX3L ubiquitylates single-stranded DNA and RNA (and double-stranded DNA with ≥2 nt 3' overhang) via ester bond formation at the 3'-terminal adenosine; the minimal catalytic fragment comprises the C-terminal RING and DTC domains; NMR analysis shows the DTC domain binds single-stranded DNA and facilitates Ub transfer from RING-bound E2-conjugated Ub; this modification is reversibly cleaved by deubiquitinases including USP2, JOSD1, and SARS-CoV-2 PLpro. In vitro ubiquitylation assay, NMR, domain deletion mutagenesis, deubiquitinase cleavage assay eLife High 39377462
2024 DTX3L ubiquitylates DNA and RNA in vitro via ester bond formation; this activity is shared with DTX3 but not DTX1, DTX2, or DTX4; DTX3L shows preference for 3'-terminal adenosine; ubiquitylation of nucleic acids is reversible by USP2, JOSD1, and SARS-CoV-2 PLpro. In vitro ubiquitylation assay with purified proteins and synthetic substrates, parallel testing of all DELTEX family members EMBO reports High 39242775
2024 DTX3L ubiquitinates TIRR at lysine 187, facilitating XPO1-mediated TIRR nuclear export and proteasomal degradation after DNA damage; this displaces TIRR from 53BP1, impairing NHEJ and causing HR deficiency and PARP inhibitor sensitivity. Co-immunoprecipitation, site-directed mutagenesis (K187), nuclear export inhibition, PARP inhibitor sensitivity assay, chromosomal instability assay Nature communications High 39632881
2025 DTX3L ubiquitinates USP28, leading to its proteasomal degradation, while USP28 counteracts by deubiquitinating both itself and DTX3L; this mutual regulation fine-tunes DSB repair across NHEJ, HR, SSA, and MMEJ pathways. Ubiquitylation assay, deubiquitylation assay, DSB repair pathway reporter assays, double knockdown rescue iScience High 40703443
2023 DTX3L binds EGFR and prevents its ubiquitination-mediated degradation, thereby activating the FAK/PI3K/Akt pathway to promote pancreatic cancer progression. Co-immunoprecipitation, ubiquitylation assay, orthotopic tumor model, proliferation/invasion assays Biochemical genetics Medium 37460862
2026 DTX3L directly interacts with and ubiquitinates SNAI1 (SNAIL), a master EMT regulator, leading to GSK-3β-dependent proteasomal degradation of SNAI1; loss of DTX3L stabilizes SNAI1 and enhances EMT and stem-like phenotypes in gastric cancer. Co-immunoprecipitation, ubiquitylation assay, cell line/organoid/animal model, TGF-β1/miR-135b-5p regulatory axis characterization Advanced science Medium 41972409
2026 USP10 and DTX3L regulate SATB2 ubiquitination at K266 in glioma stem cells through mutually exclusive interactions and opposing activities; DTX3L acts as a ubiquitin ligase for SATB2, promoting its degradation. Co-immunoprecipitation, ubiquitylation assay, site-directed mutagenesis (K266), GSC self-renewal assay, in vivo tumor model Nature communications Medium 41507172
2026 DTX3L binds PKCα through its RING domain and targets PKCα for K48-linked ubiquitination and proteasomal degradation, attenuating p38 MAPK phosphorylation to drive breast cancer progression. Co-immunoprecipitation, domain mapping, ubiquitylation assay, transcriptomics after KD, kinase phosphorylation assay International journal of biological macromolecules Medium 41679478
2025 DTX3L promotes renal cell carcinoma progression by ubiquitinating and degrading the Hippo pathway tumor suppressor LATS2. Proteomic screening, co-immunoprecipitation, ubiquitylation assay, in vitro and in vivo tumor growth assays Cellular signalling Medium 41203184

Source papers

Stage 0 corpus · 47 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection. Nature immunology 185 26479788
2017 Ubiquitin Modification by the E3 Ligase/ADP-Ribosyltransferase Dtx3L/Parp9. Molecular cell 173 28525742
2009 BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response. Molecular cell 137 19818714
2003 The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity. The Journal of biological chemistry 125 12670957
2006 BAL1 and BBAP are regulated by a gamma interferon-responsive bidirectional promoter and are overexpressed in diffuse large B-cell lymphomas with a prominent inflammatory infiltrate. Molecular and cellular biology 103 16809771
2012 BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) activation, ubiquitylation, and double-strand DNA repair independent of ATM, MDC1, and RNF8. Molecular and cellular biology 97 23230272
2014 DTX3L and ARTD9 inhibit IRF1 expression and mediate in cooperation with ARTD8 survival and proliferation of metastatic prostate cancer cells. Molecular cancer 95 24886089
2021 The SARS-CoV-2 Nsp3 macrodomain reverses PARP9/DTX3L-dependent ADP-ribosylation induced by interferon signaling. The Journal of biological chemistry 92 34358560
2015 Deltex-3-like (DTX3L) stimulates metastasis of melanoma through FAK/PI3K/AKT but not MEK/ERK pathway. Oncotarget 49 26033450
2024 PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation. The EMBO journal 36 38834853
2015 HDAC1,2 inhibition impairs EZH2- and BBAP-mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma. Oncotarget 36 25605023
2023 DTX3L induced NLRP3 ubiquitination inhibit R28 cell pyroptosis in OGD/R injury. Biochimica et biophysica acta. Molecular cell research 31 36706922
2022 Reconstitution of the DTX3L-PARP9 complex reveals determinants for high-affinity heterodimerization and multimeric assembly. The Biochemical journal 28 35037691
2017 DTX3L is upregulated in glioma and is associated with glioma progression. International journal of molecular medicine 25 28627634
2024 PARP14 is regulated by the PARP9/DTX3L complex and promotes interferon γ-induced ADP-ribosylation. The EMBO journal 24 38834852
2024 KH-like Domains in PARP9/DTX3L and PARP14 Coordinate Protein-Protein Interactions to Promote Cancer Cell Survival. Journal of molecular biology 23 38182103
2022 Activities and binding partners of E3 ubiquitin ligase DTX3L and its roles in cancer. Biochemical Society transactions 20 36421918
2024 Ubiquitylation of nucleic acids by DELTEX ubiquitin E3 ligase DTX3L. EMBO reports 19 39242775
2024 Spatial transcriptome profiling identifies DTX3L and BST2 as key biomarkers in esophageal squamous cell carcinoma tumorigenesis. Genome medicine 19 39696540
2024 DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife 18 39377462
2018 Chemical activation of prolyl hydroxylase-2 by BBAP-1 down regulates hypoxia inducible factor-1α and fatty acid synthase for mammary gland chemoprevention. RSC advances 18 35541235
2023 DTX3L E3 ligase targets p53 for degradation at poly ADP-ribose polymerase-associated DNA damage sites. iScience 17 37096048
2023 Silencing DTX3L Inhibits the Progression of Cervical Carcinoma by Regulating PI3K/AKT/mTOR Signaling Pathway. International journal of molecular sciences 16 36614304
2023 Circular RNA circEYA3 promotes the radiation resistance of hepatocellular carcinoma via the IGF2BP2/DTX3L axis. Cancer cell international 16 38042777
2023 DTX3L Enhances Type I Interferon Antiviral Response by Promoting the Ubiquitination and Phosphorylation of TBK1. Journal of virology 15 37255478
2017 Effects of DTX3L on the cell proliferation, adhesion, and drug resistance of multiple myeloma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 14 28653881
2023 DTX3L Accelerates Pancreatic cancer Progression via FAK/PI3K/AKT Axis. Biochemical genetics 12 37460862
2023 Synthetic Dual Cysteine-ADP Ribosylated Peptides from the Androgen Receptor are Recognized by the DTX3L/PARP9 Complex. ACS chemical biology 12 37939374
2023 DTX3L mediated ubiquitination of cGAS suppresses antitumor immunity in pancreatic cancer. Biochemical and biophysical research communications 10 37774567
2024 Oligomerization mediated by the D2 domain of DTX3L is critical for DTX3L-PARP9 reading function of mono-ADP-ribosylated androgen receptor. Protein science : a publication of the Protein Society 7 38511494
2024 DTX3L-mediated TIRR nuclear export and degradation regulates DNA repair pathway choice and PARP inhibitor sensitivity. Nature communications 6 39632881
2016 Translocation of BBAP from the cytoplasm to the nucleus reduces the metastatic ability of vemurafenib-resistant SKMEL28 cells. Molecular medicine reports 5 27922665
2025 Small extracellular vesicles from adipose derived stem cells alleviate microglia activation and improve motor deficit of Parkinson's disease via miR-100-5p/DTX3L/STAT1 signaling axis. Experimental neurology 3 40194649
2025 DTX3L E3 ligase: Molecular functions, regulatory mechanisms, and potential as a novel cancer biomarker and therapeutic target. International journal of biological macromolecules 3 40695431
2020 DTX3L/ARTD9 contributes to inflammation of fibroblast-like synoviocytes by increasing STAT1 translocation. Tissue & cell 3 32473705
2025 The E3 ubiquitin ligase DTX3L and the deubiquitinase USP28 fine-tune DNA repair through mutual regulation of their protein levels. iScience 2 40703443
2023 Oligomerisation mediated by the D2 domain of DTX3L is critical for DTX3L-PARP9 reading function of mono-ADP-ribosylated androgen receptor. bioRxiv : the preprint server for biology 2 38076829
2024 Erratum: DTX3L E3 ligase targets p53 for degradation at poly ADP-ribose polymerase-associated DNA damage sites. iScience 1 39055911
2023 Discovery of DTX3L inhibitors through a homogeneous FRET-based assay that monitors formation and removal of poly-ubiquitin chains. SLAS discovery : advancing life sciences R & D 1 37579950
2026 USP10 promotes glioma stem cell maintenance and glioblastoma growth by antagonizing DTX3L-mediated SATB2 ubiquitination. Nature communications 0 41507172
2026 E3 ubiquitin ligase DTX3L promotes breast cancer progression by enhancing PKCα ubiquitination and inhibiting the p38 MAPK signaling pathway. International journal of biological macromolecules 0 41679478
2026 LINC00973/DTX3L Axis Promotes Non-Small Cell Lung Cancer Progression and Serves as a Therapeutic Target. Smart medicine 0 41684454
2026 Role of the H19/miR-423-5p/DTX3L Axis in Enhancing the Malignant Phenotype of Nasopharyngeal Carcinoma Cells. Biological & pharmaceutical bulletin 0 41882821
2026 Investigating the functions and molecular mechanisms of DTX3L in cancer progression. Frontiers in oncology 0 41883974
2026 [Expression of Concern] DTX3L is upregulated in glioma and is associated with glioma progression. International journal of molecular medicine 0 41930575
2026 DTX3L Inhibits the EMT, Metastasis, and Stem-Like Features of Gastric Cancer Through Promoting GSK-3β Dependent SNAI1 Decay. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41972409
2025 DTX3L promotes renal cell carcinoma progression via ubiquitination and degradation of LATS2. Cellular signalling 0 41203184