Affinage

PELI1

E3 ubiquitin-protein ligase pellino homolog 1 · UniProt Q96FA3

Length
418 aa
Mass
46.3 kDa
Annotated
2026-06-10
61 papers in source corpus 29 papers cited in narrative 28 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

PELI1 is a RING-like domain E3 ubiquitin ligase that operates at the intersection of TLR/innate immunity, NF-κB signaling, cell death, and metabolic control, using its FHA domain to read phosphorylated substrates and its RING domain to catalyze ubiquitin transfer with linkage-specific outcomes (PMID:19734906, PMID:29883609, PMID:30269743). In TLR signaling it conjugates K63-linked chains onto RIP1 to drive TRIF-dependent IKK–NF-κB activation (PMID:19734906), while shaping inflammation through degradative ubiquitination of inhibitory factors—K48-linked degradation of c-Rel to restrain T cell activation and prevent autoimmunity (PMID:21874024), TRAF3 degradation to license MAPK-driven microglial activation (PMID:23603814), and K48-linked degradation of NIK to suppress noncanonical NF-κB in B cells (PMID:29555915). PELI1 is a bidirectional rheostat of programmed cell death: it promotes necroptosis by K63-linked ubiquitination of RIPK1 at K115 to nucleate the RIPK1–RIPK3 necrosome (PMID:29078411), yet limits it by selectively K48-ubiquitinating kinase-active RIP3 at K363 for proteasomal degradation (PMID:29883609, PMID:30269743). Beyond cell death, it controls metabolism and growth signaling through non-degradative ubiquitination of TSC1 that stabilizes the TSC1–TSC2 complex to inhibit mTORC1 and T cell glycolysis (PMID:33215753), and amplifies innate immune output by K63-linked ubiquitination of ASC at K55 to assemble the NLRP3 inflammasome (PMID:34706239). The FHA domain confers phospho-substrate selectivity, recognizing phosphorylated HPD and RPS3 to target them for degradation (PMID:31537781, PMID:38528516). Across diverse tissues PELI1 additionally directs degradative ubiquitination of transcription factors and regulators including HNF4α, C/EBPβ, Foxp1, Mdmx, and IRF5, linking it to cardiac, hepatic, and tumor-associated phenotypes (PMID:38346961, PMID:33017390, PMID:39618410, PMID:29523541, PMID:36822176).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 2009 High

    Established PELI1 as a substrate-specific E3 ligase in TLR signaling by showing it K63-ubiquitinates RIP1 to drive TRIF- but not MyD88-dependent NF-κB activation, defining its pathway selectivity.

    Evidence Co-IP, in vitro ubiquitination, and knockout mice across TLR contexts

    PMID:19734906

    Open questions at the time
    • Did not map the ubiquitination site on RIP1
    • FHA/RING domain contributions not dissected here
  2. 2011 High

    Showed PELI1 also acts as a brake on NF-κB by K48-degradative ubiquitination of c-Rel, explaining the spontaneous autoimmunity of Peli1-deficient mice and revealing dual activating/inhibitory roles.

    Evidence Knockout mice, ubiquitination assays, nuclear fractionation, T cell activation assays

    PMID:21874024

    Open questions at the time
    • c-Rel ubiquitination site not mapped
    • Mechanism distinguishing activating vs degradative targeting unresolved
  3. 2013 High

    Extended PELI1's reach to MAPK signaling by demonstrating TRAF3 degradation enables microglial TLR responses, with genetic epistasis confirming TRAF3 as the relevant target.

    Evidence Knockout mice, EAE model, TRAF3 protein analysis, Traf3 ablation rescue

    PMID:23603814

    Open questions at the time
    • Direct in vitro TRAF3 ubiquitination not shown
    • Ubiquitin linkage type on TRAF3 unspecified
  4. 2015 Medium

    Identified PELI1 as a negative regulator of type I interferon in the CNS, broadening its innate immune function to antiviral responses.

    Evidence Peli1-KO mice, intranasal VSV infection, IFN-β and viral titer assays

    PMID:26131354

    Open questions at the time
    • Molecular target downstream of E3 activity not identified
    • Mechanism of IFN-I suppression unresolved
  5. 2017 High

    Defined PELI1 as a necroptosis driver by mapping kinase-dependent K63 ubiquitination of RIPK1-K115 that promotes necrosome formation, establishing a positive role in regulated necrosis.

    Evidence Site-directed mutagenesis (K115), RIPK1-RIPK3 Co-IP, kinase inhibitor experiments, KO cells/mice

    PMID:29078411

    Open questions at the time
    • Relationship between c-FLIP mRNA maintenance and ligase activity unclear
    • How kinase activity gates ubiquitination not structurally resolved
  6. 2018 High

    Revealed PELI1 also restrains necroptosis by FHA-dependent recognition of phospho-T182 RIP3 and K48 ubiquitination at K363, showing opposing control of the RIPK1 vs RIP3 nodes.

    Evidence Reconstituted in vitro ubiquitination, T182/K363 mutants, proteasome inhibitors, FHA mapping; replicated by companion paper

    PMID:29883609 PMID:30269743

    Open questions at the time
    • Determinant choosing K63-RIPK1 vs K48-RIP3 outcomes not defined
    • In vivo balance of the two activities not resolved
  7. 2018 High

    Showed PELI1 suppresses noncanonical NF-κB via K48 ubiquitination of NIK in B cells, linking its loss to lupus-like autoantibody production.

    Evidence Co-IP, ubiquitination assays, B cell-specific conditional KO, lupus model

    PMID:29555915

    Open questions at the time
    • NIK ubiquitination site not mapped
    • Recruitment mechanism to NIK unresolved
  8. 2018 High

    Connected PELI1 to tumor suppression control by non-degradative ubiquitination of Mdmx that drives its cytoplasmic retention and sustains p53 activity.

    Evidence Co-IP, in vitro binding/ubiquitination, subcellular fractionation, Peli1-KO Myc tumor model

    PMID:29523541

    Open questions at the time
    • Ubiquitin linkage on Mdmx not characterized
    • Direct effect on p53 binding partners not dissected
  9. 2019 High

    Demonstrated FHA-domain phospho-recognition as a general PELI1 substrate-selection mechanism by showing it degrades STK33-phosphorylated HPD, with TTC36 antagonizing recruitment.

    Evidence Co-IP, in vitro kinase and ubiquitination assays, Ttc36-KO tyrosinemia model

    PMID:31537781

    Open questions at the time
    • HPD ubiquitination site not mapped
    • Generalizability of phospho-degron logic to other substrates not tested here
  10. 2019 Medium

    Implicated the PELI1 RING domain in ER-stress signaling through direct Hsp90 binding that enhances IRE1α phosphorylation in cardiac endothelium.

    Evidence Domain-level Co-IP, endothelial-specific KO, IRE1α phosphorylation and permeability assays in diabetic mice

    PMID:31260751

    Open questions at the time
    • Mechanistic link from Hsp90 binding to IRE1α activation not reconstituted
    • Ubiquitination role, if any, undefined
  11. 2020 High

    Placed PELI1 in metabolic reprogramming by non-degradative ubiquitination of TSC1 that stabilizes TSC1-TSC2 and inhibits mTORC1, controlling T cell glycolysis and antitumor immunity.

    Evidence Ubiquitination assays, TSC1-TSC2 Co-IP, mTORC1 readouts in KO T cells, tumor models

    PMID:33215753

    Open questions at the time
    • TSC1 ubiquitination site/linkage not mapped
    • How non-degradative chains promote dimerization unresolved
  12. 2020 High

    Linked PELI1 to neurodegeneration by degrading C/EBPβ to limit CD36 and microglial Aβ phagocytosis, identifying a transcription-factor substrate in the CNS.

    Evidence Co-IP, ubiquitination assay, Peli1-KO microglia, 5×FAD model, phagocytosis assays

    PMID:33017390

    Open questions at the time
    • C/EBPβ ubiquitination site not mapped
    • Direct vs indirect CD36 regulation not fully separated
  13. 2021 High

    Showed PELI1 activates the NLRP3 inflammasome specifically by K63 ubiquitination of ASC-K55, promoting ASC oligomerization and IL-1β maturation.

    Evidence K55 mutagenesis, ASC-NLRP3 Co-IP, oligomerization assays, KO mice with multiple inflammasome inducers

    PMID:34706239

    Open questions at the time
    • Basis for NLRP3 selectivity over other inflammasomes unresolved
    • Upstream signal triggering ASC ubiquitination unclear
  14. 2021 Medium

    Positioned PELI1 upstream of Tfh differentiation via c-Rel/ICOS/PI3K-AKT/Klf2, integrating its NF-κB control with T cell fate.

    Evidence Bone marrow chimeras, flow cytometry, PI3K-AKT assays, Klf2 reconstitution rescue, Peli1-KO mice

    PMID:33707688

    Open questions at the time
    • No direct ubiquitination substrate in this axis identified
    • ICOS regulation shown as downstream of c-Rel, not direct
  15. 2021 Medium

    Confirmed the PELI1–NIK–noncanonical NF-κB axis in cancer, where NIK degradation lowers Bclxl and sensitizes esophageal cancer cells to radiation.

    Evidence Ubiquitination/stability assays, noncanonical NF-κB reporters, PELI1 KD/KO, in vivo irradiation model

    PMID:34738714

    Open questions at the time
    • Single-lab confirmation of NIK axis in cancer context
    • NIK ubiquitination site not mapped
  16. 2022 High

    Extended PELI1 to autophagy regulation by RING-domain-dependent K63 ubiquitination of P62-K7 that blocks P62 dimerization and autophagic flux in cardiac I/R.

    Evidence Co-IP, GST-pulldown, K7 mutagenesis, LC3/P62 flux assays, KO mice with I/R model

    PMID:36179399

    Open questions at the time
    • Effect on broader autophagy machinery not assessed
    • Tissue specificity of P62 targeting unclear
  17. 2023 Medium

    Identified PELI1 as a driver of macrophage M1 polarization through K63 ubiquitination and nuclear translocation of IRF5 in cardiac I/R injury.

    Evidence Ubiquitination assays, IRF5 nuclear fractionation, macrophage-specific KO, I/R model, M1/M2 flow cytometry

    PMID:36822176

    Open questions at the time
    • IRF5 ubiquitination site not mapped
    • Single-lab finding
  18. 2023 Medium

    Revealed a PELI1-EGFR positive feedback loop where EGFR phosphorylates and activates PELI1, which K63-ubiquitinates and stabilizes EGFR to promote breast cancer metastasis.

    Evidence Co-IP, phospho-site mapping (Y154/T264), K63 linkage assays, migration/invasion and metastasis models

    PMID:36841821

    Open questions at the time
    • EGFR ubiquitination site not mapped
    • Single-lab reciprocal regulation model
  19. 2023 Medium

    Connected cardiomyocyte PELI1 to fibrosis through NF-κB/AP-1-driven miR-494-3p in exosomes that activate fibroblasts via PTEN suppression.

    Evidence CM-conditional KO mice, miRNA array, exosome isolation, NF-κB/AP-1 reporters, PTEN/AKT assays

    PMID:36520055

    Open questions at the time
    • No direct ubiquitination substrate in this axis
    • Single-lab exosomal mechanism
  20. 2024 High

    Expanded PELI1's substrate repertoire to metabolic transcription factor HNF4α (K307/K309) in heart, linking its activity to fatty acid oxidation and cardiac hypertrophy.

    Evidence Co-IP, mass spectrometry, K307/K309 mutagenesis, RNA-seq, AAV9-HNF4α rescue, TAC model

    PMID:38346961

    Open questions at the time
    • Ubiquitin linkage type not specified
    • Single-lab cardiac context
  21. 2024 Medium

    Identified Foxp1 degradation as the mechanism by which PELI1 promotes IL-6-driven macrophage activation and pulmonary vascular remodeling.

    Evidence Proteomics, Co-IP, Foxp1 stability assays, myeloid Peli1/Foxp1 KO mice, hypoxia PH model

    PMID:39618410

    Open questions at the time
    • Foxp1 ubiquitination site/linkage not mapped
    • Partial epistasis suggests additional substrates
  22. 2024 Medium

    Showed FHA-dependent K48 ubiquitination of RPS3 by PELI1 activates PI3K/Akt/GSK3β and weakens RPS3-mediated p53 protection in pancreatic cancer.

    Evidence Co-IP, GST-pulldown, ubiquitination assays, immunofluorescence, xenograft and metastasis models

    PMID:38528516

    Open questions at the time
    • RPS3 ubiquitination site not mapped
    • Single-lab finding
  23. 2024 Medium

    Added IRAK2 as a K63-ubiquitination target whose degradation underlies PELI1's anti-inflammatory effect in airway epithelium via p38-MAPK/NF-κB suppression.

    Evidence CRISPR KO, AAV6.2 overexpression, ubiquitination assays, IRAK2 re-expression rescue, MAPK/NF-κB assays

    PMID:40986758

    Open questions at the time
    • IRAK2 ubiquitination site not mapped
    • K63-degradative mechanism atypical and not reconstituted
  24. 2024 Low

    Placed PELI1 upstream of TCF-1 in CD4+ T cell lineage choice through ubiquitination-mediated TCF-1 degradation.

    Evidence Co-IP, ubiquitination assays, TCF-1 rescue, T cell subset flow cytometry

    PMID:39617092

    Open questions at the time
    • TCF-1 ubiquitination site and chain type not mapped
    • Single-lab, mechanism not reconstituted
  25. 2024 Medium

    Identified INPP5J as a degradative target supporting PELI1's pro-tumorigenic role in pancreatic cancer.

    Evidence Co-IP, ubiquitination assays, gain/loss-of-function, xenograft, INPP5J rescue

    PMID:38685520

    Open questions at the time
    • INPP5J ubiquitination site/linkage not mapped
    • Single-lab finding
  26. 2025 Medium

    Linked PELI1 to atherosclerosis through K48 degradation of YB-1 limiting NLRP3 activation, and showed METTL3/YTHDC2 m6A control of Peli1 mRNA, adding an upstream regulatory layer.

    Evidence Ubiquitination assays, YB-1 stability, m6A and YTHDC2 co-precipitation, atherosclerosis model with rescue

    PMID:40102597

    Open questions at the time
    • YB-1 ubiquitination site not mapped
    • Single-lab m6A regulatory mechanism
  27. 2025 Low

    Implicated PELI1 in microglial exosome release driving neurotoxic astrocyte conversion, with a feedback loop upregulating microglial Peli1.

    Evidence Microglial depletion, exosome blockade, exosome injection, Peli1 inhibition, astrocyte phenotyping

    PMID:40816423

    Open questions at the time
    • Direct biochemical mechanism by which PELI1 controls exosome release not characterized
    • Single-lab functional inference
  28. 2026 Low

    Connected PELI1 to ferroptosis via FTH1 degradation in a P53/PELI1/FTH1 axis activated by hyperandrogenism in PCOS.

    Evidence Transcriptome sequencing, cellular ubiquitination assays, PCOS mouse model, deferoxamine rescue

    PMID:41620040

    Open questions at the time
    • FTH1 ubiquitination inferred, not fully reconstituted
    • Mechanistic chain from p53 to PELI1 not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PELI1 selects among activating K63 versus degradative K48 chemistry on different substrates, and what governs its tissue-specific substrate repertoire, remains unresolved.
  • No structural model explaining linkage-type switching
  • Substrate-specificity determinants beyond FHA phospho-recognition undefined
  • Upstream signals dictating context-specific substrate choice unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0016874 ligase activity 8 GO:0016740 transferase activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3
Pathway
R-HSA-168256 Immune System 7 R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-1430728 Metabolism 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 1
Partners
ASCEGFRMDMXNIKRIPK1RIPK3TRAF3TSC1

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 Peli1 (E3 ubiquitin ligase) binds to and ubiquitinates RIP1, mediating K63-linked ubiquitination to promote IKK activation downstream of the TLR3/TLR4 adaptor TRIF, but is dispensable for IKK-NF-κB activation by MyD88-dependent TLRs and IL-1R. Co-immunoprecipitation, in vitro ubiquitination assay, genetic knockout mice, cytokine induction assays Nature immunology High 19734906
2011 Peli1 mediates K48-linked ubiquitination of c-Rel (NF-κB family member), targeting it for degradation; Peli1 deficiency causes nuclear accumulation of c-Rel and hyperactivation of T cells, leading to spontaneous autoimmunity. Genetic knockout mice, ubiquitination assays, nuclear fractionation/immunoblot, T cell activation assays Nature immunology High 21874024
2013 Peli1 promotes degradation of TRAF3 (a potent inhibitor of MAPK activation) in microglia via ubiquitin-mediated proteolysis, thereby enabling TLR pathway-driven chemokine and cytokine induction; ablation of TRAF3 restores microglial activation in Peli1-deficient mice. Genetic knockout mice, EAE model, TRAF3 protein level analysis, epistasis rescue experiment (Traf3 ablation in Peli1-KO) Nature medicine High 23603814
2017 PELI1 mediates K63-linked ubiquitination of RIPK1 at lysine 115 in a kinase-activity-dependent manner during necroptosis, promoting necrosome formation (RIPK1-RIPK3 interaction) and RIPK3/MLKL activation; separately, PELI1 maintains c-FLIP mRNA levels, and its deficiency sensitizes cells to apoptosis. Ubiquitination assays with site-directed mutagenesis (K115), co-immunoprecipitation of RIPK1-RIPK3, RIPK1 kinase inhibitor experiments, knockout cell lines and mice Proceedings of the National Academy of Sciences of the United States of America High 29078411
2018 PELI1 selectively targets kinase-active RIP3 (phosphorylated on T182) for K48-linked polyubiquitylation at K363 via interaction with the PELI1 FHA domain, leading to proteasome-dependent RIP3 degradation and prevention of necroptosis triggered by RIP3 hyperactivation. Co-immunoprecipitation, in vitro ubiquitination assay, site-directed mutagenesis (T182, K363), proteasome inhibitor experiments, patient TEN keratinocyte samples Molecular cell High 29883609 30269743
2018 Peli1 functions as an E3 ligase for NF-κB-inducing kinase (NIK), mediating K48-linked ubiquitination and proteasomal degradation of NIK, thereby suppressing noncanonical NF-κB signaling in B cells and restraining autoantibody production in lupus-like disease. Co-immunoprecipitation, ubiquitination assays, B cell-specific conditional knockout mice, lupus disease model Nature communications High 29555915
2018 Peli1 binds Mdmx in vitro and in vivo and promotes non-degradative ubiquitination of Mdmx, causing its cytoplasmic localization; Peli1 loss or knockdown induces nuclear localization of Mdmx and suppresses p53 activity, and Peli1-null mice show accelerated Myc-induced tumorigenesis associated with reduced p53 function. Co-immunoprecipitation, in vitro binding assay, ubiquitination assay, subcellular fractionation, Peli1-knockout mice with Myc-driven tumor model Cancer research High 29523541
2019 Peli1 FHA domain binds to phosphorylated HPD (T382 phosphorylated by STK33) and mediates polyubiquitylation and degradation of HPD; TTC36 competes with STK33 to reduce HPD phosphorylation and thus prevents Peli1 recruitment and HPD degradation. Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, Ttc36 knockout mice with tyrosinemia phenotype Nature communications High 31537781
2019 Peli1 Ring domain directly binds Hsp90, and this interaction enhances IRE1α phosphorylation in cardiac microvascular endothelial cells, promoting ER stress and microvascular injury; Peli1 deficiency in endothelial cells alleviates diabetes-induced cardiac microvascular permeability. Co-immunoprecipitation (Ring domain-Hsp90), endothelial cell-specific Peli1 knockout, IRE1α phosphorylation assays, permeability assays in diabetic mouse model Biochimica et biophysica acta. Molecular basis of disease Medium 31260751
2020 Peli1 mediates non-degradative ubiquitination of TSC1, promoting TSC1-TSC2 dimerization and TSC2 stabilization, thereby inhibiting mTORC1 activity; Peli1 ablation in T cells markedly increases glycolysis via mTORC1 activation and enhances antitumor immunity. Ubiquitination assays, Co-immunoprecipitation of TSC1-TSC2, mTORC1 activity assays, Peli1-knockout T cells, tumor models The EMBO journal High 33215753
2020 Peli1 directly ubiquitinates C/EBPβ (a transcription factor for scavenger receptor CD36), promoting its degradation; Peli1 loss increases C/EBPβ protein levels and CD36 expression, enhancing microglial Aβ phagocytosis and reducing Aβ deposition in 5×FAD mice. Co-immunoprecipitation, ubiquitination assay, Peli1-knockout microglia, 5×FAD mouse model, phagocytosis assays PLoS biology High 33017390
2021 Peli1 conjugates K63-linked ubiquitin chains onto lysine 55 of ASC (inflammasome adaptor), facilitating ASC/NLRP3 interaction and ASC oligomerization, thereby promoting NLRP3 inflammasome activation and IL-1β maturation; this is specific to NLRP3 (not Aim2, NLRP1, or NLRC4 inflammasomes). Ubiquitination assays with site-directed mutagenesis (K55 of ASC), co-immunoprecipitation (ASC-NLRP3), ASC oligomerization assays, Peli1-knockout mice with peritonitis/LPS shock models Cell reports High 34706239
2021 Peli1 deficiency promotes c-Rel-mediated inducible T-cell costimulator (ICOS) expression; increased ICOS activates PI3K-AKT signaling, suppressing Klf2 expression to promote T follicular helper (Tfh) cell differentiation; reconstitution of Klf2 abolishes the Tfh differentiation difference between WT and Peli1-KO cells. Bone marrow chimeric experiments, flow cytometry, PI3K-AKT signaling assays, Klf2 reconstitution rescue experiments, Peli1-KO mice Cellular & molecular immunology Medium 33707688
2021 PELI1 mediates K48-linked polyubiquitination and proteasomal degradation of NF-κB-inducing kinase (NIK), thereby inhibiting noncanonical NF-κB pathway activation and reducing Bclxl expression, which sensitizes esophageal squamous cancer cells to ionizing radiation-induced apoptosis. Ubiquitination assays, NIK protein stability assays, noncanonical NF-κB reporter assays, PELI1 KD/KO in cancer cells, in vivo tumor irradiation model Molecular oncology Medium 34738714
2022 Peli1 (via its Ring domain) directly interacts with P62/sequestosome-1 and promotes K63-linked ubiquitination of P62 at K7, inhibiting P62 dimerization and autophagic degradation, thereby impairing autophagy flux during myocardial ischemia/reperfusion injury. Co-immunoprecipitation, GST-pulldown, in vitro ubiquitination with site mutagenesis (K7), LC3/P62 flux assays, Peli1-KO mice with I/R model Journal of molecular and cellular cardiology High 36179399
2023 Peli1 promotes K63-linked ubiquitination and nuclear translocation of IRF5 in macrophages, driving M1 polarization; Peli1 deficiency in macrophages reduces IRF5 nuclear translocation, suppresses M1 polarization, and alleviates myocardial ischemia/reperfusion injury. Ubiquitination assays, nuclear fractionation for IRF5, macrophage-specific Peli1 conditional knockout, I/R mouse model, flow cytometry for M1/M2 markers Journal of leukocyte biology Medium 36822176
2024 Peli1 binds HNF4α via its RING-like domain and promotes HNF4α ubiquitination at residues K307 and K309, leading to HNF4α degradation, reduced fatty acid oxidation gene expression, and exacerbated cardiac hypertrophy; HNF4α inhibition abolishes the cardioprotective effect of Peli1 knockout. Co-immunoprecipitation, mass spectrometry, ubiquitination assay with K307/K309 mutagenesis, RNA-seq, FAO stress assay, rAAV9-HNF4α delivery, Peli1 KO mice with TAC model Cell death & disease High 38346961
2024 Peli1 facilitates ubiquitination and proteasomal degradation of Foxp1 in macrophages, relieving Foxp1-mediated transcriptional inhibition of IL-6, thus promoting macrophage activation and IL-6-driven pulmonary vascular remodeling; myeloid Foxp1 deficiency partially eliminates the protective effect of myeloid Peli1 deficiency in pulmonary hypertension. Proteomic analysis, co-immunoprecipitation, Foxp1 stability assays, myeloid-specific Peli1-KO and Foxp1-KO mice, hypoxia-induced PH model, IL-6 transcription assays Hypertension Medium 39618410
2024 PELI1 interacts with Ribosomal Protein S3 (RPS3) through its FHA domain and promotes K48-linked polyubiquitination and degradation of RPS3, which activates the PI3K/Akt/GSK3β signaling pathway and reduces RPS3-mediated protection of p53 from MDM2-dependent degradation, thereby promoting pancreatic cancer progression. Co-immunoprecipitation, GST-pulldown, ubiquitination assays, immunofluorescence co-localization, in vivo xenograft and liver metastasis models Journal of experimental & clinical cancer research Medium 38528516
2024 PELI1 mediates K63-linked ubiquitination and degradation of IRAK2 in airway epithelial cells; IRAK2 overexpression reverses the anti-inflammatory effect of PELI1 overexpression by activating p38-MAPK/NF-κB signaling. CRISPR/Cas9 KO, AAV6.2 overexpression in vivo, ubiquitination assays, epistasis rescue (IRAK2 re-expression), MAPK/NF-κB signaling assays American journal of respiratory cell and molecular biology Medium 40986758
2023 Peli1 promotes miR-494-3p expression via NF-κB/AP-1 transcriptional activation in cardiomyocytes under mechanical stretch; cardiomyocyte-derived exosomes enriched with miR-494-3p activate cardiac fibroblasts by targeting PTEN, amplifying AKT, SMAD2/3, and ERK phosphorylation, thereby contributing to cardiac fibrosis. CM-conditional Peli1 knockout mice, miRNA microarray, exosome isolation, NF-κB/AP-1 reporter assays, PTEN/AKT pathway assays in cardiac fibroblasts FASEB journal Medium 36520055
2025 PELI1 mediates K48-linked ubiquitination and degradation of YB-1 in macrophages, preventing NLRP3 inflammasome activation; YTHDC2-recognized m6A modification of Peli1 mRNA (mediated by METTL3) promotes Peli1 mRNA degradation, reducing Peli1 protein levels during atherosclerosis. Ubiquitination assays, YB-1 stability assays, m6A methylation assay, YTHDC2 co-precipitation, in vivo atherosclerosis model with rescue experiments Communications biology Medium 40102597
2023 PELI1 interacts with EGFR; EGFR activation phosphorylates PELI1 at Tyr154 and Thr264, activating its E3 ubiquitin ligase activity; reciprocally, PELI1 promotes K63-linked polyubiquitination of EGFR to enhance EGFR stability, creating a positive feedback loop that promotes breast cancer metastasis. Co-immunoprecipitation, phospho-site mapping, ubiquitination assays, K63-linkage specific assays, breast cancer cell migration/invasion assays, in vivo metastasis model Oncogenesis Medium 36841821
2024 PELI1 interacts with INPP5J via Co-immunoprecipitation and promotes ubiquitination and proteasomal degradation of INPP5J in pancreatic cancer cells; INPP5J overexpression reverses the pro-tumorigenic effects of PELI1 overexpression. Co-immunoprecipitation, ubiquitination assays, gain/loss-of-function experiments, xenograft model, epistasis rescue with INPP5J overexpression Cellular signalling Medium 38685520
2025 Peli1 is identified as a key regulator of microglial exosome release; Peli1 inhibition reduces microglial activation and the generation of proinflammatory exosomes that drive neurotoxic astrocyte conversion; a feedback loop was identified where neurotoxic astrocytes upregulate Peli1 expression in microglia. PLX3397 microglial depletion, GW4869 exosome secretion blockade, purified exosome injection in vivo, Peli1 inhibition in microglia, astrocyte phenotype assays Pharmacological research Low 40816423
2015 Peli1 negatively regulates type I interferon (IFN-β) induction in microglia in response to TLR ligands and vesicular stomatitis virus; Peli1-deficient mice show heightened CNS IFN-I responses and reduced brain viral titers after intranasal VSV infection. Peli1 genetic knockout mice, intranasal VSV infection, IFN-β measurement in microglia in vitro and CNS in vivo, viral titer assay Cell & bioscience Medium 26131354
2026 PELI1 promotes ubiquitination and degradation of FTH1 (ferritin heavy chain) in ovarian granulosa cells, contributing to ferroptosis; the P53/PELI1/FTH1 pathway is activated by hyperandrogenism in PCOS, and iron death inhibitor deferoxamine alleviates follicular development disorders. Transcriptome sequencing, cellular ubiquitination assays, PCOS mouse model, iron death inhibitor rescue experiments The Journal of steroid biochemistry and molecular biology Low 41620040
2024 PELI1 interacts with TCF-1 and promotes its ubiquitination and degradation; inhibition of TCF-1 reduces the effects of PELI1 knockdown on CD4+ T cell differentiation toward Th2 and Treg cells, placing PELI1 upstream of TCF-1 in T cell lineage decisions. Co-immunoprecipitation, ubiquitination assays, TCF-1 rescue experiments, flow cytometry for T cell subsets Experimental cell research Low 39617092

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Peli1 facilitates TRIF-dependent Toll-like receptor signaling and proinflammatory cytokine production. Nature immunology 215 19734906
2013 Peli1 promotes microglia-mediated CNS inflammation by regulating Traf3 degradation. Nature medicine 167 23603814
2011 The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity. Nature immunology 162 21874024
2017 PELI1 functions as a dual modulator of necroptosis and apoptosis by regulating ubiquitination of RIPK1 and mRNA levels of c-FLIP. Proceedings of the National Academy of Sciences of the United States of America 99 29078411
2018 PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylation-Dependent Proteasomal Degradation. Molecular cell 94 29883609
2018 Peli1 negatively regulates noncanonical NF-κB signaling to restrain systemic lupus erythematosus. Nature communications 66 29555915
2021 Peli1 facilitates NLRP3 inflammasome activation by mediating ASC ubiquitination. Cell reports 54 34706239
2016 A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells. The Journal of experimental medicine 54 27481129
2022 MiR-30c-5p loss-induced PELI1 accumulation regulates cell proliferation and migration via activating PI3K/AKT pathway in papillary thyroid carcinoma. Journal of translational medicine 39 34991623
2023 Cardiomyocyte-specific Peli1 contributes to the pressure overload-induced cardiac fibrosis through miR-494-3p-dependent exosomal communication. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 36520055
2017 Peli1 Contributions in Microglial Activation, Neuroinflammatory Responses and Neurological Deficits Following Experimental Subarachnoid Hemorrhage. Frontiers in molecular neuroscience 38 29249938
2018 Peli1 facilitates virus replication and promotes neuroinflammation during West Nile virus infection. The Journal of clinical investigation 37 30247157
2024 BMSCs-derived exosomes inhibit macrophage/microglia pyroptosis by increasing autophagy through the miR-21a-5p/PELI1 axis in spinal cord injury. Aging 34 38466640
2020 Methamphetamine induced neuroinflammation in mouse brain and microglial cell line BV2: Roles of the TLR4/TRIF/Peli1 signaling axis. Toxicology letters 31 32768653
2020 Peli1 impairs microglial Aβ phagocytosis through promoting C/EBPβ degradation. PLoS biology 31 33017390
2019 Peli1 induction impairs cardiac microvascular endothelium through Hsp90 dissociation from IRE1α. Biochimica et biophysica acta. Molecular basis of disease 30 31260751
2019 HPD degradation regulated by the TTC36-STK33-PELI1 signaling axis induces tyrosinemia and neurological damage. Nature communications 29 31537781
2021 The ubiquitin ligase Peli1 inhibits ICOS and thereby Tfh-mediated immunity. Cellular & molecular immunology 28 33707688
2020 Inhibition of Glycolysis in Pathogenic TH17 Cells through Targeting a miR -21-Peli1-c-Rel Pathway Prevents Autoimmunity. Journal of immunology (Baltimore, Md. : 1950) 27 32414810
2020 The E3 ubiquitin ligase Peli1 regulates the metabolic actions of mTORC1 to suppress antitumor T cell responses. The EMBO journal 25 33215753
2023 Polyguluronic acid alleviates doxorubicin-induced cardiotoxicity by suppressing Peli1-NLRP3 inflammasome-mediated pyroptosis. Carbohydrate polymers 24 37739547
2021 Transforming Growth Factor-β1 Promotes M1 Alveolar Macrophage Polarization in Acute Lung Injury by Up-Regulating DNMT1 to Mediate the microRNA-124/PELI1/IRF5 Axis. Frontiers in cellular and infection microbiology 22 34504806
2020 Peli1 signaling blockade attenuates congenital zika syndrome. PLoS pathogens 22 32544190
2020 MiR-153-3p induces immune dysregulation by inhibiting PELI1 expression in umbilical cord-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Autoimmunity 19 32321315
2019 MiR-142a-3p and miR-155-5p reduce methamphetamine-induced inflammation: Role of the target protein Peli1. Toxicology and applied pharmacology 18 30914375
2018 Peli1 Modulates the Subcellular Localization and Activity of Mdmx. Cancer research 18 29523541
2015 Peli1 negatively regulates type I interferon induction and antiviral immunity in the CNS. Cell & bioscience 18 26131354
2023 Decreased Peli1 expression attenuates osteoarthritis by protecting chondrocytes and inhibiting M1-polarization of macrophages. Bone & joint research 16 36718653
2023 Peli1 deletion in macrophages attenuates myocardial ischemia/reperfusion injury by suppressing M1 polarization. Journal of leukocyte biology 16 36822176
2019 Peli1 controls the survival of dopaminergic neurons through modulating microglia-mediated neuroinflammation. Scientific reports 16 31142803
2022 Peli1 contributes to myocardial ischemia/reperfusion injury by impairing autophagy flux via its E3 ligase mediated ubiquitination of P62. Journal of molecular and cellular cardiology 14 36179399
2021 PELI1 promotes radiotherapy sensitivity by inhibiting noncanonical NF-κB in esophageal squamous cancer. Molecular oncology 14 34738714
2025 Exosome-mediated microglia-astrocyte interactions drive neuroinflammation in Parkinson's disease with Peli1 as a potential therapeutic target. Pharmacological research 13 40816423
2022 The E3 Ubiquitin Ligase Peli1 Deficiency Promotes Atherosclerosis Progression. Cells 13 35805095
2022 Palmitic Acid Promotes Lung Metastasis of Melanomas via the TLR4/TRIF-Peli1-pNF-κB Pathway. Metabolites 12 36422271
2016 The Brain Proteome of the Ubiquitin Ligase Peli1 Knock-Out Mouse during Experimental Autoimmune Encephalomyelitis. Journal of proteomics & bioinformatics 12 27746629
2011 Peli1 (rel)ieves autoimmunity. Nature immunology 12 21934671
2024 PELI1: key players in the oncogenic characteristics of pancreatic Cancer. Journal of experimental & clinical cancer research : CR 11 38528516
2024 Peli1 Deficiency in Macrophages Attenuates Pulmonary Hypertension by Enhancing Foxp1-Mediated Transcriptional Inhibition of IL-6. Hypertension (Dallas, Tex. : 1979) 11 39618410
2023 Regulatory T Cells Overexpressing Peli1 Show Better Efficacy in Repairing Ovarian Endocrine Function in Autoimmune Premature Ovarian Insufficiency. Laboratory investigation; a journal of technical methods and pathology 10 37039145
2023 Resveratrol-derived inhibitors of the E3 ubiquitin ligase PELI1 inhibit the metastasis of triple-negative breast cancer. European journal of medicinal chemistry 10 38150964
2021 MiR-301a-3p Advances IRAK1-Mediated Differentiation of Th17 Cells to Promote the Progression of Systemic Lupus Erythematosus via Targeting PELI1. Journal of healthcare engineering 10 34931135
2024 HNF4α ubiquitination mediated by Peli1 impairs FAO and accelerates pressure overload-induced myocardial hypertrophy. Cell death & disease 9 38346961
2023 Role of the Peli1-RIPK1 Signaling Axis in Methamphetamine-Induced Neuroinflammation. ACS chemical neuroscience 9 36763609
2023 PELI1 and EGFR cooperate to promote breast cancer metastasis. Oncogenesis 9 36841821
2025 Peli1, regulated by m6A modification, suppresses NLRP3 inflammasome activation in atherosclerosis by inhibiting YB-1. Communications biology 7 40102597
2018 Poly IC pretreatment suppresses B cell-mediated lupus-like autoimmunity through induction of Peli1. Acta biochimica et biophysica Sinica 7 30032173
2025 MiR-21-5p promotes RPE cell necroptosis by targeting Peli1 in a rat model of AMD. In vitro cellular & developmental biology. Animal 4 40588681
2024 PELI1 overexpression contributes to pancreatic cancer progression through upregulating ubiquitination-mediated INPP5J degradation. Cellular signalling 4 38685520
2021 Immune-related genes STIM1, ITPKC and PELI1 polymorphisms are associated with risk of colorectal cancer. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 4 33470690
2022 Bcl-6-dependent risk stratification by nuclear expression of Peli1 in diffuse large B-cell lymphoma. Journal of Cancer 3 36606193
2018 Regulation of RIP3 protein stability by PELI1-mediated proteasome-dependent degradation. BMB reports 3 30269743
2023 Aberrant expression of PELI1 caused by Jagged1 accelerates the malignant phenotype of pancreatic cancer. Cellular signalling 2 37657587
2026 IRAK2 ubiquitination mediated by PELI1 regulates airway epithelial function and alleviates pediatric asthma. American journal of respiratory cell and molecular biology 1 40986758
2025 hsa_circ_0004846 enhances the malignant phenotype of papillary thyroid carcinoma cells via the miR‑142‑3p/PELI1 axis. Oncology letters 1 40070794
2025 PELI1 silencing delays intervertebral disc degeneration by impeding nucleus pulposus cell death. Connective tissue research 1 40407238
2025 Adipose-derived MSC extracellular vesicles ameliorate sepsis by reprogramming macrophages via miR-21-5p targeting PELI1. Biomolecules & biomedicine 1 41143725
2026 miR-369-3p Regulates Microglia Polarization and Neuroinflammation in Traumatic Spinal Cord Injury by Targeting PELI1. Global spine journal 0 41481033
2026 PELI1 in human cancers: a pan-cancer exploration of its molecular function, clinical significance, and immunomodulatory roles. Frontiers in immunology 0 41562077
2026 E3 ubiquitin ligase PELI1 promotes ferroptosis in granulosa cells in PCOS by degrading Fth1. The Journal of steroid biochemistry and molecular biology 0 41620040
2024 Knockdown of PELI1 promotes Th2 and Treg cell differentiation in juvenile idiopathic arthritis. Experimental cell research 0 39617092

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