Affinage

RNF126

E3 ubiquitin-protein ligase RNF126 · UniProt Q9BV68

Length
311 aa
Mass
33.9 kDa
Annotated
2026-04-28
37 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RNF126 is a RING-type E3 ubiquitin ligase that functions as a central effector of cytosolic protein quality control and participates in DNA damage signaling, membrane protein trafficking, and metabolic regulation. RNF126 is recruited to the BAG6 chaperone complex via its N-terminal Ubl domain and ubiquitinates mislocalized hydrophobic proteins, p97/VCP-extracted membrane protein substrates, and unimported mitochondrial precursors (via UBQLN1), targeting them for proteasomal degradation (PMID:24981174, PMID:32645369, PMID:40086734). In the DNA damage response, RNF126 ubiquitinates Ku80 to promote NHEJ completion (PMID:27895153), ubiquitinates MRE11 to activate ATR-CHK1 signaling and homologous recombination (PMID:36563124), and negatively regulates RNF168-mediated H2A ubiquitination to modulate 53BP1 recruitment (PMID:30529286, PMID:29167269); it also promotes BRCA1 expression in a ligase-independent manner by co-activating E2F1 (PMID:26234677). RNF126 ubiquitinates diverse additional substrates—including p21, p53, frataxin, PDKs, PTEN, and FSP1—linking it to cell cycle progression, ferroptosis, and metabolic reprogramming (PMID:23026136, PMID:28228265, PMID:27462466, PMID:33664240, PMID:38514855), and its deletion in mice causes meiotic arrest and male infertility with multiple morphological abnormalities of the sperm flagella (PMID:39142440, PMID:40410177).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2012 Medium

    Establishing RNF126 as an E3 ligase with an oncogenic substrate: before this work, RNF126's enzymatic targets were unknown; the study showed it directly ubiquitinates p21 for proteasomal degradation, driving G1-S cell cycle progression in cancer cells.

    Evidence Co-IP, ligase-dead mutant comparison, siRNA knockdown with p21 rescue in cancer cell lines

    PMID:23026136

    Open questions at the time
    • No in vitro reconstitution with purified components
    • Substrate selectivity over other CKIs not addressed
    • Single lab finding
  2. 2013 High

    Defining ubiquitin chain-type specificity and a role in receptor trafficking: RNF126 was shown to generate K48- or K63-linked chains depending on the E2 partner, and to regulate EGFR endosomal sorting and CI-MPR retrograde transport in a RING-dependent manner, broadening its functional scope beyond cell cycle control.

    Evidence In vitro chain-type reconstitution with UbcH5b and Ubc13/Uev1a; siRNA depletion with EGFR and CI-MPR trafficking assays

    PMID:23418353 PMID:24275455

    Open questions at the time
    • Direct EGFR ubiquitination site(s) not mapped
    • CI-MPR mechanism lacks in vitro reconstitution
    • Relationship between EGFR and CI-MPR sorting functions unclear
  3. 2014 High

    Revealing the core quality-control function: RNF126 was identified as the primary BAG6-dependent E3 ligase for mislocalized proteins, recruited via BAG6's Ubl domain and ubiquitinating juxtahydrophobic lysines on clients—establishing RNF126 as a central cytosolic triage enzyme.

    Evidence Full in vitro reconstitution with purified components, cell fractionation, RNF126 depletion

    PMID:24981174

    Open questions at the time
    • Structural basis of Ubl-mediated recruitment not resolved
    • In vivo substrate scope not defined genome-wide
  4. 2015 Medium

    Uncovering a ligase-independent transcriptional function: RNF126 was found to bind E2F1 and co-activate BRCA1 transcription independently of its RING catalytic activity, promoting homologous recombination—demonstrating a non-enzymatic role distinct from its ubiquitin ligase function.

    Evidence Co-IP of RNF126-E2F1, ChIP at BRCA1 promoter, RING-independent rescue of HR, PARP inhibitor sensitivity

    PMID:26234677

    Open questions at the time
    • Single lab; independent validation needed
    • Structural determinant of E2F1 binding beyond 11-aa deletion not mapped
    • Unclear whether E2F1-dependent function is tissue-specific
  5. 2016 Medium

    Linking RNF126 to metabolic reprogramming: RNF126 was shown to ubiquitinate pyruvate dehydrogenase kinases (PDKs) for degradation, increasing PDH activity and acetyl-CoA flux, thereby supporting anoikis resistance—connecting its E3 ligase activity to cancer metabolism.

    Evidence PDK ubiquitination assay, metabolic flux analysis, soft-agar and in vivo tumorigenicity assays

    PMID:27462466

    Open questions at the time
    • Specific PDK isoform selectivity not fully defined
    • No in vitro reconstitution with purified components
  6. 2017 High

    Establishing roles in NHEJ and frataxin homeostasis: RNF126 was shown to ubiquitinate Ku80 (with UBE2D3) to promote Ku release from DSBs and NHEJ completion, and independently to ubiquitinate frataxin for proteasomal degradation—identifying it as a therapeutic target for Friedreich ataxia.

    Evidence In vitro ubiquitylation, Ku80 K→R site mutagenesis, chromatin fractionation, frataxin stability in FRDA patient cells

    PMID:27895153 PMID:28228265

    Open questions at the time
    • Whether Ku80 ubiquitination is BAG6-dependent is unknown
    • Frataxin ubiquitination sites not mapped
    • RNF126 inhibitor pharmacology not explored
  7. 2017 Medium

    Placing RNF126 as a negative regulator in the DDR ubiquitin cascade: overexpression studies showed RNF126 suppresses RNF168-mediated H2A K13/15 monoubiquitination and 53BP1 foci while leaving γH2AX, MDC1, and RNF8 foci intact, positioning RNF126 between RNF8 and RNF168.

    Evidence IR-induced foci hierarchy analysis, H2A ubiquitination assay, NHEJ reporter assay

    PMID:29167269

    Open questions at the time
    • Endogenous regulation versus overexpression artifacts not fully resolved
    • Mechanism of RNF168 inhibition (direct ubiquitination vs. competition) not yet distinguished
  8. 2018 Medium

    Confirming direct RNF168 ubiquitination: RNF126 was shown to be recruited to damage sites in an RNF8-dependent manner and to directly ubiquitinate RNF168, resolving the mechanism of its negative regulation of the DDR.

    Evidence UV laser micro-irradiation recruitment, Co-IP of RNF126-RNF168, catalytic-dead mutant discrimination

    PMID:30529286

    Open questions at the time
    • Ubiquitination sites on RNF168 not mapped
    • Chain type used on RNF168 not determined
    • Single lab
  9. 2020 High

    Extending the quality-control paradigm to ERAD: RNF126 was shown to reubiquitinate p97/VCP-extracted membrane proteins via BAG6, reconstituting the ternary complex and demonstrating that cytosolic reubiquitination is essential for proteasomal targeting of retrotranslocated substrates.

    Evidence In vitro reconstitution with purified factors, pulse-chase turnover, cellular depletion

    PMID:32645369

    Open questions at the time
    • Selectivity for specific ERAD substrates not comprehensively defined
    • Interplay with other cytosolic reubiquitination E3s (e.g., CHIP) not addressed
  10. 2021 Medium

    Expanding substrate range to innate immunity and cell cycle checkpoint maintenance: RNF126 was shown to K63-ubiquitinate TRAF3 for antiviral signaling and to stabilize 14-3-3σ for G2 arrest maintenance, while its own stability was found to be regulated by PARP1-mediated PARylation and CHFR-dependent ubiquitination.

    Evidence Co-IP with chain-type specificity assays, PARylation/CHFR recruitment assay, cycloheximide stability, cell cycle analysis

    PMID:34388456 PMID:34563636 PMID:34643674

    Open questions at the time
    • TRAF3 ubiquitination sites not mapped
    • 14-3-3σ stabilization mechanism (direct deubiquitination vs. shielding) not resolved
    • PARP1-CHFR-RNF126 axis not reconstituted in vitro
  11. 2022 Medium

    Activating ATR signaling through MRE11 ubiquitination: RNF126 was found to ubiquitinate MRE11 at K339/K480, enhancing its exonuclease activity and RPA binding, thereby activating ATR-CHK1 and promoting HR—adding a positive arm to RNF126's DDR involvement.

    Evidence Co-IP with MRN complex, site-specific ubiquitination mapping, exonuclease activity assay, ATR phosphorylation, KO mouse

    PMID:36563124

    Open questions at the time
    • How RNF126 simultaneously promotes (MRE11 activation) and inhibits (RNF168 degradation) DDR signaling is not integrated
    • Chain type on MRE11 not defined
    • Single lab
  12. 2024 Medium

    Connecting RNF126 to ferroptosis: RNF126 was shown to ubiquitinate FSP1 at defined sites, displacing it from the plasma membrane, increasing the CoQ/CoQH₂ ratio, and promoting ferroptosis in medulloblastoma—identifying a new mechanism for ferroptosis regulation.

    Evidence Co-IP, site-specific ubiquitination, subcellular fractionation, CoQ ratio measurement, in vivo ferroptosis assay

    PMID:38514855

    Open questions at the time
    • Whether BAG6 is involved in FSP1 targeting is unknown
    • Generalizability beyond Group 3 medulloblastoma not tested
  13. 2024 Medium

    Demonstrating physiological requirement for male fertility: RNF126 knockout mice exhibited meiosis I arrest, flagellar defects (MMAF), and complete male infertility; RING-domain missense variants abolished ligase activity, and RNF126-BAG6 interaction was confirmed in sperm cells.

    Evidence Rnf126 KO mouse, flagellar ultrastructure, RING-domain mutant enzymatic assay, Co-IP in germ cells, association with human infertility variants

    PMID:39142440 PMID:40410177

    Open questions at the time
    • Specific spermatogenesis substrates not identified
    • Whether BAG6 quality control of tail-anchored proteins underlies flagellar defect is speculative
  14. 2025 High

    Expanding the quality-control paradigm to mitochondrial import stress: RNF126 was shown to interact with substrate-engaged UBQLN1 and ubiquitinate unimported mitochondrial precursors (ATP5G1) for proteasomal clearance, defining a UBQLN1-dependent branch of RNF126 quality control distinct from BAG6.

    Evidence In vitro reconstitution of RNF126-UBQLN1-ATP5G1 ternary complex, Co-IP, proteasomal degradation assay

    PMID:40086734

    Open questions at the time
    • Scope of UBQLN1-dependent substrates unknown
    • Whether BAG6 and UBQLN1 pathways are competitive or parallel not addressed
  15. 2025 Medium

    Non-canonical ubiquitination and late-mitotic DDR functions: RNF126 was found to ubiquitinate midnolin at non-canonical Cys/Ser/Thr residues, and to accumulate with BRAP in an ATM-dependent manner during late mitosis to promote 53BP1/RPA2 focus formation and DNA lesion resolution.

    Evidence MS-based non-canonical ubiquitination site mapping, proteomic analysis of late-mitotic irradiated cells, 53BP1/RPA2 foci and clonogenic survival with RNF126 depletion

    PMID:41496599 PMID:41996237

    Open questions at the time
    • Physiological significance of non-lysine ubiquitination on midnolin stability versus function not clarified
    • BRAP-RNF126 physical interaction and mechanism not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how RNF126 balances its positive (MRE11, Ku80, BRCA1) and negative (RNF168) roles in the DDR in a context-dependent manner; the structural basis of BAG6 Ubl-mediated recruitment; the full in vivo substrate repertoire; and whether its quality-control and DDR functions are coordinately regulated.
  • No structural model of RNF126 in complex with BAG6 or substrates
  • Genome-wide substrate identification not performed
  • Context-dependent switching between DDR-promoting and DDR-inhibiting functions not mechanistically explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 12 GO:0016874 ligase activity 5 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005694 chromosome 2
Pathway
R-HSA-392499 Metabolism of proteins 7 R-HSA-73894 DNA Repair 5 R-HSA-1474165 Reproduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-168256 Immune System 1 R-HSA-5357801 Programmed Cell Death 1
Partners
BAG6E2F1MRE11PARP1RNF168SFNUBQLN1XRCC5
Complex memberships
BAG6 chaperone complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 RNF126 is the primary Bag6-dependent E3 ubiquitin ligase for cytosolic quality control of mislocalized proteins (MLPs). RNF126 is recruited to the N-terminal Ubl domain of Bag6 and preferentially ubiquitinates juxtahydrophobic lysine residues on Bag6-associated clients. Bag6-dependent ubiquitination was fully reconstituted with purified components. In vitro reconstitution with purified components, cell fractionation, Bag6-dependent ubiquitination assay, RNF126 depletion in cells Molecular cell High 24981174
2020 RNF126 catalyzes reubiquitination of p97/VCP-extracted membrane proteins in the cytosol. RNF126 interacts with BAG6, which captures p97-liberated substrates, and a ternary complex (RNF126-BAG6-substrate) was reconstituted with purified factors to demonstrate reubiquitination required for proteasomal targeting. In vitro reconstitution with purified factors, cellular depletion of RNF126, stabilization of extracted intermediates, pulse-chase turnover assays Molecular cell High 32645369
2025 RNF126 interacts with substrate-engaged UBQLN1 via UBQLN1's ubiquitin-associated (UBA) domain and catalyzes ubiquitination of unimported mitochondrial membrane protein precursors (e.g., ATP5G1), promoting their proteasomal degradation during mitochondrial stress. Ternary complex formation (RNF126-UBQLN1-ATP5G1) was reconstituted in vitro. In vitro reconstitution of ternary complex, co-IP, ubiquitination assay, proteasomal degradation assay with RNF126 depletion The Journal of biological chemistry High 40086734
2012 RNF126 acts as an E3 ubiquitin ligase that directly interacts with p21 and promotes its ubiquitination and proteasomal degradation in an E3 ligase activity-dependent manner, driving cancer cell proliferation and G1-S progression. Co-immunoprecipitation, ubiquitination assay with overexpression of WT vs. ligase-dead RNF126, siRNA knockdown with protein stability assay, rescue by p21 depletion Cancer research Medium 23026136
2017 RNF126 ubiquitylates Ku80 (with UBE2D3 as E2) at DSBs, promoting Ku70/80 dissociation from damaged DNA and completion of NHEJ repair. Lysine-to-arginine mutation of Ku80 ubiquitylation sites delayed Ku70/80 release from chromatin. Identification by mass spectrometry interactome, Co-IP, in vitro ubiquitylation assay, Ku80 ubiquitylation-site mutagenesis (K→R), chromatin fractionation, RNF126 knockdown with DSB repair assay Molecular and cellular biology High 27895153
2013 RNF126 specifies K48-linked ubiquitin chains with UbcH5b and K63-linked chains with Ubc13/Uev1a in vitro. RNF126 associates with EGFR via a ubiquitin-binding zinc finger domain and promotes EGFR ubiquitylation downstream of c-Cbl, regulating EGFR endosomal sorting and ESCRT-II stability. In vitro ubiquitin chain-type assay, Co-IP, siRNA depletion with EGFR trafficking/degradation assay, multivesicular body quantification Journal of cell science High 23418353
2013 RNF126 regulates retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR); its RING finger domain (ligase activity) is required, as RING-domain mutant fails to rescue CI-MPR missorting upon RNF126 depletion. siRNA stable knockdown, RING-domain mutant rescue experiment, CI-MPR localization by immunofluorescence, lysosomal degradation assay, cathepsin D missorting Experimental cell research Medium 24275455
2016 RNF126 acts as an E3 ubiquitin ligase for pyruvate dehydrogenase kinases (PDKs), targeting them for proteasomal degradation. This increases PDH activity and pyruvate-to-acetyl-CoA flux, supporting TCA cycle activity and anoikis resistance in cancer cells. RNF126 expression is controlled by ERK signaling. Ubiquitination assay for PDKs, proteasomal degradation assay, metabolic flux analysis, soft-agar colony assay, RNF126 depletion in vivo tumorigenicity Cell discovery Medium 27462466
2017 RNF126 is the E3 ligase that directly ubiquitinates frataxin, targeting it for proteasomal degradation. RNF126 interacts with frataxin and promotes its ubiquitination in a catalytic activity-dependent manner both in vivo and in vitro; RNF126 depletion raises frataxin levels in Friedreich ataxia patient-derived cells. Co-immunoprecipitation, in vitro and in vivo ubiquitination assay, catalytic mutant comparison, protein stability assay in FRDA patient cells Cell reports High 28228265
2015 RNF126 promotes homologous recombination by facilitating BRCA1 expression through direct binding to transcription factor E2F1, enhancing E2F1-mediated transactivation of the BRCA1 promoter; this function is independent of RNF126 E3 ligase activity. An 11-amino-acid deletion mutant acts dominantly negatively by preventing E2F1 binding. Co-IP of RNF126-E2F1, BRCA1 promoter luciferase assay, ChIP for E2F1 at BRCA1 promoter, deletion mutant analysis, HR repair assay, ionizing radiation and PARP inhibitor sensitivity Oncogene Medium 26234677
2018 RNF126 is recruited to DNA damage sites in an RNF8-dependent manner, directly interacts with RNF168, and ubiquitinates RNF168. RNF126 overexpression (but not catalytic-dead mutant) diminishes RNF168-mediated H2AX ubiquitination and downstream 53BP1/RAP80/BRCA1 focus formation, placing RNF126 between RNF8 and RNF168 in the DDR cascade. UV laser micro-irradiation recruitment, Co-IP of RNF126-RNF168, ubiquitination assay with WT vs. CC229/232AA catalytic mutant, HR repair assay Genomics, proteomics & bioinformatics Medium 30529286
2017 RNF126 overexpression abolishes 53BP1 iRIF formation and RNF168-mediated H2A monoubiquitination at K13/15, while γH2AX, MDC1, and RNF8 foci are maintained, placing RNF126 as a negative regulator between RNF8 and RNF168 in the DDR and inhibiting NHEJ. Ionizing radiation-induced foci screen, overexpression and focus formation analysis, H2A ubiquitination assay, NHEJ assay The Journal of biological chemistry Medium 29167269
2022 RNF126 physically associates with the MRE11-RAD50-NBS1 complex and ubiquitinates MRE11 at K339 and K480, increasing MRE11 DNA exonuclease activity, RPA binding, and ATR phosphorylation, thereby activating the ATR-CHK1 DDR pathway and promoting homologous recombination repair after irradiation. Co-IP of RNF126 with MRN complex, site-specific ubiquitination (K339/K480) mapping, MRE11 exonuclease activity assay, RPA binding assay, ATR phosphorylation measurement, RNF126 depletion in cells and mice Advanced science Medium 36563124
2021 PARP1 interacts with RNF126 and poly(ADP-ribosyl)ates it, recruiting the PAR-binding E3 ligase CHFR to promote ubiquitination and degradation of RNF126 itself, constituting a post-translational regulatory mechanism that modulates RNF126 protein stability. Co-IP of PARP1-RNF126, PARylation assay, CHFR recruitment assay, ubiquitination and degradation of RNF126, RNF126 depletion effect on ATR-CHK1 signaling Biochemical and biophysical research communications Medium 34388456
2021 RNF126 binds 14-3-3σ and prevents both proteins from ubiquitination-mediated degradation, thereby promoting cytoplasmic sequestration of cyclin B1 and CDK1 and maintaining IR-induced G2 arrest. GST-pulldown, Co-IP, cycloheximide stability assay, ubiquitination assay, immunofluorescence for CDK1/cyclin B1 localization, flow cytometry for cell cycle International journal of radiation oncology, biology, physics Medium 34563636
2021 RNF126 interacts with TRAF3 and promotes its K63-linked polyubiquitination in the antiviral response. RNF126 also interacts with deubiquitinase OTUB1 and promotes ubiquitination of OTUB1 at C91, reducing OTUB1 catalytic activity toward TRAF3. Co-IP of RNF126 with TRAF3 and OTUB1, K63-specific ubiquitination assay, OTUB1 C91 ubiquitination and activity assay Bioscience, biotechnology, and biochemistry Medium 34643674
2021 RNF126 interacts with PTEN and promotes its poly-ubiquitination and degradation, binding to the C-terminal RING-domain-containing region of RNF126; this activates the EGFR/PI3K/AKT signaling pathway in bladder cancer. Co-immunoprecipitation, in vivo ubiquitination assay, domain-mapping, RNF126 knockdown/overexpression with AKT pathway readout Cell death & disease Medium 33664240
2017 ANG II activates ERK/GSK3 to phosphorylate HSF1 (S307 by ERK, S303 by GSK3), leading to downregulation of RNF126 expression; reduced RNF126 stabilizes its substrate IGF-IIR, promoting cardiomyocyte hypertrophy. Western blotting of phospho-HSF1, RNF126 expression after ANG II/ERK/GSK3 modulation, IGF-IIR stability assay, in vivo GSK3 inhibition in cardiac hypertrophy model Journal of cellular physiology Medium 28383811
2024 RNF126 interacts with FSP1 (AIFM2) and ubiquitinates it at 4KR-2 sites, altering FSP1 subcellular localization away from the plasma membrane, increasing the CoQ/CoQH2 ratio and promoting phospholipid peroxidation and ferroptosis in Group 3 medulloblastoma. Co-IP, ubiquitination assay at defined sites, subcellular fractionation/localization, CoQ/CoQH2 ratio measurement, ferroptosis assay in vivo and in vitro Oncogene Medium 38514855
2024 RNF126 is required for spermatogenesis and male fertility; its RING domain missense variants (E261A, D253N) directly compromise E3 ubiquitin ligase activity. RNF126 deletion in mice causes meiosis I arrest, impaired homologous recombination repair, and increased apoptosis in seminiferous tubules. Homozygous Rnf126 knockout mouse model, sperm count analysis, histology, RING-domain mutant ubiquitin ligase assay, association with human infertility variants Journal of advanced research Medium 39142440
2020 RNF126 promotes ubiquitination and degradation of p53 in wild-type p53 colorectal cancer cells; RNF126 co-immunoprecipitates with both p53 and p21 forming a triple complex, and RNF126 silencing/overexpression reciprocally regulates p53 and p21 protein (but not mRNA) levels. Co-IP (triple complex), ubiquitination assay, MG132 rescue, cycloheximide stability, siRNA knockdown and overexpression OncoTargets and therapy Medium 33149608
2022 RNF126 ubiquitinates LKB1, promoting its degradation and reducing its stability, thereby enhancing stem-cell-like activity, migration, and angiogenesis in hepatocellular carcinoma. Co-IP, ubiquitination assay, RNF126 knockdown/overexpression with LKB1 stability and HCC phenotype readouts, in vivo xenograft Human cell Low 36068398
2025 RNF126 negatively regulates mTORC1 signaling by promoting K63-linked ubiquitination of ILF3, and silencing RNF126 attenuates ILF3-GATOR2 interaction. Co-IP, K63-specific ubiquitination assay, RNF126 siRNA depletion with mTORC1 activity readout, ILF3-GATOR2 interaction assay Cellular signalling Low 40907628
2026 RNF126 ubiquitinates midnolin (MIDN) at non-canonical cysteine, serine, and threonine residues (C230, C236, S237, T239, S241), not lysines, targeting it for 26S proteasomal degradation. This RNF126-MIDN axis governs EGR1 abundance and PTEN/p53 levels, affecting testicular germ-cell tumor progression. Co-IP, mass spectrometry-based ubiquitination site mapping, ubiquitination assay, proteasomal degradation assay Acta biochimica et biophysica Sinica Medium 41496599
2026 RNF126 ubiquitinates METTL17 at K116, targeting it for proteasomal degradation. SIRT5 acts as a desuccinylase removing succinylation at METTL17 K274, facilitating RNF126-mediated ubiquitination and degradation in a coordinated SIRT5-METTL17-RNF126 regulatory axis in glioma. Mass spectrometry, Co-IP, ubiquitination assay (K116), SIRT5 desuccinylation assay (K274), RNF126 depletion with METTL17 stability readout, in vivo xenograft Cell & bioscience Medium 42021405
2026 RNF126 and BRAP accumulate in an ATM-dependent manner in late mitotic (anaphase/telophase) cells after DNA damage, and both are required for 53BP1 and RPA2 focus formation, DNA lesion resolution, and cell survival after late mitotic irradiation. Proteomic analysis of late mitotic irradiated cells, functional assays (53BP1/RPA2 foci, γH2AX resolution, clonogenic survival) with RNF126 depletion Cell reports Medium 41996237
2025 RNF126 interacts with BAG6 in sperm cells to regulate sperm synthesis and germ cell development; RNF126 deficiency in mice causes MMAF (multiple morphological abnormalities of the flagella), germ cell apoptosis, and infertility. Genetic lineage tracing, RNF126 KO mouse, Co-IP of RNF126-BAG6, ultrastructural flagellar analysis, sperm count Cell death discovery Medium 40410177

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Cytosolic quality control of mislocalized proteins requires RNF126 recruitment to Bag6. Molecular cell 150 24981174
2012 E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation. Cancer research 64 23026136
2022 RNF126-Mediated MRE11 Ubiquitination Activates the DNA Damage Response and Confers Resistance of Triple-Negative Breast Cancer to Radiotherapy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 57 36563124
2017 Ubiquitylation of Ku80 by RNF126 Promotes Completion of Nonhomologous End Joining-Mediated DNA Repair. Molecular and cellular biology 52 27895153
2013 The E3 ubiquitin ligases RNF126 and Rabring7 regulate endosomal sorting of the epidermal growth factor receptor. Journal of cell science 48 23418353
2021 E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability. Cell death & disease 47 33664240
2016 The ERK signaling target RNF126 regulates anoikis resistance in cancer cells by changing the mitochondrial metabolic flux. Cell discovery 47 27462466
2015 RNF126 promotes homologous recombination via regulation of E2F1-mediated BRCA1 expression. Oncogene 46 26234677
2020 RNF126-Mediated Reubiquitination Is Required for Proteasomal Degradation of p97-Extracted Membrane Proteins. Molecular cell 43 32645369
2017 E3 Ligase RNF126 Directly Ubiquitinates Frataxin, Promoting Its Degradation: Identification of a Potential Therapeutic Target for Friedreich Ataxia. Cell reports 38 28228265
2017 HSF1 phosphorylation by ERK/GSK3 suppresses RNF126 to sustain IGF-IIR expression for hypertension-induced cardiomyocyte hypertrophy. Journal of cellular physiology 32 28383811
2022 Tumor cell-derived exosome RNF126 affects the immune microenvironment and promotes nasopharyngeal carcinoma progression by regulating PTEN ubiquitination. Apoptosis : an international journal on programmed cell death 28 35717659
2024 RNF126-mediated ubiquitination of FSP1 affects its subcellular localization and ferroptosis. Oncogene 22 38514855
2016 E3 Ubiquitin ligase RNF126 regulates the progression of tongue cancer. Cancer medicine 21 27227488
2020 Roles of RNF126 and BCA2 E3 ubiquitin ligases in DNA damage repair signaling and targeted cancer therapy. Pharmacological research 20 32147403
2018 RNF126 Quenches RNF168 Function in the DNA Damage Response. Genomics, proteomics & bioinformatics 20 30529286
2020 Overexpression of RNF126 Promotes the Development of Colorectal Cancer via Enhancing p53 Ubiquitination and Degradation. OncoTargets and therapy 15 33149608
2013 The ubiquitin ligase RNF126 regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor. Experimental cell research 15 24275455
2017 Ring finger protein 126 (RNF126) suppresses ionizing radiation-induced p53-binding protein 1 (53BP1) focus formation. The Journal of biological chemistry 14 29167269
2024 ZNF263 cooperates with ZNF31 to promote the drug resistance and EMT of pancreatic cancer through transactivating RNF126. Journal of cellular physiology 9 38515383
2021 CHFR-mediated degradation of RNF126 confers sensitivity to PARP inhibitors in triple-negative breast cancer cells. Biochemical and biophysical research communications 8 34388456
2021 A Novel Role for RNF126 in the Promotion of G2 Arrest via Interaction With 14-3-3σ. International journal of radiation oncology, biology, physics 7 34563636
2022 RNF126 contributes to stem cell-like properties and metastasis in hepatocellular carcinoma through ubiquitination and degradation of LKB1. Human cell 5 36068398
2024 An essential role of the E3 ubiquitin ligase RNF126 in ensuring meiosis I completion during spermatogenesis. Journal of advanced research 4 39142440
2025 Absence of Rnf126 causes male infertility with multiple morphological abnormalities of the sperm flagella. Cell death discovery 3 40410177
2024 Design, synthesis and biological evaluation of new RNF126-based p300/CBP degraders. Bioorganic chemistry 3 38728911
2021 RNF126 is a positive regulator of TRAF3 ubiquitination. Bioscience, biotechnology, and biochemistry 3 34643674
2025 The E3 ubiquitin ligase RNF126 facilitates quality control of unimported mitochondrial membrane proteins. The Journal of biological chemistry 2 40086734
2025 Ring-Finger Protein 126 (RNF126) Promotes Anoikis Resistance and Peritoneal Colonization in Ovarian Cancer. International journal of molecular sciences 2 41465608
2023 RNF126, 168 and CUL1: The Potential Utilization of Multi-Functional E3 Ubiquitin Ligases in Genome Maintenance for Cancer Therapy. Biomedicines 2 37760968
2026 An Optimized RNF126-Targeting Covalent Handle for Molecular Glue Degraders. bioRxiv : the preprint server for biology 1 41867716
2025 RNF126 Promotes Ovarian Cancer Progression by Reprogramming Lipid Metabolism Through Degradation of ACAP2. Biochemical genetics 1 40251363
2025 Ring-finger protein RNF126 promotes prostate cancer progression via regulation of MBNL1. Scientific reports 1 40615482
2025 RNF126 suppresses amino acid-mediated mTORC1 signaling pathway by ubiquitinating ILF3 in HEK293T cells. Cellular signalling 1 40907628
2026 RNF126 writes a non-canonical ubiquitin code on midnolin to tune protein stability. Acta biochimica et biophysica Sinica 0 41496599
2026 RNF126 and BRAP safeguard genome integrity after DNA damage in late mitosis. Cell reports 0 41996237
2026 SIRT5-RNF126 coordinated regulation of METTL17 stability controls mitochondrial function and glioma progression. Cell & bioscience 0 42021405