Affinage

RNF146

E3 ubiquitin-protein ligase RNF146 · UniProt Q9NTX7

Length
359 aa
Mass
39.0 kDa
Annotated
2026-06-10
38 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RNF146 is a RING-domain E3 ubiquitin ligase that couples tankyrase-dependent poly(ADP-ribosyl)ation (PARylation) to K48-linked polyubiquitination and proteasomal degradation, thereby acting as the destruction arm of the PARylation-dependent ubiquitination (PARdU) axis across Wnt/β-catenin, Hippo, innate immune, and cell-death signaling (PMID:21478859, PMID:21799911). Its WWE domain directly binds poly(ADP-ribose) and the smallest internal PAR unit, iso-ADP-ribose, which lodges between the WWE and RING domains and allosterically converts the catalytically inactive RING into an active E2-engaging state; in parallel, multiple noncanonical extended tankyrase-binding motifs in its C-terminus mediate weak-but-multivalent binding to the ankyrin repeats of TNKS1/2, recruiting RNF146 to PARylated substrates (PMID:25327252, PMID:29604130). Through this mechanism RNF146 forms a complex with tankyrase and ubiquitylates targets after they are PARylated by TNKS: it degrades Axin to promote Wnt/β-catenin signaling (PMID:21478859, PMID:21799911), angiomotin-family proteins to maintain the junctional Crumbs complex (PMID:27521426), PARylated VISA/MAVS to attenuate antiviral interferon induction (PMID:35733260), and activated RIPK1 within TAX1BP1-nucleated tankyrase/RNF146 condensates to restrain necroptosis (PMID:38272024). Substrate profiling in TNKS-double-knockout cells shows RNF146 also has tankyrase-independent substrates such as OTUD5 and PARP10 (PMID:32958691). RNF146 activity is further tuned by SUMOylation, which drives nuclear localization and accelerates Axin turnover (PMID:37029301), and its physiology is documented in vivo, where loss stabilizes Axin1 and 3BP2 to reprogram osteoclast/osteoblast development, glucose handling, and inflammatory responses (PMID:28287403, PMID:28581440). RNF146 additionally protects against PARP1-driven parthanatos by sequestering PAR polymer independently of its ligase activity (PMID:33443209).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2011 High

    Established RNF146 as the molecular bridge that converts tankyrase-dependent PARylation into ubiquitin-mediated degradation, answering how a PAR signal is read and translated into protein turnover.

    Evidence RNAi screening, Co-IP, proteomics, ubiquitylation and Wnt reporter assays identifying WWE-domain PAR binding and degradation of Axin, BLZF1, CASC3

    PMID:21478859 PMID:21799911

    Open questions at the time
    • Structural basis of PAR-induced activation not yet defined
    • Full substrate repertoire unknown
  2. 2014 High

    Resolved how PAR binding activates RNF146 — iso-ADP-ribose binding between WWE and RING domains allosterically licenses E2 engagement, and a C-terminal region directly binds tankyrase.

    Evidence X-ray crystallography with biochemical, mutagenesis, E2-binding, and cell-based Axin stability assays

    PMID:25327252

    Open questions at the time
    • Did not enumerate which substrates require allosteric activation versus tankyrase tethering
  3. 2018 High

    Defined the architecture of the RNF146–tankyrase interaction as multivalent binding through noncanonical extended tankyrase-binding motifs to TNKS ankyrin repeats.

    Evidence Crystal structure of a noncanonical TBM with TNKS ARD plus affinity assays and TBM mutagenesis

    PMID:29604130

    Open questions at the time
    • Stoichiometry and cooperativity within the full complex not fully resolved
  4. 2016 High

    Extended RNF146 function beyond Wnt by showing it degrades PARylated angiomotin proteins to maintain apical Crumbs/PALS1 polarity, linking the PARdU axis to junctional/Hippo biology.

    Evidence RNAi, reciprocal Co-IP, ubiquitylation assays, immunofluorescence, and epistatic rescue by AMOTL2 knockdown

    PMID:27521426

    Open questions at the time
    • Direct connection to downstream Hippo transcriptional output not measured
  5. 2017 High

    Demonstrated in vivo physiological roles by showing transcriptional repression of RNF146 and substrate stabilization (3BP2, Axin1) coordinate osteoclast/osteoblast programs, metabolism, and inflammatory responses.

    Evidence Promoter analysis, knockout mice, in vivo LPS challenge, Wnt reporter and substrate stability assays

    PMID:28287403 PMID:28581440

    Open questions at the time
    • Tissue-specific substrate priorities incompletely defined
  6. 2017 Medium

    Showed using vertebrate (Xenopus) and invertebrate (Drosophila) genetics that RNF146 is required for Wnt-dependent patterning and Axin proteolysis but is dispensable in some homeostatic contexts, establishing context-dependence of the TNKS–RNF146 axis.

    Evidence Morpholino knockdown with marker analysis in Xenopus; null-mutant genetics and epistasis in Drosophila

    PMID:28807725 PMID:30593492

    Open questions at the time
    • Molecular basis for context-dependent dispensability unknown
  7. 2020 Medium

    Distinguished tankyrase-dependent from tankyrase-independent RNF146 substrates proteome-wide, broadening its substrate landscape beyond the canonical PARdU model.

    Evidence Label-free proteomics with RNF146 KO and TNKS1/2-double KO cells, validating OTUD5, PARP10, and SARDH

    PMID:32958691

    Open questions at the time
    • Mechanism of PAR-independent substrate recognition unresolved
    • Many of the 160 candidates unvalidated
  8. 2020 Medium

    Revealed a ligase-independent protective function: RNF146 sequesters PAR polymer to block PARP1-driven parthanatos, downstream of Akt1/CREB transcriptional control.

    Evidence Constitutively active Akt1, luciferase reporters, PAR-binding assays, RNF146 KO mice, and SH-SY5Y toxicity assays

    PMID:33443209

    Open questions at the time
    • Relationship between sequestration and catalytic functions in the same cell not delineated
  9. 2022 High

    Placed RNF146 in innate antiviral control by showing it degrades TNKS-PARylated VISA/MAVS (at Glu137) to dampen interferon induction.

    Evidence Co-IP, Glu137 mutagenesis, ubiquitylation assays, RNF146/TNKS KO cells, in vivo viral infection

    PMID:35733260

    Open questions at the time
    • Temporal regulation during infection not mapped
  10. 2024 High

    Showed that adaptor-nucleated tankyrase/RNF146 liquid-like condensates execute PARdU of activated RIPK1 to restrain necroptosis, adding biomolecular condensation as an organizing principle of the axis.

    Evidence Phase-separation live imaging, K376 mutagenesis, ubiquitylation assays, Co-IP, and KO in MEFs

    PMID:38272024

    Open questions at the time
    • Whether condensate formation is required for other substrates is untested
  11. 2024 Medium

    Connected organelle homeostasis to the axis by showing peroxisome loss enhances TNKS/RNF146-dependent Axin1 degradation and Wnt output, with TNKS binding PEX14.

    Evidence Genome-wide CRISPRi screen with KO/knockdown, peroxisome import and substrate stability assays, and transcription reporters

    PMID:38967608

    Open questions at the time
    • Direct mechanism linking peroxisome status to TNKS activity unclear
  12. 2023 Medium

    Identified SUMOylation as a regulatory layer controlling RNF146 nucleocytoplasmic distribution and its efficiency in degrading Axin.

    Evidence Lysine mutagenesis, Co-IP, fractionation/immunofluorescence, ubiquitylation assays, and cancer models

    PMID:37029301

    Open questions at the time
    • Single-lab study; physiological triggers of RNF146 SUMOylation not defined
  13. 2025 Medium

    Cardiac studies expanded the substrate set (LKB1, PTEN, DAPK1) linking RNF146 degradation to AMPK suppression, AKT/mTOR activation, and ferroptosis/hypertrophy outcomes.

    Evidence Co-IP, cycloheximide chase, ubiquitylation assays, KO/overexpression and in vivo cardiac injury models

    PMID:34856161 PMID:35721496 PMID:39953324

    Open questions at the time
    • Several lack confirmed direct interaction or PAR-dependence
    • Low-confidence single-lab reports for DAPK1
  14. 2025 Low

    Characterized antagonism of RNF146 by a MAR-ubiquitin hybrid mark on tankyrase, showing how PAR chain extension — and thus PARdU — can be blocked to stabilize tankyrase.

    Evidence Biochemical ubiquitylation assays, mass spectrometry, and cell-based stability assays (preprint)

    PMID:bio_10.1101_2025.04.09.648013

    Open questions at the time
    • Preprint not independently replicated
    • Physiological relevance of the antagonism untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RNF146 selects among its many substrates in specific tissues, balances catalytic versus PAR-sequestering functions, and is regulated spatially (condensates, SUMOylation, export) remains incompletely integrated.
  • No unified model of substrate prioritization across tissues
  • Switch between ligase and sequestration modes undefined
  • In vivo relevance of condensate-based PARdU beyond necroptosis unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0140096 catalytic activity, acting on a protein 4 GO:0016874 ligase activity 2 GO:0140299 molecular sensor activity 2 GO:0140313 molecular sequestering activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-168256 Immune System 1
Partners
AMOTL2AXIN1MAVSPARP1RIPK1TNKS1TNKS2XPO1
Complex memberships
RNF146–tankyrase(TNKS1/2)–Axin complexTAX1BP1-nucleated tankyrase/RNF146 condensate

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 RNF146 is a RING-domain E3 ubiquitin ligase that directly interacts with poly(ADP-ribose) through its WWE domain, promoting ubiquitylation and proteasomal degradation of PARsylated proteins including Axin, BLZF1, and CASC3. RNF146 acts downstream of tankyrase-dependent PARsylation to couple PARsylation to ubiquitylation, thereby positively regulating Wnt/β-catenin signaling. RNAi screening, co-immunoprecipitation, proteomics, ubiquitylation assays, cell-based Wnt reporter assays Nature cell biology High 21478859
2011 RNF146, tankyrase, and Axin form a protein complex; RNF146 mediates ubiquitylation of Axin, TNKS1, and TNKS2 targeting all three for proteasomal degradation. RNF146 is a cytoplasmic protein that also prevents tankyrase aggregation at a centrosomal location. Tankyrase auto-PARsylation and RNF146-mediated ubiquitylation are mechanistically coupled in the same complex. RNAi screening, co-immunoprecipitation, ubiquitylation assays, immunofluorescence/localization studies, proteasome inhibitor experiments PloS one High 21799911
2014 Iso-ADP-ribose (the smallest internal PAR structural unit) binds between the WWE and RING domains of RNF146, acting as an allosteric signal that converts the RING domain from a catalytically inactive to an active state capable of binding E2 ubiquitin-conjugating enzymes. Crystal structure and biochemical analysis show PAR/iso-ADPr binding induces a major conformational change in RNF146. Additionally, RNF146 directly binds tankyrase via its C-terminal region; disruption of this interaction inhibits Axin turnover in cells. X-ray crystallography, biochemical binding assays, mutagenesis, E2-binding assays, cell-based Axin stability assays Nature High 25327252
2018 RNF146 binds directly to tankyrase (TNKS1/2) via multiple noncanonical tankyrase-binding motifs (TBMs) in its C-terminal region. These extended TBMs (with one or two extra residues between conserved Arg and Gly) mediate weak individual but strong multivalent binding. A crystal structure of the first RNF146 noncanonical TBM with the second ankyrin repeat domain of TNKS was solved. X-ray crystallography, binding/affinity assays, mutagenesis of TBMs Protein science High 29604130
2016 RNF146 and tankyrase2 (TNKS2) maintain the junctional Crumbs complex by promoting degradation of angiomotin (AMOT) family proteins. AMOT proteins are PARylated by TNKS2, which drives their ubiquitylation by RNF146 and subsequent proteasomal degradation. Ablation of RNF146 or tankyrase caused PALS1 (a Crumbs complex component) to relocate from the apical membrane to internal puncta, a phenotype rescued by AMOTL2 knockdown. RNAi knockdown, co-immunoprecipitation, ubiquitylation assays, immunofluorescence, genetic epistasis (rescue experiments) Journal of cell science High 27521426
2017 RANKL represses RNF146 transcription via an NF-κB-related inhibitory element in the RNF146 promoter. RANKL-mediated suppression of RNF146 stabilizes its substrates 3BP2 and AXIN1, triggering SRC activation and attenuation of β-catenin expression, respectively, to coordinate the osteoclast developmental program. RNF146 depletion caused hypersensitivity to LPS-induced TNF-α production in vivo. Promoter analysis, RNAi, genetic knockout, in vivo LPS challenge, co-immunoprecipitation, substrate stability assays The Journal of clinical investigation High 28287403
2017 Loss of RNF146 in osteoblasts stabilizes its substrate AXIN1, impairing WNT3a-induced β-catenin activation and reducing Fgf18 expression. FGF18 was shown to induce TAZ expression required for osteoblast proliferation and differentiation. RNF146 knockout also enhanced adipogenesis in MEFs and caused glucose intolerance with severe osteopenia. Genetic knockout (Rnf146-/- mice), cell-based Wnt/β-catenin reporter assays, substrate stability assays, osteoblast differentiation assays The Journal of clinical investigation High 28581440
2022 TNKS1 and TNKS2 PARylate the mitochondrial adaptor VISA/MAVS at Glu137, priming it for K48-linked polyubiquitination by RNF146 and subsequent proteasomal degradation. This mechanism attenuates innate antiviral signaling. RNF146 deficiency increased RNA virus-triggered interferon induction and impaired viral replication. Biochemical purification (co-immunoprecipitation), site-directed mutagenesis (Glu137), ubiquitylation assays, RNF146/TNKS knockout cells, in vivo viral infection model Proceedings of the National Academy of Sciences of the United States of America High 35733260
2020 Proteome-wide analysis using RNF146 KO and TNKS1/2-double KO cells identified 160 potential RNF146 substrates including 122 potential TNKS-independent substrates. OTUD5 and PARP10 were validated as TNKS1/2-independent substrates of RNF146, and SARDH was validated as a novel substrate of both TNKS1/2 and RNF146. Proteome profiling (label-free quantification), transcriptome analysis, CRISPR knockout cell lines, Western blot validation Molecular & cellular proteomics Medium 32958691
2023 RNF146 is SUMOylated at K19, K61, K174, and K175 by UBC9/PIAS3/MMS21, with SENP1/2/6 acting as deSUMOylases. SUMOylation (specifically at K19/K175, mediated by UBC9/PIAS3 and removed by SENP1) promotes RNF146 nuclear localization, while deSUMOylation induces cytoplasmic localization. SUMOylation promotes RNF146 association with Axin to accelerate Axin ubiquitylation and degradation, enhancing β-catenin signaling. Lysine mutagenesis, co-immunoprecipitation, subcellular fractionation/immunofluorescence, ubiquitylation assays, in vitro and in vivo cancer models Oncogene Medium 37029301
2014 In cardiac myocytes, RNF146 acts as a direct interactor of PARP-1. Upon PARP-1 activation by oxidative stress, RNF146 translocates from cytoplasm to nucleus, triggering PARP-1 nuclear exit followed by rapid proteasomal degradation of both PARP-1 and RNF146. RNF146 overexpression protected against oxidant-induced cell death; RNF146 silencing augmented PARP-1-mediated injury. Co-immunoprecipitation, overexpression/knockdown, immunofluorescence/live imaging, cardiomyocyte injury models Molecular medicine (Cambridge, Mass.) Medium 24842055
2020 Akt1 suppresses parthanatos in dopaminergic neurons by stimulating CREB-dependent transcriptional activation of the RNF146 gene. RNF146 inhibits PARP1-induced cell death not through its E3 ligase activity but by binding to and sequestering PAR polymer, thereby preventing parthanatos. Overexpression of constitutively active Akt1, luciferase reporter assays, co-immunoprecipitation/PAR binding assays, RNF146 KO in vivo mouse models, SH-SY5Y cell toxicity assays Science signaling Medium 33443209
2024 Upon induction of necroptosis and recruitment by the adaptor TAX1BP1, PARP5A (tankyrase) and RNF146 form liquid-like condensates through multivalent interactions. These condensates perform PARylation and PARylation-dependent ubiquitination (PARdU) of activated RIPK1, predominantly at K376, promoting proteasomal degradation of kinase-activated RIPK1 to restrain necroptosis in mouse embryonic fibroblasts. Phase separation assays (live imaging), mutagenesis (K376), ubiquitylation assays, co-immunoprecipitation, genetic KO (MEFs), cell death assays Molecular cell High 38272024
2018 In Drosophila, Rnf146 functions in the same proteolysis pathway as Tnks for Axin proteolysis in vivo (genetic epistasis), buffering Axin levels to ensure Wingless pathway activation in multiple developmental contexts. However, unlike Tnks, Rnf146 is dispensable for Wingless target gene activation and intestinal stem cell proliferation in the adult midgut during homeostasis, indicating context-dependent requirement for RNF146 in TNKS-mediated Axin degradation. Drosophila null mutant genetics, biochemical Axin stability assays, epistasis analysis, Wingless reporter assays Genetics Medium 30593492
2017 In Xenopus embryos, zygotic Rnf146 depletion via morpholino causes anteriorized development with increased Otx2 expression (consistent with positive Wnt regulation). Depletion of maternal Rnf146 leads to ventralized development and reduced organizer gene expression, demonstrating Rnf146 is required for Wnt-dependent embryonic pattern formation through negative regulation of Axin1. Morpholino knockdown, antisense oligonucleotide, in situ hybridization, marker gene expression analysis in Xenopus embryos Mechanisms of development Medium 28807725
2021 RNF146 promotes ubiquitylation and proteasomal degradation of LKB1 (Liver kinase B1) in cardiomyocytes, thereby suppressing the LKB1-AMPK signaling pathway to promote cardiac hypertrophy. RNF146 KO or knockdown increased AMPK pathway activation in a LKB1-dependent manner. Genetic KO mice (TAC model), RNAi knockdown, ubiquitylation assays, co-immunoprecipitation, Western blot, in vitro Ang II cardiomyocyte model Experimental cell research Medium 34856161
2022 RNF146 promotes ubiquitin-proteasome-mediated degradation of PTEN, thereby activating the AKT/mTOR pathway in hepatocellular carcinoma cells. RNF146 knockdown decreased PTEN ubiquitylation; MG132 (proteasome inhibitor) reversed RNF146-overexpression-induced PTEN reduction. RNF146 is transcriptionally regulated by HIF-1α/HIF-2α. RNAi knockdown, overexpression, proteasome inhibitor (MG132) rescue, ubiquitylation assays, Western blot, in vivo mouse xenograft Frontiers in cell and developmental biology Medium 35721496
2024 Inhibition of RNF146 reduces import of proteins into peroxisomes in a manner dependent on stabilization and activity of TNKS/TNKS2, which bind the peroxisomal membrane protein PEX14. Loss of peroxisomes increased TNKS/2- and RNF146-dependent degradation of AXIN1 sufficient to alter β-catenin transcription, linking peroxisome function to Wnt signaling through the RNF146-TNKS axis. Genome-wide CRISPRi screen, genetic KO/knockdown, peroxisome import assays, substrate stability assays, transcription reporter assays The Journal of cell biology Medium 38967608
2018 RNF146 is exported from the nucleus to the cytoplasm via an XPO1 (CRM1)-dependent nuclear export signal. Under angiotensin II (Ang II) stress, RNF146 accumulates in the nucleus; overexpression of XPO1 facilitates nuclear export of RNF146 and protects endothelial cells from Ang II-induced death. Interaction between RNF146 and XPO1 was confirmed by co-immunoprecipitation. Co-immunoprecipitation, XPO1 inhibitor (KPT-185), overexpression, immunofluorescence/subcellular fractionation, cell viability assays Biochemical and biophysical research communications Low 30029878
2025 RNF146 promotes ubiquitylation and proteasomal degradation of DAPK1 (death-associated protein kinase 1) in cardiomyocytes, thereby inhibiting ferroptosis and alleviating myocardial ischemia/reperfusion injury. Overexpressing DAPK1 reversed the cardioprotective effects of RNF146 overexpression. Co-immunoprecipitation, cycloheximide chase, ubiquitylation assays, overexpression/rescue experiments, in vivo MI/RI mouse model Cardiovascular toxicology Low 39953324
2025 DTX2 and DTX3 (Deltex E3 ligases) monoubiquitylate tankyrase on mono-ADP-ribose (MAR) residues rather than on lysine, creating a hybrid MAR-ubiquitin mark. RNF114 and RNF166 recognize this hybrid mark and further diubiquitylate it near the ADP-ribose addition site. This ubiquitylation of MAR prevents PAR chain extension on tankyrase, thereby antagonizing RNF146-mediated PARdU and stabilizing tankyrase. Thus, RNF146-dependent tankyrase degradation is counteracted by this MAR-ubiquitin hybrid mechanism. Biochemical ubiquitylation assays, mass spectrometry (identification of ubiquitin-MAR hybrid), cell-based tankyrase stability assays, domain binding studies bioRxivpreprint Low bio_10.1101_2025.04.09.648013
2025 The WWE domain of RNF146, when expressed as an EGFP fusion, functions as a genetically encoded probe for detecting PAR chains (specifically via iso-ADP-ribose recognition) at DNA damage sites in live cells, demonstrating unique PAR dynamics compared to other PAR-binding domains. Live-cell imaging (EGFP-WWE domain fusion), structural prediction, DNA damage induction, comparison across WWE domain variants DNA repair Low 40403420

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nature cell biology 373 21478859
2014 Allosteric activation of the RNF146 ubiquitin ligase by a poly(ADP-ribosyl)ation signal. Nature 197 25327252
2011 Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling. PloS one 183 21799911
2020 Activation of the Akt1-CREB pathway promotes RNF146 expression to inhibit PARP1-mediated neuronal death. Science signaling 38 33443209
2017 Ubiquitin ligase RNF146 coordinates bone dynamics and energy metabolism. The Journal of clinical investigation 36 28581440
2022 Tankyrases inhibit innate antiviral response by PARylating VISA/MAVS and priming it for RNF146-mediated ubiquitination and degradation. Proceedings of the National Academy of Sciences of the United States of America 35 35733260
2014 Overexpression of RNF146 in non-small cell lung cancer enhances proliferation and invasion of tumors through the Wnt/β-catenin signaling pathway. PloS one 34 24454854
2017 RANKL coordinates multiple osteoclastogenic pathways by regulating expression of ubiquitin ligase RNF146. The Journal of clinical investigation 32 28287403
2024 Bone-Targeting Peptide and RNF146 Modified Apoptotic Extracellular Vesicles Alleviate Osteoporosis. International journal of nanomedicine 29 38250192
2023 SUMOylation of RNF146 results in Axin degradation and activation of Wnt/β-catenin signaling to promote the progression of hepatocellular carcinoma. Oncogene 29 37029301
2014 Modulation of poly(ADP-ribose) polymerase-1 (PARP-1)-mediated oxidative cell injury by ring finger protein 146 (RNF146) in cardiac myocytes. Molecular medicine (Cambridge, Mass.) 29 24842055
2018 Structural basis for tankyrase-RNF146 interaction reveals noncanonical tankyrase-binding motifs. Protein science : a publication of the Protein Society 28 29604130
2018 The E3 ubiquitin ligase RNF146 promotes colorectal cancer by activating the Wnt/β-catenin pathway via ubiquitination of Axin1. Biochemical and biophysical research communications 28 29932918
2016 The RNF146 and tankyrase pathway maintains the junctional Crumbs complex through regulation of angiomotin. Journal of cell science 27 27521426
2023 Dysregulation of the Wnt/β-catenin signaling pathway via Rnf146 upregulation in a VPA-induced mouse model of autism spectrum disorder. Experimental & molecular medicine 25 37524878
2024 PARP5A and RNF146 phase separation restrains RIPK1-dependent necroptosis. Molecular cell 24 38272024
2005 The novel cytosolic RING finger protein dactylidin is up-regulated in brains of patients with Alzheimer's disease. The European journal of neuroscience 20 15813938
2017 RNF146 Inhibits Excessive Autophagy by Modulating the Wnt-β-Catenin Pathway in Glutamate Excitotoxicity Injury. Frontiers in cellular neuroscience 19 28321181
2020 NPD1 inhibits excessive autophagy by targeting RNF146 and wnt/β-catenin pathway in cerebral ischemia-reperfusion injury. Journal of receptor and signal transduction research 18 32326811
2020 Proteome-wide Analysis Reveals Substrates of E3 Ligase RNF146 Targeted for Degradation. Molecular & cellular proteomics : MCP 18 32958691
2024 Pimpinellin ameliorates macrophage inflammation by promoting RNF146-mediated PARP1 ubiquitination. Phytotherapy research : PTR 16 38323338
2022 HIF-1/2α-Activated RNF146 Enhances the Proliferation and Glycolysis of Hepatocellular Carcinoma Cells via the PTEN/AKT/mTOR Pathway. Frontiers in cell and developmental biology 16 35721496
2017 Estrogen receptor activation contributes to RNF146 expression and neuroprotection in Parkinson's disease models. Oncotarget 16 29290984
2019 Rhododendrin-Induced RNF146 Expression via Estrogen Receptor β Activation is Cytoprotective Against 6-OHDA-Induced Oxidative Stress. International journal of molecular sciences 13 30974833
2018 XPO1-mediated nuclear export of RNF146 protects from angiotensin II-induced endothelial cellular injury. Biochemical and biophysical research communications 11 30029878
2009 The RNF146 and ECHDC1 genes as candidates for inherited breast and ovarian cancer in Jewish Ashkenazi women. Familial cancer 11 19517271
2025 The Role of Dectin-1-Akt-RNF146 Pathway in β-Glucan Induced Immune Trained State of Monocyte in Sepsis. Journal of inflammation research 8 39881796
2021 The RING-domain E3 ubiquitin ligase RNF146 promotes cardiac hypertrophy by suppressing the LKB1/AMPK signaling pathway. Experimental cell research 8 34856161
2018 A Context-Dependent Role for the RNF146 Ubiquitin Ligase in Wingless/Wnt Signaling in Drosophila. Genetics 6 30593492
2017 The RNF146 E3 ubiquitin ligase is required for the control of Wnt signaling and body pattern formation in Xenopus. Mechanisms of development 6 28807725
2025 Overexpression of the WWE domain of RNF146 modulates poly-(ADP)-ribose dynamics at sites of DNA damage. DNA repair 5 40403420
2024 A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and TNKS/2. The Journal of cell biology 5 38967608
2025 RNF146 Alleviates Myocardial Ischemia/Reperfusion Injury by Regulating the Ubiquitination-Mediated Degradation of DAPK1 to Inhibit Ferroptosis. Cardiovascular toxicology 2 39953324
2024 Iso-ADP-Ribose Fluorescence Polarization Probe for the Screening of RNF146 WWE Domain Inhibitors. ACS chemical biology 2 38237916
2023 Overexpression of the WWE domain of RNF146 modulates poly-(ADP)-ribose dynamics at sites of DNA damage. bioRxiv : the preprint server for biology 1 38234836
2026 RNF146 enhances olaparib sensitivity in triple-negative breast cancer via XRCC5 downregulation. Biochemical and biophysical research communications 0 41932112
2024 A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and tankyrase. bioRxiv : the preprint server for biology 0 38352406
2023 Anesthesia and surgery induce changes in endogenous brain protective protein (RNF146) and delirium-like behavior in aged rats. Acta biochimica Polonica 0 37883680

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