Affinage

DTX3L

E3 ubiquitin-protein ligase DTX3L · UniProt Q8TDB6

Length
740 aa
Mass
83.6 kDa
Annotated
2026-06-09
49 papers in source corpus 31 papers cited in narrative 29 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

DTX3L (BBAP) is a RING-type E3 ubiquitin ligase that operates as the catalytic engine of an obligate heterodimer with the macrodomain protein PARP9, coordinating protein ubiquitylation, ADP-ribosylation, and the DNA damage response (PMID:12670957, PMID:23230272, PMID:28525742). DTX3L homo-oligomerizes through an N-terminal D1–D2 region — its D2 domain crystallizes as a tetramer — while binding PARP9 with nanomolar affinity through a distinct D3 domain; oligomerization is dispensable for heterodimer formation but required for efficient reading of ADP-ribosylated substrates such as the androgen receptor (PMID:35037691, PMID:37939374, PMID:38511494). The complex carries two opposing enzymatic outputs: classical E3 ligase activity and a PARP9-dependent NAD+-driven mono-ADP-ribosylation of ubiquitin's C-terminal Gly76 that competitively blocks substrate ubiquitylation, a modification reversible by macrodomain hydrolases (PMID:28525742, PMID:35037691). In the DNA damage response, DTX3L-PARP9 is recruited to PARP1-PARylated lesions independently of the ATM/MDC1/RNF8 axis, where DTX3L monoubiquitylates histone H4 at K91 to promote 53BP1 and BRCA1 recruitment, and additionally polyubiquitylates p53 for proteasomal degradation at damage sites (PMID:19818714, PMID:23230272, PMID:37096048). DTX3L further tunes repair pathway choice by ubiquitylating TIRR (K187) to release 53BP1 and by reciprocally antagonizing the deubiquitinase USP28 (PMID:39632881, PMID:40703443). In immunity, the PARP9-DTX3L complex ubiquitylates histone H2BJ to drive interferon-stimulated gene expression and degrades viral 3C proteases, amplifies type I interferon signaling by K63-ubiquitylating TBK1, and functions as a downstream effector of PARP14-driven IFN-induced ADP-ribosylation (PMID:26479788, PMID:37255478, PMID:38834853, PMID:38834852). Beyond protein targets, DTX3L directly ubiquitylates single-stranded DNA and RNA at their 3' ends via its C-terminal RING-DTC domains through ester bond formation (PMID:39377462, PMID:39242775). Across multiple cancers, DTX3L ubiquitylates a broad substrate set — including SATB2, SNAI1, LATS2, PKCα, and NLRP3, and stabilizes EGFR — to modulate proliferation, EMT, and signaling (PMID:36706922, PMID:37460862, PMID:41507172, PMID:41972409, PMID:41679478).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2003 High

    Established that DTX3L is an active E3 ubiquitin ligase that dimerizes, answering whether the protein had intrinsic catalytic function and how it assembles.

    Evidence In vitro self-ubiquitination assay, yeast two-hybrid, and co-IP showing homo- and heterodimerization with DTX1

    PMID:12670957

    Open questions at the time
    • No physiological substrate identified
    • PARP9 partnership not yet known
  2. 2006 Medium

    Linked DTX3L to PARP9 (BAL1) by showing it controls the partner's subcellular shuttling, establishing the functional interdependence later defined as obligate heterodimerization.

    Evidence Subcellular fractionation and fluorescence microscopy of dynamic shuttling

    PMID:16809771

    Open questions at the time
    • Interaction interface not mapped
    • Enzymatic consequence of partnership undefined
  3. 2009 High

    Identified histone H4K91 as a specific DTX3L substrate and connected this monoubiquitylation to 53BP1 recruitment, defining a chromatin role in the DNA damage response.

    Evidence In vitro ubiquitination, site mutagenesis, ChIP, and 53BP1 foci immunofluorescence

    PMID:19818714

    Open questions at the time
    • Recruitment mechanism to damage sites not defined
    • Relationship to canonical DDR ligases unresolved
  4. 2012 High

    Placed DTX3L-PARP9 in an ATM/MDC1/RNF8-independent DDR branch recruited via PARP1 PARylation, resolving where the pathway sits relative to canonical signaling.

    Evidence Genetic epistasis with knockouts, laser-stripe damage live imaging, co-IP, ubiquitylation assays

    PMID:23230272

    Open questions at the time
    • Direct PAR-binding determinant of recruitment within complex not isolated here
    • Full substrate repertoire at lesions unknown
  5. 2015 High

    Defined dual immune effector roles: histone H2BJ ubiquitylation to promote ISG expression and degradation of viral 3C proteases, establishing the complex as an antiviral effector.

    Evidence Co-IP, in vitro ubiquitination, STAT1 variant cells, transgenic mouse, viral infection assays

    PMID:26479788

    Open questions at the time
    • Mechanism of STAT1 cooperation not fully resolved
    • Substrate selectivity rules undefined
  6. 2017 High

    Discovered NAD+-dependent ADP-ribosylation of ubiquitin Gly76 by the heterodimer, revealing an autoregulatory switch that competitively inhibits the ligase's own activity.

    Evidence Reconstituted ubiquitin processing assay, MS site mapping, mutagenesis, NAD+ titration

    PMID:28525742

    Open questions at the time
    • In vivo regulatory significance of the switch not established
    • Spatial/temporal control of the two activities unclear
  7. 2021 High

    Clarified that PARP9/DTX3L-dependent IFN-induced ADP-ribosylation is a downstream effector rather than a mediator of IFN signaling, and is reversed by SARS-CoV-2 Nsp3 macrodomain.

    Evidence Immunofluorescence ADP-ribosylation assay, PARP9/DTX3L knockout cells, Nsp3 ectopic expression

    PMID:34358560

    Open questions at the time
    • Identity of the relevant transferase not yet resolved here
    • Functional consequence of the modified targets unknown
  8. 2022 High

    Mapped the modular architecture — D3 domain for nanomolar 1:1 PARP9 binding, N-terminal region for oligomerization — and showed ubiquitin-Gly76 ADP-ribosylation is reversible by macrodomain hydrolases.

    Evidence Recombinant protein binding affinity, SEC, in vitro reversal assays

    PMID:35037691

    Open questions at the time
    • Functional role of oligomerization not yet demonstrated
    • Structural basis of assembly not resolved
  9. 2023 High

    Demonstrated DTX3L polyubiquitylates p53 at PARylated damage sites to limit its retention, defining a feedback control on DDR signaling intensity.

    Evidence Reciprocal co-IP, ubiquitination assay, DTX3L knockout cells, proteasome inhibition, immunofluorescence

    PMID:37096048

    Open questions at the time
    • Physiological outcome on p53 transcriptional programs unaddressed
    • Linkage chain type on p53 not specified
  10. 2023 Medium

    Expanded the substrate set to immune and signaling regulators — NLRP3, TBK1, cGAS, EGFR — defining DTX3L as a node controlling inflammasome, interferon, and growth-factor pathways.

    Evidence Co-IP, domain mapping, site-specific ubiquitination (TBK1 K30/K401), functional pyroptosis/IFN/tumor readouts

    PMID:36706922 PMID:37255478 PMID:37460862 PMID:37774567

    Open questions at the time
    • Most substrates from single labs without reciprocal cross-validation
    • Context-dependence (degradative vs signaling) of each substrate unresolved
  11. 2023 High

    Showed dual ADP-ribosylation of closely spaced cysteines generates a high-affinity reader site requiring DTX3L oligomerization, linking oligomeric assembly to substrate recognition.

    Evidence Synthetic peptide chemistry, fluorescence binding, oligomerization mutant analysis

    PMID:37939374

    Open questions at the time
    • Downstream fate of the recognized androgen receptor not detailed
    • Generality of the dual-modification readout for other substrates untested
  12. 2024 High

    Resolved the structural basis of oligomerization (D2 tetramer crystal structure) and mapped KH-like domains mediating PARP9/PARP14/DTX3L interactions, connecting assembly to reader function and ADP-ribosylation regulation.

    Evidence X-ray crystallography, native MS, KO reconstitution with D1-D2 deletion, in vitro binding and mutagenesis

    PMID:38182103 PMID:38511494

    Open questions at the time
    • Stoichiometry of the full multi-protein assembly in cells unresolved
    • Regulation of oligomeric state in vivo unknown
  13. 2024 High

    Identified PARP14 as the major IFN-induced transferase whose levels and activity are regulated by PARP9/DTX3L, defining the upstream-effector relationship in IFN ADP-ribosylation.

    Evidence Improved MAR antibody detection, PARP14/PARP9/DTX3L KO cells, co-localization imaging, biochemical assays

    PMID:38834852 PMID:38834853

    Open questions at the time
    • Functional outcome of cytoplasmic inclusion formation unclear
    • Targets of PARP14 modification relevant to antiviral defense not enumerated
  14. 2024 High

    Revealed direct ubiquitylation of single-stranded nucleic acids at 3' ends by the RING-DTC module, establishing a non-protein substrate class for the ligase.

    Evidence In vitro ubiquitination with DNA/RNA substrates, NMR, domain truncation, DUB reversal, DTX family comparison

    PMID:39242775 PMID:39377462

    Open questions at the time
    • Cellular function of nucleic-acid ubiquitylation unknown
    • In vivo substrates and biological pathway unestablished
  15. 2024 High

    Showed DTX3L ubiquitylates TIRR (K187) to drive its nuclear export and degradation, releasing 53BP1 and biasing repair toward NHEJ with PARP-inhibitor sensitization.

    Evidence Co-IP, K187 site mapping, XPO1 inhibition, overexpression/knockdown, PARP inhibitor sensitivity

    PMID:39632881

    Open questions at the time
    • Integration with the H4K91/p53 DDR functions not unified
    • Trigger linking damage to TIRR ubiquitylation unspecified
  16. 2025 High

    Established reciprocal antagonism between DTX3L and USP28 that fine-tunes choice across multiple DSB repair pathways, adding a deubiquitinase counterweight to DTX3L control of repair.

    Evidence Reciprocal co-IP, ubiquitination/deubiquitination assays, knockdown epistasis rescue, repair pathway reporters

    PMID:40703443

    Open questions at the time
    • Stoichiometric balance setting the switch unknown
    • Whether this acts at chromatin or globally unresolved
  17. 2025 High

    Extended DTX3L's degradative substrate range in cancer to SATB2 (K266) and LATS2, with competing deubiquitinase USP10 for SATB2, linking DTX3L to glioma stemness and Hippo signaling.

    Evidence Co-IP, site-specific ubiquitination, competing-enzyme analysis, rescue, in vivo tumor models

    PMID:41203184 PMID:41507172

    Open questions at the time
    • GSK-3β dependence mechanism not fully dissected
    • Tissue specificity of substrate selection unexplained
  18. 2026 Medium

    Added SNAI1 and PKCα as degradative substrates controlling EMT and MAPK signaling, with upstream miRNA regulation of DTX3L itself, broadening its role in metastasis suppression and progression.

    Evidence Co-IP, ubiquitination assays (K48-linkage for PKCα), miR-135b-5p manipulation, organoid and animal models

    PMID:41679478 PMID:41972409

    Open questions at the time
    • Single-lab findings without reciprocal validation
    • Reconciliation of pro- and anti-tumor roles across tissues unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DTX3L selects among its many protein and nucleic-acid substrates, and how the competing ubiquitylation and ubiquitin-ADP-ribosylation activities are spatially and temporally partitioned in cells, remains unresolved.
  • No unifying model for substrate selectivity
  • In vivo regulation of the ligase-vs-ADP-ribosyltransferase switch undefined
  • Function of nucleic-acid ubiquitylation in cells unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016874 ligase activity 3 GO:0016740 transferase activity 2 GO:0042393 histone binding 2 GO:0003677 DNA binding 1 GO:0003723 RNA binding 1 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-73894 DNA Repair 5 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 2
Partners
DTX1EGFRPARP14PARP9STAT1TBK1TIRRUSP28
Complex memberships
DTX3L-PARP9 heterodimerDTX3L-PARP9-PARP14 complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 BBAP (DTX3L) functions as an E3 ubiquitin ligase capable of self-ubiquitination; it homodimerizes and heterodimerizes with DTX family members (DTX1) via unique N-termini, and heterodimerization with DTX1 enhances self-ubiquitination activity. In vitro ubiquitination assay (self-ubiquitination), yeast two-hybrid screen, in vivo co-immunoprecipitation The Journal of biological chemistry High 12670957
2006 BBAP (DTX3L) regulates the subcellular localization of its binding partner BAL1 (PARP9) through a dynamic shuttling mechanism, establishing a functional requirement for coordinated BBAP and BAL1 expression. Subcellular fractionation, fluorescence microscopy showing dynamic shuttling Molecular and cellular biology Medium 16809771
2009 BBAP (DTX3L) selectively monoubiquitylates histone H4 at lysine 91 (H4K91); disruption of this modification leads to loss of chromatin-associated H4K20 methylase, reduction of mono- and dimethyl H4K20, and delayed 53BP1 foci formation at DNA damage sites. In vitro ubiquitination assay, site-specific mutagenesis, chromatin immunoprecipitation, immunofluorescence for 53BP1 foci Molecular cell High 19818714
2012 BAL1 (PARP9) macrodomain-containing protein and its partner BBAP (DTX3L) E3 ligase are recruited to DNA damage sites via PARP1-dependent PARylation; BBAP-mediated local ubiquitylation then promotes 53BP1 and BRCA1 recruitment; this DDR pathway operates independently of ATM, MDC1, and RNF8. Genetic epistasis (ATM/MDC1/RNF8 knockouts), laser-stripe DNA damage + live-cell imaging, co-immunoprecipitation, ubiquitylation assays Molecular and cellular biology High 23230272
2014 DTX3L forms a protein complex with ARTD8 (PARP14) and ARTD9 (PARP9); DTX3L together with ARTD9 act as repressors of IRF1 expression in metastatic prostate cancer cells, and DTX3L together with STAT1 and STAT3 is implicated in cell migration. Co-immunoprecipitation, RNA interference knockdown, immunofluorescence Molecular cancer Medium 24886089
2015 The PARP9-DTX3L complex acts as an E3 ubiquitin ligase that ubiquitylates host histone H2BJ to promote interferon-stimulated gene expression, and also targets viral 3C proteases for degradation via the immunoproteasome; the complex interacts with STAT1 to enhance interferon signaling. Co-immunoprecipitation, in vitro ubiquitination assay, transgenic mouse model, transduced human cells with STAT1 variant, viral infection assays Nature immunology High 26479788
2015 DTX3L (Dtx3l) promotes melanoma invasion and metastasis through the FAK/PI3K/AKT signaling pathway but not through MEK/ERK signaling; depletion of DTX3L decreased FAK/PI3K/AKT activity. siRNA knockdown, western blot for pathway components, invasion/migration assays, transgenic mouse melanoma model Oncotarget Medium 26033450
2015 HDAC1,2 inhibition increases H4K91 acetylation and decreases BBAP (DTX3L)-mediated H4K91 monoubiquitination, thereby impairing BBAP-dependent DSB repair; H4K91 is a shared substrate for both acetylation and BBAP-mediated ubiquitination. Pharmacological HDAC1,2 inhibition, western blot for H4K91 modifications, DNA damage repair assays Oncotarget Medium 25605023
2017 The DTX3L/PARP9 (Dtx3L/Parp9) heterodimer mediates NAD+-dependent mono-ADP-ribosylation of the C-terminal glycine 76 (Gly76) of ubiquitin exclusively in the context of ubiquitin processing by E1 and E2 enzymes; ADP-ribosylation of Ub Gly76 precludes ubiquitylation of substrates. PARP9 macrodomain binding to poly(ADP-ribose) increases E3 activity, and mutation of the NAD+ binding site in PARP9 increases DNA repair activity of the heterodimer. In vitro reconstituted ubiquitin processing assay, mass spectrometry for ADP-ribosylation site, site-directed mutagenesis, biochemical NAD+ titration Molecular cell High 28525742
2021 IFN-response-induced ADP-ribosylation of host proteins is dependent on PARP9 and its binding partner DTX3L; however, deletion of either PARP9 or DTX3L does not impair IFN signaling or induction of IFN-responsive genes, indicating that PARP9/DTX3L-dependent ADP-ribosylation is a downstream effector rather than a mediator of IFN signaling. The SARS-CoV-2 Nsp3 macrodomain reverses this IFN-induced ADP-ribosylation. Immunofluorescence-based ADP-ribosylation assay, PARP9/DTX3L knockout cell lines, ectopic expression of Nsp3 macrodomain 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 DTX3L N-terminal region (residues 1-200) mediates assembly into a higher-molecular-weight oligomer. ADP-ribosylation of ubiquitin at Gly76 by DTX3L-PARP9 is reversible in vitro by several macrodomain-type hydrolases. Recombinant protein production, binding affinity measurements, size exclusion chromatography, in vitro ADP-ribosylation reversal assays The Biochemical journal High 35037691
2023 During an initial DNA damage response, DTX3L rapidly co-localizes with p53 at PARP1-PARylated DNA damage sites, polyubiquitylates p53 at its lysine-rich C-terminal domain, and targets p53 for proteasomal degradation; DTX3L knockout significantly increases and prolongs p53 retention at these sites. Co-immunoprecipitation, ubiquitination assay, DTX3L knockout cells, immunofluorescence for p53 at damage sites, proteasome inhibitor experiments iScience High 37096048
2023 DTX3L ubiquitinates NLRP3 (interacting via the NLRP3 LRR domain and DTX3L RING domain), resulting in NLRP3 degradation and regulation of OGD/R-induced pyroptosis in R28 cells. Co-immunoprecipitation, mass spectrometry for interactors, domain-mapping experiments, ubiquitination assays, pyroptosis assays (LDH, staining) Biochimica et biophysica acta. Molecular cell research Medium 36706922
2023 DTX3L ubiquitinates TBK1 at K30 and K401 via K63-linked ubiquitination; DTX3L also binds the tyrosine kinase SRC and together they enhance TBK1 phosphorylation, forming a positive-feedback loop (IFN-β-ETS1-DTX3L-TBK1) that amplifies type I interferon antiviral responses. Co-immunoprecipitation, in vitro ubiquitination assay with site-specific mutagenesis (K30, K401), phosphorylation assays, reporter assays for IFN-β promoter activity Journal of virology Medium 37255478
2023 DTX3L mediates ubiquitination and degradation of cGAS, suppressing cGAS-STING pathway activation and antitumor immunity in pancreatic cancer cells. Co-immunoprecipitation, ubiquitination assay, DTX3L silencing with cGAS-STING pathway activation readout Biochemical and biophysical research communications Medium 37774567
2023 Dual ADP-ribosylation of closely spaced cysteines in the androgen receptor (AR) mediates high-affinity recognition by the DTX3L/PARP9 complex (Kd = 80.5 nM for dual vs. single ADP-ribosylated peptide); oligomerization of DTX3L/PARP9 is required for efficient ADP-ribosyl-peptide interaction. Synthetic peptide chemistry, fluorescence binding assays, oligomerization mutant analysis ACS chemical biology High 37939374
2023 DTX3L binds EGFR and prevents its ubiquitination-mediated degradation, leading to EGFR upregulation that activates the FAK/PI3K/Akt pathway to promote pancreatic cancer progression. Co-immunoprecipitation, ubiquitination assay, western blot for pathway activation, in vivo orthotopic tumor model Biochemical genetics Medium 37460862
2024 PARP14 is the major ADP-ribosyltransferase responsible for IFN-induced ADP-ribosylation; the PARP9/DTX3L complex regulates PARP14 protein levels via post-translational mechanisms and through PARP9 macrodomain 1 hydrolytic activity. PARP9/DTX3L and PARP14 co-localize to IFN-induced cytoplasmic inclusions, and DTX3L and PARP14 are themselves targets of PARP14 ADP-ribosylation. Interaction of DTX3L suppresses PARP14 auto-ADP-ribosylation and promotes trans-ADP-ribosylation of PARP9 and DTX3L. Improved mono-ADP-ribosylation antibody detection, PARP14/PARP9/DTX3L knockout cells, immunofluorescence co-localization, biochemical interaction assays The EMBO journal High 38834852 38834853
2024 KH-like domains in PARP9, DTX3L, and PARP14 mediate protein-protein interactions: PARP9-DTX3L and PARP14-DTX3L interactions are coordinated through KH-like domains, and DTX3L homodimerization is also coordinated by a KH-like domain and disrupted by site-specific mutation. DTX3L interaction in vitro suppresses PARP14 auto-ADP-ribosylation and promotes trans-ADP-ribosylation of PARP9 and DTX3L. In vitro binding assays, site-directed mutagenesis of KH-like domain, ADP-ribosylation activity assays, PARP14 truncation rescue experiments Journal of molecular biology Medium 38182103
2024 The DTX3L N-terminal D2 domain forms a tetramer with D2 symmetry (crystal structure resolved), containing a major interface of 973 Ų and a minor interface of 415 Ų; native MS confirms monomers, dimers, and tetramers. The D1-D2 region is dispensable for DTX3L-PARP9 heterodimer formation but required for oligomeric complex assembly and efficient reader function for ADP-ribosylated androgen receptor. X-ray crystallography, native mass spectrometry, DTX3L knockout cell reconstitution with D1-D2 deletion mutant, ADP-ribosyl binding assays Protein science : a publication of the Protein Society High 38511494
2024 DTX3L ubiquitinates single-stranded DNA and RNA (preferentially at the 3'-terminal adenosine), as well as double-stranded DNA with a 3' overhang of ≥2 nucleotides, via ester bond formation; the minimal catalytically competent fragment comprises the C-terminal RING and DTC domains (RD). NMR and biochemical analyses show the DTC domain binds single-stranded DNA and facilitates Ub transfer from RING-bound E2-Ub. This ubiquitylation is reversible by deubiquitinases (USP2, JOSD1, SARS-CoV-2 PLpro). This activity is shared with DTX3 but not DTX1, DTX2, or DTX4. In vitro ubiquitination assays with DNA/RNA substrates, NMR spectroscopy, domain truncation analysis, DUB reversal assays, comparative analysis across DTX family members eLife High 39242775 39377462
2024 DTX3L ubiquitinates TIRR at lysine 187, promoting XPO1-mediated nuclear export and proteasomal degradation of TIRR upon DNA damage; this releases 53BP1 from TIRR-mediated inhibition, altering DNA repair pathway choice toward NHEJ and increasing sensitivity to PARP inhibitors. Co-immunoprecipitation, ubiquitination assay with K187 site mapping, nuclear export inhibition (XPO1 inhibitor), DTX3L overexpression/knockdown, PARP inhibitor sensitivity assays Nature communications High 39632881
2025 DTX3L ubiquitinates USP28 leading to its proteasomal degradation; reciprocally, USP28 deubiquitinates both itself and DTX3L. This antagonistic cross-regulation fine-tunes DSB repair in NHEJ, HR, SSA, and MMEJ pathways; detrimental effects of USP28 depletion on DSB repair are rescued by concurrent DTX3L knockdown. Co-immunoprecipitation, ubiquitination assays, deubiquitination assays, siRNA knockdown epistasis, multiple DSB repair pathway reporters iScience High 40703443
2025 DTX3L acts as an E3 ubiquitin ligase for SATB2 in glioma stem cells, ubiquitinating SATB2 at K266 to promote its GSK-3β-dependent proteasomal degradation; USP10 opposes this by deubiquitinating SATB2 at the same residue via mutually exclusive interactions. DTX3L overexpression downregulates SATB2 and inhibits GSC self-renewal and GBM growth. Co-immunoprecipitation, ubiquitination assay with K266 site mapping, USP10/DTX3L overexpression/knockdown, rescue with SATB2 overexpression, in vivo tumor models Nature communications High 41507172
2025 DTX3L ubiquitinates LATS2 (a Hippo pathway tumor suppressor) to promote its degradation in renal cell carcinoma cells, activating downstream oncogenic signaling. Proteomic screening, co-immunoprecipitation, ubiquitination assay, in vitro and in vivo tumor growth assays Cellular signalling Medium 41203184
2026 DTX3L directly interacts with and ubiquitinates SNAI1, leading to its GSK-3β-dependent proteasomal degradation, thereby suppressing EMT and metastasis in gastric cancer; TGF-β1-induced miR-135b-5p downregulates DTX3L, stabilizing SNAI1 and enhancing EMT. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor experiments, miR-135b-5p manipulation, cell migration/invasion assays, organoid and animal models Advanced science Medium 41972409
2026 DTX3L binds PKCα through its RING domain and targets PKCα for K48-linked ubiquitination and proteasomal degradation, thereby attenuating p38 MAPK phosphorylation and driving breast cancer progression. Co-immunoprecipitation, ubiquitination assay with K48-linkage specification, RING domain binding analysis, transcriptomic profiling after DTX3L knockdown, western blot for p38 phosphorylation International journal of biological macromolecules Medium 41679478
2016 Translocation of BBAP (DTX3L) from the cytoplasm to the nucleus (induced by paclitaxel treatment) decreases the metastatic ability of vemurafenib-resistant melanoma cells, with downregulation of phospho-FAK and N-cadherin and upregulation of p21 and E-cadherin. Immunofluorescence for subcellular localization, migration/invasion assays, western blot for downstream markers Molecular medicine reports Low 27922665
2020 DTX3L and ARTD9 associate with STAT1 under TNF-α-stimulated conditions in fibroblast-like synoviocytes and modulate STAT1 nuclear localization and transcriptional activity, promoting MMP-9 and IL-6 expression. Co-immunoprecipitation, immunofluorescence for STAT1 nuclear localization, RNA interference knockdown, western blot Tissue & cell Low 32473705

Source papers

Stage 0 corpus · 49 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 187 26479788
2017 Ubiquitin Modification by the E3 Ligase/ADP-Ribosyltransferase Dtx3L/Parp9. Molecular cell 175 28525742
2009 BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response. Molecular cell 139 19818714
2003 The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity. The Journal of biological chemistry 127 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 106 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 99 23230272
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
2021 The SARS-CoV-2 Nsp3 macrodomain reverses PARP9/DTX3L-dependent ADP-ribosylation induced by interferon signaling. The Journal of biological chemistry 95 34358560
2015 Deltex-3-like (DTX3L) stimulates metastasis of melanoma through FAK/PI3K/AKT but not MEK/ERK pathway. Oncotarget 50 26033450
2024 PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation. The EMBO journal 43 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 37 25605023
2023 DTX3L induced NLRP3 ubiquitination inhibit R28 cell pyroptosis in OGD/R injury. Biochimica et biophysica acta. Molecular cell research 32 36706922
2024 PARP14 is regulated by the PARP9/DTX3L complex and promotes interferon γ-induced ADP-ribosylation. The EMBO journal 28 38834852
2022 Reconstitution of the DTX3L-PARP9 complex reveals determinants for high-affinity heterodimerization and multimeric assembly. The Biochemical journal 28 35037691
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 DTX3L is upregulated in glioma and is associated with glioma progression. International journal of molecular medicine 26 28627634
2024 Spatial transcriptome profiling identifies DTX3L and BST2 as key biomarkers in esophageal squamous cell carcinoma tumorigenesis. Genome medicine 23 39696540
2023 DTX3L E3 ligase targets p53 for degradation at poly ADP-ribose polymerase-associated DNA damage sites. iScience 21 37096048
2024 Ubiquitylation of nucleic acids by DELTEX ubiquitin E3 ligase DTX3L. EMBO reports 20 39242775
2024 DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife 20 39377462
2022 Activities and binding partners of E3 ubiquitin ligase DTX3L and its roles in cancer. Biochemical Society transactions 20 36421918
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 Silencing DTX3L Inhibits the Progression of Cervical Carcinoma by Regulating PI3K/AKT/mTOR Signaling Pathway. International journal of molecular sciences 17 36614304
2023 Circular RNA circEYA3 promotes the radiation resistance of hepatocellular carcinoma via the IGF2BP2/DTX3L axis. Cancer cell international 17 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 15 28653881
2023 DTX3L Accelerates Pancreatic cancer Progression via FAK/PI3K/AKT Axis. Biochemical genetics 14 37460862
2023 DTX3L mediated ubiquitination of cGAS suppresses antitumor immunity in pancreatic cancer. Biochemical and biophysical research communications 12 37774567
2023 Synthetic Dual Cysteine-ADP Ribosylated Peptides from the Androgen Receptor are Recognized by the DTX3L/PARP9 Complex. ACS chemical biology 12 37939374
2024 DTX3L-mediated TIRR nuclear export and degradation regulates DNA repair pathway choice and PARP inhibitor sensitivity. Nature communications 9 39632881
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
2016 Translocation of BBAP from the cytoplasm to the nucleus reduces the metastatic ability of vemurafenib-resistant SKMEL28 cells. Molecular medicine reports 6 27922665
2025 The E3 ubiquitin ligase DTX3L and the deubiquitinase USP28 fine-tune DNA repair through mutual regulation of their protein levels. iScience 4 40703443
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
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 2 37579950
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
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 promotes ovarian cancer progression and cisplatin resistance by activating JAK1/STAT1/OAS3 pathway. Scientific reports 0 41935138
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
2026 KLF14 restrained NLRP3-mediated pyroptosis in sepsis-induced acute lung injury by activating DTX3L. Central-European journal of immunology 0 42245128
2025 DTX3L promotes renal cell carcinoma progression via ubiquitination and degradation of LATS2. Cellular signalling 0 41203184

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