Affinage

FBXO11

F-box only protein 11 · UniProt Q86XK2

Length
927 aa
Mass
103.6 kDa
Annotated
2026-06-09
69 papers in source corpus 32 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FBXO11 is the substrate-recognition subunit of an SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase that selects diverse regulatory proteins for ubiquitylation and proteasomal degradation, thereby controlling germinal-center B-cell biology, epithelial-mesenchymal transition (EMT), cell-cycle exit, hematopoietic differentiation, and immune output (PMID:22113614, PMID:23478441, PMID:33156908). Its best-established target is the transcriptional repressor BCL6: SCF-FBXO11 directly ubiquitylates BCL6 for degradation, tumor-derived mutants fail to do so, and germinal-center-specific knockout elevates BCL6 and expands GC B cells, defining FBXO11 as a haploinsufficient tumor suppressor in B-cell lymphoma that cooperates with MYC (PMID:22113614, PMID:27166359, PMID:34625792). FBXO11 enforces an anti-EMT program by degrading SNAIL family members (SNAI1, SNAI2/Slug, Scratch) and ZEB1, with SNAIL recognition gated by PKD1 phosphorylation; loss causes SNAIL/ZEB1 accumulation, invasion, and metastasis (PMID:25203322, PMID:25827072, PMID:39409891). The ligase also degrades the CRL4 receptor CDT2 to time cell-cycle exit and stabilize p21/Set8 for TGF-β control (PMID:23478441, PMID:23478445), the H3K27me3 reader BAHD1 to permit GATA1-dependent erythroid maturation (PMID:33156908), the MHC-II master regulator CIITA to dampen antigen presentation (PMID:36179686, PMID:37279268), and additional substrates including hnRNPA2B1, NPM1, KIF2C, Fosl2, and β-catenin (PMID:37837399, PMID:41542766, PMID:40447129, PMID:39581215, PMID:39309441). Beyond canonical K48-linked degradation, FBXO11 acts as an adaptor promoting NEDD8 conjugation of p53 to repress its transcriptional activity (PMID:17098746) and catalyzes K63-linked ubiquitylation of TRAF3 and of cytosolic LONP1, the latter promoting LONP1 mitochondrial import and electron-transport-chain Complex IV assembly (PMID:36977592, PMID:41289019). Mutation of Fbxo11 in mice (the Jeff allele) causes epithelial defects of the middle ear and palate linked to elevated phospho-Smad2 and reduced p53 (PMID:17035249, PMID:19580641, PMID:26471094), and FBXO11 loss disrupts neuronal differentiation and migration in iPSC and Drosophila models (PMID:40114442).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2006 Medium

    Established the first biochemical activities of FBXO11: that beyond SCF membership it acts as an adaptor promoting p53 neddylation to repress p53, and that it carries an arginine methyltransferase domain (PRMT9) with in vitro activity.

    Evidence In vitro neddylation and methyltransferase assays, p53 reporter assays, mutagenesis of p53 lysines, mass spectrometry of methylation products

    PMID:16487488 PMID:17098746

    Open questions at the time
    • Methyltransferase activity not validated by domain mutagenesis or in cells
    • Physiological relevance of p53 neddylation versus FBXO11's ligase function unclear
  2. 2006 Medium

    Linked FBXO11 to mammalian development via the Jeff mouse, showing it is required for epithelial development of the middle ear and palate.

    Evidence Positional cloning, mutant mouse characterization, tissue expression by IHC/in situ hybridization

    PMID:17035249

    Open questions at the time
    • Molecular substrate underlying the epithelial phenotype not defined
    • Mechanism beyond F-box membership not biochemically established
  3. 2009 Medium

    Connected the Jeff epithelial phenotype to dysregulated TGF-β signaling, showing Fbxo11 limits phospho-Smad2 nuclear accumulation indirectly through p53 stabilization rather than direct Smad2 binding.

    Evidence Immunohistochemistry, negative tissue Co-IP, Jeff/Smad2 double-heterozygote genetic epistasis, p53 protein measurement

    PMID:19580641

    Open questions at the time
    • No direct FBXO11-Smad2 interaction
    • Mechanism by which p53 limits pSmad2 unresolved
  4. 2012 High

    Defined FBXO11's flagship function: SCF-FBXO11 directly ubiquitylates BCL6 for degradation, and tumor mutations abolish this, establishing FBXO11 as a tumor suppressor in DLBCL.

    Evidence Co-IP, ubiquitylation assays, reconstitution in FBXO11-deleted DLBCL lines, mutagenesis of disease alleles, xenograft suppression

    PMID:22113614

    Open questions at the time
    • Degron/recognition motif on BCL6 not mapped
    • Upstream signals controlling BCL6 recognition not defined here
  5. 2013 High

    Revealed that FBXO11 degrades the CRL4 receptor CDT2 through an atypical phospho-inhibited degron, coupling FBXO11 to cell-cycle exit timing and TGF-β output via p21/Set8 stabilization.

    Evidence AP-MS, reciprocal Co-IP, ubiquitylation assays, phospho-mutant analysis, cycloheximide chase, C. elegans genetics, TGF-β and migration assays

    PMID:23478441 PMID:23478445

    Open questions at the time
    • Kinase responsible for the inhibitory CDT2 phosphorylation only partially defined
    • Quantitative contribution of CDT2 versus other substrates to TGF-β output unclear
  6. 2014 High

    Showed FBXO11 enforces an anti-EMT program by degrading phospho-SNAIL downstream of PKD1, and confirmed conserved DRE-1/FBXO11 degradation of the BLIMP-1 transcription factor controlling developmental timing.

    Evidence Genome-wide siRNA screen, Co-IP, ubiquitylation assays, phospho-degron mutagenesis, breast cancer metastasis models; C. elegans epistasis and protein stability assays

    PMID:24613396 PMID:25203322

    Open questions at the time
    • Whether all SNAIL family recognition requires phosphorylation unresolved at this stage
    • Tissue specificity of SNAIL versus BLIMP-1 targeting not addressed
  7. 2015 High

    Generalized SNAIL-family control by FBXO11, showing phosphorylation-independent degradation of SNAI1/SNAI2/Scratch in vivo, and added an indirect role in destabilizing HIF-1α mRNA.

    Evidence Co-IP, ubiquitylation assays, FBXO11 knockout mice with epidermal Snail accumulation, C. elegans epistasis; siRNA, mRNA stability assay and F-box deletion mutant for HIF-1α

    PMID:25827072 PMID:26187670

    Open questions at the time
    • Reconciliation of phosphorylation-dependent versus -independent SNAIL recognition
    • Identity of the FBXO11 substrate controlling HIF-1α mRNA stability unknown
  8. 2015 Medium

    Strengthened the FBXO11-p53 axis by demonstrating direct physical interaction in vivo abolished by the Jeff mutation, placing p53 epistatically upstream of TGF-β pathway control in epithelial development.

    Evidence Tissue Co-IP from embryonic lung, p53 KO and Jeff/p53 double-heterozygote genetic epistasis, pSMAD2 immunofluorescence

    PMID:26471094

    Open questions at the time
    • Whether FBXO11 stabilizes or modifies p53 in this context not biochemically resolved
    • Single lab
  9. 2016 High

    Provided physiological proof that FBXO11 controls BCL6 in vivo during the germinal-center reaction, with loss driving lymphoproliferation.

    Evidence GC-specific conditional FBXO11 knockout mice, flow cytometry, immunofluorescence, BCL6 stability assays

    PMID:27166359

    Open questions at the time
    • Whether BCL6 is the sole relevant substrate in GC B cells not excluded
  10. 2017 Medium

    Attempted a structural explanation for substrate selection, showing the UBR-box of FBXO11 lacks an amino-acid binding pocket and so does not read N-terminal degrons.

    Evidence X-ray crystallography of the UBR-box (domain-swapped dimer)

    PMID:28691247

    Open questions at the time
    • Functional consequence inferred without mutagenesis
    • Dimer assignment later contradicted
  11. 2021 High

    Expanded FBXO11 substrate biology to chromatin and hematopoiesis, identifying BAHD1 as a target whose degradation permits erythroid maturation, and quantifying FBXO11 mutation/haploinsufficiency in Burkitt lymphoma cooperating with MYC.

    Evidence Knockout erythroblasts, ChIP-seq, ubiquitylation assays, BAHD1/PRC2 depletion rescue; patient sequencing, BCL6 degradation assays, conditional KO/MYC lymphoma model

    PMID:33156908 PMID:34625792

    Open questions at the time
    • Recognition determinants on BAHD1 not mapped
    • How a single ligase coordinates lineage-specific substrate choice unclear
  12. 2022 High

    Linked FBXO11 to adaptive immunity by establishing CIITA as a degradation substrate, so FBXO11 loss elevates MHC class II expression.

    Evidence Unbiased Co-IP/MS, cycloheximide chase, ubiquitylation assays, FBXO11 KO cells, MHC-II flow cytometry (two independent papers)

    PMID:36179686 PMID:37279268

    Open questions at the time
    • CIITA degron not defined
    • Interplay with FBXO11's tumor-suppressor and antigen-presentation roles not integrated
  13. 2023 Medium

    Extended FBXO11 into innate immunity, metabolism, and inflammation, showing K63-ubiquitylation of TRAF3 to amplify type I IFN, degradation of hnRNPA2B1 (antagonized by CAND1), and BCL6/BAHD1-dependent control of macrophage responses to bacterial toxins.

    Evidence Co-IP, K63-ubiquitination assays, IFN reporters, MLN4921 inhibition; MS, GST pull-down, in vivo tumor models; genome-wide CRISPR screen, genetic KO, C5aR1 and IL-1β assays

    PMID:36977592 PMID:37837399

    Open questions at the time
    • NEDD8-dependence of TRAF3 K63 ubiquitylation mechanistically thin
    • Mechanism of C5aR1 mRNA regulation unresolved
    • Single labs for each axis
  14. 2024 Medium

    Broadened the EMT/migration program and tissue contexts, adding ZEB1, β-catenin (via NDR1 phosphorylation), KIF2C, Fosl2, and Snail1 in bone as degradation substrates, and showing regulatory inputs from ERK3, ZNF217, and EBNA3C.

    Evidence Co-IP, K48-linked ubiquitylation assays, epistasis rescue, xenograft/metastasis and conditional KO mouse models, competitive binding assays, ChIP for transcriptional repressors

    PMID:36863499 PMID:38201533 PMID:38864622 PMID:39309441 PMID:39409891 PMID:39581215 PMID:40447129

    Open questions at the time
    • Most axes from single labs
    • Substrate-recognition motifs largely unmapped
    • Relative physiological hierarchy of the many substrates unknown
  15. 2025 Medium

    Revealed a non-degradative mitochondrial role: FBXO11 K63-ubiquitylates cytosolic LONP1 to promote its mitochondrial import and Complex IV assembly, with loss imparting myeloid-biased stem cell properties and cooperating in AML; a re-determined UBR-box structure corrected the prior dimer to a monomer.

    Evidence Co-IP, K63-ubiquitination assays, mitochondrial fractionation, Complex IV assembly assays, HSPC culture and xenograft; 1.5 Å crystallography and N-degron binding assay; iPSC-neuron and Drosophila models with proteasome-activator rescue

    PMID:40099808 PMID:40114442 PMID:41289019

    Open questions at the time
    • How K63 ubiquitylation drives LONP1 import mechanistically unclear
    • Conflicting UBR-box structural models
    • Neuronal substrate(s) not identified
  16. 2026 Medium

    Connected FBXO11 to RNA processing and myeloid malignancy, showing SCF-FBXO11 ubiquitylates NPM1 to restrain alternative splicing, with disease mutations clustering in a disordered NPM1-binding N-terminus and MYC/TLR2 controlling FBXO11 expression in MDS.

    Evidence Multi-omics proteomics/transcriptomics, Co-IP, ubiquitylation assays, Fbxo11 KO mouse MDS models, ChIP for MYC at the FBXO11 promoter

    PMID:41542766

    Open questions at the time
    • Whether NPM1 ubiquitylation is degradative or regulatory not fully resolved
    • Single lab, not independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single F-box protein achieves selective recognition of such a broad substrate set, and how its degradative versus non-degradative (neddylation, K63-ubiquitylation, methyltransferase) activities are partitioned, remains unresolved.
  • No unifying degron/recognition code mapped across substrates
  • Physiological relevance of the PRMT9 methyltransferase activity unestablished
  • Structural model of the substrate-binding region disputed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016874 ligase activity 4 GO:0060090 molecular adaptor activity 3 GO:0016740 transferase activity 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 2
Partners
BAHD1BCL6CDT2CIITALONP1NPM1SNAI1ZEB1
Complex memberships
SCF (SKP1-CUL1-FBXO11) E3 ubiquitin ligase

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 FBXO11 is the substrate-recognition subunit of an SCF (SKP1-CUL1-F-box) ubiquitin ligase complex that directly ubiquitylates BCL6, targeting it for proteasomal degradation. Tumor-derived FBXO11 mutants displayed impaired ability to induce BCL6 degradation, and reconstitution of FBXO11 in FBXO11-deleted DLBCL cells promoted BCL6 ubiquitylation and degradation, inhibited proliferation, and induced cell death. Co-immunoprecipitation, ubiquitylation assays, reconstitution in FBXO11-deleted cell lines, mutagenesis of tumor-derived alleles, xenograft tumor suppression assay Nature High 22113614
2014 SCF-FBXO11 ubiquitylates SNAIL and targets it for proteasomal degradation, but only after SNAIL Ser-11 is phosphorylated by protein kinase D1 (PKD1). This PKD1-FBXO11-SNAIL axis suppresses EMT, tumor initiation, and metastasis in breast cancer models. Genome-wide E3 ligase siRNA library screen, co-immunoprecipitation, ubiquitylation assays, phospho-mutant analysis, breast cancer xenograft and metastasis models Cancer cell High 25203322
2006 FBXO11 is a component of the SCF complex and acts as an adaptor protein that promotes neddylation (NEDD8 conjugation) of p53, including at Lys-320 and Lys-321, inhibiting p53 transcriptional activity. This was demonstrated both in vitro and in vivo. In vitro neddylation assay, co-immunoprecipitation, p53 transcriptional reporter assays, site-directed mutagenesis of p53 lysine residues The Journal of biological chemistry High 17098746
2006 FBXO11 (designated PRMT9) harbors a protein arginine methyltransferase domain and immunopurified protein exhibits methyltransferase activity, forming monomethylarginine, symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) on arginine residues. Immunopurification of recombinant protein expressed in HeLa cells and E. coli, in vitro methyltransferase activity assay, mass spectrometry identification of methylation products Biochemical and biophysical research communications Medium 16487488
2013 FBXO11 interacts with CDT2 (a DCAF substrate receptor of CRL4) and recruits CDT2 to the SCF-FBXO11 complex to promote its proteasomal degradation. Unlike typical SCF substrates, CDK-mediated phosphorylation of Thr464 in the CDT2 degron inhibits (rather than promotes) recognition by FBXO11. This regulation of CDT2 is evolutionarily conserved from C. elegans to humans and controls the timing of cell-cycle exit. Affinity purification and mass spectrometry, co-immunoprecipitation, ubiquitylation assays, phosphorylation mutant analysis, C. elegans genetic studies Molecular cell High 23478441
2013 CRL1-FBXO11 polyubiquitylates CDT2 and promotes its degradation, independent of CRL4A-mediated autoubiquitylation of CDT2. FBXO11-mediated CDT2 degradation stabilizes p21 and Set8/Pr-Set7, which is important for the response to TGF-β (enabling Set8-dependent shutoff of Smad2 activation) and for stimulating epithelial cell migration. Co-immunoprecipitation, ubiquitylation assays, cycloheximide chase, siRNA knockdown, TGF-β signaling assays, migration assays Molecular cell High 23478445
2014 The C. elegans ortholog DRE-1/FBXO11 functions in an SCF E3 ubiquitin ligase complex to directly target the conserved transcription factor BLMP-1/BLIMP-1 for proteasomal degradation, governing developmental timing and other life history traits. Direct protein interaction and degradation function for worm and human FBXO11 with BLMP-1/BLIMP-1 was demonstrated. Genetic epistasis (suppressor analysis), co-immunoprecipitation, protein stability assays, C. elegans developmental timing assays Developmental cell High 24613396
2016 FBXO11 loss in germinal center (GC)-specific knockout mice leads to increased GC B cells, altered dark zone/light zone ratio, elevated BCL6 protein, and reduced BCR-mediated BCL6 degradation, establishing that FBXO11 physiologically controls BCL6 levels during the GC reaction and that its inactivation leads to lymphoproliferative disease. GC-specific conditional FBXO11 knockout mice, flow cytometry, immunofluorescence, BCL6 protein stability assays Blood High 27166359
2015 FBXO11 promotes ubiquitin-mediated degradation of multiple Snail family members (SNAI1, SNAI2/Slug, Scratch), independent of SNAI1 phosphorylation in vitro. Depletion of FBXO11 in epithelial cancer cells causes Snail accumulation, EMT, and invasion. In FBXO11-knockout mice, neonatal lethality, epidermal thickening, and increased Snail protein in epidermis confirm FBXO11 as a physiological ubiquitin ligase of Snail. C. elegans fbxo11 mutant phenotype is suppressed by inactivation of Snail homologs. Co-immunoprecipitation, ubiquitylation assays, FBXO11 knockout mice, C. elegans genetic epistasis, cell invasion assays Cancer letters High 25827072
2021 FBXO11 promotes ubiquitin-mediated proteasomal degradation of BAHD1, an H3K27me3 reader that recruits transcriptional corepressors and physically interacts with PRC2. In FBXO11-deficient erythroblasts, BAHD1 accumulates at bivalent gene promoters, prevents GATA1 binding, and blocks erythroid maturation genes. Depletion of either BAHD1 or PRC2 restores gene expression in FBXO11-/- erythroblasts. FBXO11 knockout mouse erythroblasts, co-immunoprecipitation, ChIP-seq, ubiquitylation assays, rescue experiments by BAHD1/PRC2 depletion, gene expression analysis Blood High 33156908
2022 FBXO11 mediates ubiquitin-dependent proteasomal degradation of CIITA (the master transcriptional regulator of MHC class II), thereby suppressing MHC class II surface expression. FBXO11 was identified as a CIITA-binding partner by unbiased proteomics, and cycloheximide chase assays showed FBXO11 mainly controls CIITA half-life. FBXO11-deficient cells show increased MHC-II and related gene expression. Unbiased proteomic screen (co-IP/MS), cycloheximide chase, ubiquitylation assays, FBXO11 knockout cells, MHC-II surface expression (flow cytometry), promoter/transcriptional reporter assays Cancer cell High 36179686 37279268
2023 FBXO11 directly binds hnRNPA2B1 and promotes its ubiquitylation and proteasomal degradation via the SCF-FBXO11 complex. This axis is disrupted by CAND1, which dissociates the SCF complex, leading to hnRNPA2B1 accumulation and lipid metabolic reprogramming in hepatocellular carcinoma. Mass spectrometry, co-immunoprecipitation, GST pull-down, ubiquitylation assays, AAV-shCAND1 in vivo tumor models Clinical and translational medicine Medium 37837399
2015 FBXO11 represses HIF-1α expression by destabilizing HIF-1α mRNA (not by direct ubiquitylation of HIF-1α protein). A FBXO11 mutant lacking the F-box domain failed to rescue HIF-1α expression upon FBXO11 knockdown, implicating the E3 ligase activity of FBXO11 in ubiquitinating proteins that control HIF-1α mRNA stability. siRNA knockdown, HIF-1α reporter assays, mRNA stability assay, F-box deletion mutant Biochemical and biophysical research communications Medium 26187670
2017 Crystal structure of the UBR-box domain from human UBR6/FBXO11 reveals a unique zinc-mediated domain-swapped dimer (three protein chains reconstituting the monomeric UBR-box fold). Structural analysis indicates that UBR6/FBXO11 lacks an amino acid binding pocket, explaining why it does not bind N-terminal degradation signals unlike other UBR family members. X-ray crystallography Protein science Medium 28691247
2025 A new crystal structure of the UBR-box from human UBR6/FBXO11 at 1.5 Å resolution shows a monomer with a classical UBR fold, contradicting the previously reported domain-swapped dimer. N-degron binding assays confirmed no binding of basic type-1 N-degrons by UBR6/FBXO11. X-ray crystallography (1.5 Å), N-degron binding assay Protein science Medium 40099808
2009 In the Jeff mouse model carrying a mutation in Fbxo11, phospho-Smad2 (pSmad2) is significantly upregulated and shows increased nuclear localization in epithelia. Mice heterozygous for both Jeff and Smad2 mutations recapitulate many Jeff homozygous phenotypes. No direct physical interaction between Fbxo11 and Smad2 was detected by tissue immunoprecipitation. Fbxo11 mutation reduces p53 levels, suggesting Fbxo11 stabilizes p53 which in turn limits pSmad2 nuclear accumulation. Immunohistochemistry, tissue immunoprecipitation (negative for direct interaction), genetic epistasis (Jeff/Smad2 double heterozygotes), p53 protein level analysis PathoGenetics Medium 19580641
2015 In mouse embryonic lung, FBXO11 and p53 physically interact, and the Jeff mutation in Fbxo11 prevents this interaction. p53 homozygous mutants and Jeff/p53 double heterozygotes show similar epithelial developmental defects and raised pSMAD2 levels as Fbxo11 homozygotes, establishing genetic epistasis between FBXO11 and p53 in regulating TGF-β pathway output. Co-immunoprecipitation from embryonic lung tissue, genetic epistasis (p53 KO and Jeff/p53 double heterozygote mice), immunofluorescence for pSMAD2 Disease models & mechanisms Medium 26471094
2021 FBXO11 mutations are found in 23% of Burkitt lymphoma patients and impair BCL6 degradation. Conditional deletion of one or two FBXO11 copies in mice cooperated with oncogenic MYC to accelerate B-cell lymphoma onset, establishing FBXO11 as a haploinsufficient tumor suppressor in B-cell lymphoma. Sequencing of patient samples, BCL6 degradation assays in human BL cell lines, conditional FBXO11 knockout mouse B-cell lymphoma model Blood advances High 34625792
2023 FBXO11 facilitates the assembly of the TRAF3-TBK1-IRF3 complex by mediating K63-linked ubiquitination of TRAF3 in a NEDD8-dependent manner, thereby promoting TBK1 and IRF3 phosphorylation and amplifying type I interferon signaling. The NEDD8-activating enzyme inhibitor MLN4921 blocked this FBXO11-TRAF3-IFN-I axis. Co-immunoprecipitation, K63 ubiquitination assay, phosphorylation assays (TBK1, IRF3), MLN4921 pharmacological inhibition, FBXO11 overexpression/knockdown with IFN reporter assays Journal of medical virology Medium 36977592
2024 NDR1 phosphorylates β-catenin at Ser33/Ser37, facilitating its interaction with FBXO11. FBXO11 then mediates ubiquitylation and cytoplasmic degradation of β-catenin. Additionally, the NDR1-FBXO11 complex induces JNK2 ubiquitination, impeding β-catenin nuclear translocation. This dual mechanism suppresses EMT and prostate cancer metastasis. Immunoprecipitation, Western blotting, immunofluorescence, ubiquitylation assays, protein stability assays, nude mouse lung metastasis model International journal of biological sciences Medium 39309441
2023 FBXO11 mediates ubiquitin-dependent proteasomal degradation of BAHD1 and also promotes BCL6 ubiquitylation and degradation in macrophages. FBXO11 regulates C5aR1 expression at the mRNA level and dampens IL-1β secretion after NLRP3 activation through BCL6-dependent and BCL6-independent mechanisms in response to bacterial PVL toxin. Genome-wide CRISPR/Cas9 screen, FBXO11 genetic deletion, C5aR1 expression assays, IL-1β ELISA, ectopic C5aR1 rescue experiments Life science alliance Medium 36977592
2023 FBXO11 governs macrophage cell death and inflammation in response to Panton-Valentine leukocidin (PVL). Genetic deletion of FBXO11 reduced C5aR1 expression at the mRNA level, and ectopic C5aR1 expression or LPS priming in FBXO11-/- macrophages restored PVL toxicity. FBXO11 also dampens IL-1β secretion after NLRP3 activation via BCL6-dependent and BCL6-independent mechanisms. Genome-wide CRISPR/Cas9 screen, FBXO11 genetic deletion, C5aR1 rescue experiments, NLRP3 activation assays, IL-1β measurement Life science alliance Medium 36977592
2023 FBXO11 deficiency in osteoblasts leads to Snail1 protein accumulation (reduced Snail1 ubiquitylation), suppression of osteogenic activity, and inhibition of bone matrix mineralization. Osteoblast-specific conditional FBXO11 knockout mice showed reduced bone growth and osteogenic activity without changes in osteoclast activity. Lentiviral FBXO11 knockdown and overexpression in MC3T3-E1 cells, osteoblast-specific conditional KO mouse models (Col1a1-ERT2 and Bglap2 promoters), ubiquitylation assay, osteogenic differentiation assays Bone Medium 36863499
2024 ERK3 interacts with Snail and enhances Snail protein stability by inhibiting the binding of FBXO11 to Snail, thereby preventing FBXO11-mediated Snail ubiquitylation and degradation. ERK3 could not directly phosphorylate Snail but acted by blocking FBXO11-Snail interaction. Co-immunoprecipitation, ubiquitylation assays, protein stability assays, competitive binding assays, pancreatic cancer clinical sample analysis Cancers Medium 38201533
2024 FBXO11 recognizes and promotes ubiquitin-mediated proteasomal degradation of ZEB1, a core inducer of EMT. Depletion of FBXO11 in lung cancer cells causes ZEB1 accumulation and increased invasion, while FBXO11 overexpression reduces ZEB1 and invasiveness. ZEB1 depletion suppresses the increased migration/invasion caused by FBXO11 knockdown. Co-immunoprecipitation, ubiquitylation assays, FBXO11 knockdown/overexpression, rescue by ZEB1 depletion, xenograft tumor assays Cancers Medium 39409891
2024 FBXO11 directly interacts with EBNA3C (an EBV latent antigen) through EBNA3C residues 50-100, and the presence of both EBNA3C and FBXO11 significantly enhances BCL6 ubiquitylation and degradation via the SCF-FBXO11 complex. FBXO11 knockdown suppresses EBV-driven lymphoblastoid cell line transformation. Co-immunoprecipitation, ubiquitylation assays, FBXO11 knockdown, LCL transformation assay Journal of virology Medium 38864622
2025 FBXO11 interacts with and catalyzes K63-linked ubiquitylation of LONP1 in the cytosol, promoting LONP1 entry into mitochondria. FBXO11 or LONP1 depletion reduces mitochondrial respiration through impaired LONP1 chaperone activity to assemble electron transport chain Complex IV, imparting myeloid-biased stem cell properties in HSPCs. In a xenograft model, FBXO11 depletion cooperated with AML1-ETO and KRAS-G12D to generate transplantable AML. Co-immunoprecipitation, K63 ubiquitination assay, mitochondrial fractionation, electron transport chain complex IV assembly assay, CD34+ HSPC culture, xenograft transplantation model The Journal of clinical investigation High 41289019
2026 SCF-FBXO11 facilitates ubiquitylation of NPM1, and FBXO11 deletion results in reorganization of NPM1 and de-repression of alternative splicing. FBXO11 and NPM1 form a network regulating spliceosome and ribosome components. Rare FBXO11 mutations map to an intrinsically disordered N-terminal region responsible for NPM1 binding. MYC was found to occupy the FBXO11 promoter and its eviction by TLR2 activation explains reduced FBXO11 expression in MDS. Multi-omics (proteomics, transcriptomics), label-free quantitative proteomics, co-immunoprecipitation, ubiquitylation assays, Fbxo11 knockout mouse MDS models, ChIP assay for MYC at FBXO11 promoter The Journal of clinical investigation Medium 41542766
2024 FBXO11 promotes K48-linked ubiquitylation and proteasomal degradation of KIF2C. Conditional FBXO11 expression suppresses ovarian cancer cell proliferation, migration, invasion, and xenograft tumor growth; KIF2C knockdown reverses tumor-promoting effects of FBXO11 downregulation. ZNF217 transcriptionally represses FBXO11 expression. Tet-on inducible FBXO11 expression, ubiquitylation assay (K48-linkage specific), KIF2C knockdown rescue, xenograft and peritoneal metastasis models, ChIP for ZNF217 at FBXO11 promoter Cellular signalling Medium 40447129
2024 FBXO11 mediates ubiquitin-dependent proteasomal degradation of Fosl2. FBXO11 overexpression in podocytes reduced Fosl2 protein via ubiquitin-dependent degradation, maintained mitochondrial function, and prevented podocyte apoptosis in adriamycin-induced nephropathy. Fosl2 overexpression abolished protective effects of FBXO11, and the mitochondrial fission inhibitor mdivi-1 reversed effects of the FBXO11/Fosl2 axis. Lentiviral FBXO11 overexpression, ubiquitylation assays, Fosl2 rescue experiments, mitochondrial function assays, mdivi-1 pharmacological inhibition, in vivo mouse ADR nephropathy model Experimental cell research Medium 39581215
2006 A mutation in Fbxo11 underlies the Jeff mouse mutant that develops chronic suppurative otitis media. Fbxo11 is expressed in epithelial cells of the middle ear from late embryonic stages through postnatal day 13. Homozygous Jeff mutants and a hypomorphic Mutt allele show cleft palate and facial clefting, establishing FBXO11 as important in epithelial development of the middle ear and palate. Positional cloning, mutant mouse characterization, immunohistochemistry/in situ hybridization for tissue expression Human molecular genetics Medium 17035249
2010 In melanocytes, FBXO11 knockdown causes ER swelling and retention of tyrosinase co-localized with calreticulin in the ER, preventing its export. Tyrosinase protein levels were markedly elevated following FBXO11 siRNA, suggesting FBXO11 is required for proper ER function and tyrosinase export from the ER in melanocytes. siRNA knockdown, electron microscopy (ER morphology), confocal co-localization of tyrosinase and calreticulin, Western blot International journal of molecular medicine Low 20514423
2025 Loss of FBXO11 in human iPSC-derived neurons causes disrupted transcriptional networks related to neuronal differentiation, migration, and cell signaling, impaired neuronal migration, and abnormal proliferation/differentiation balance. In Drosophila, fbxo11 knockdown impairs dendritic development and behavior. Proteasome-activating substances (including verapamil) alleviated these FBXO11-deficiency phenotypes in both human neurons and flies. CRISPR-Cas9 FBXO11-deficient human iPSC-derived neurons, Drosophila tissue-specific knockdown, RNA sequencing, neuronal migration assay, pharmacological proteasome activation HGG advances Medium 40114442

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature 242 22113614
2014 PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis. Cancer cell 199 25203322
2006 FBXO11 promotes the Neddylation of p53 and inhibits its transcriptional activity. The Journal of biological chemistry 169 17098746
2006 FBXO11/PRMT9, a new protein arginine methyltransferase, symmetrically dimethylates arginine residues. Biochemical and biophysical research communications 123 16487488
2015 MiRNA-621 sensitizes breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity. Oncogene 98 25867061
2015 The oncogenic microRNA-21 inhibits the tumor suppressive activity of FBXO11 to promote tumorigenesis. The Journal of biological chemistry 95 25589783
2015 FBXO11 promotes ubiquitination of the Snail family of transcription factors in cancer progression and epidermal development. Cancer letters 78 25827072
2006 A mutation in the F-box gene, Fbxo11, causes otitis media in the Jeff mouse. Human molecular genetics 77 17035249
2013 Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the SCF(Fbxo11) ubiquitin ligase. Molecular cell 70 23478441
2013 CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration. Molecular cell 69 23478445
2014 DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation. Developmental cell 65 24613396
2006 Association of the FBXO11 gene with chronic otitis media with effusion and recurrent otitis media: the Minnesota COME/ROM Family Study. Archives of otolaryngology--head & neck surgery 52 16847180
2011 FBXO11, a regulator of the TGFβ pathway, is associated with severe otitis media in Western Australian children. Genes and immunity 50 21293382
2016 FBXO11 inactivation leads to abnormal germinal-center formation and lymphoproliferative disease. Blood 47 27166359
2022 Inhibition of the CtBP complex and FBXO11 enhances MHC class II expression and anti-cancer immune responses. Cancer cell 44 36179686
2018 De Novo Variants in the F-Box Protein FBXO11 in 20 Individuals with a Variable Neurodevelopmental Disorder. American journal of human genetics 44 30057029
2009 Regulation of TGF-beta signalling by Fbxo11, the gene mutated in the Jeff otitis media mouse mutant. PathoGenetics 41 19580641
2018 The tumor suppressive miR-26a regulation of FBXO11 inhibits proliferation, migration and invasion of hepatocellular carcinoma cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 37 29518611
2021 FBXO11-mediated proteolysis of BAHD1 relieves PRC2-dependent transcriptional repression in erythropoiesis. Blood 31 33156908
2019 De novo variants in FBXO11 cause a syndromic form of intellectual disability with behavioral problems and dysmorphisms. European journal of human genetics : EJHG 31 30679813
2020 Long non-coding RNA NNT-AS1 regulates proliferation, apoptosis, inflammation and airway remodeling of chronic obstructive pulmonary disease via targeting miR-582-5p/FBXO11 axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 32768929
2018 De novo FBXO11 mutations are associated with intellectual disability and behavioural anomalies. Human genetics 29 29796876
2023 FBXO11 constitutes a major negative regulator of MHC class II through ubiquitin-dependent proteasomal degradation of CIITA. Proceedings of the National Academy of Sciences of the United States of America 23 37279268
2023 Cullin-associated and neddylation-dissociated 1 regulate reprogramming of lipid metabolism through SKP1-Cullin-1-F-boxFBXO11 -mediated heterogeneous nuclear ribonucleoprotein A2/B1 ubiquitination and promote hepatocellular carcinoma. Clinical and translational medicine 23 37837399
2020 FBXO11 is a candidate tumor suppressor in the leukemic transformation of myelodysplastic syndrome. Blood cancer journal 22 33024076
2021 Circ-RBMS1 Knockdown Alleviates CSE-Induced Apoptosis, Inflammation and Oxidative Stress via Up-Regulating FBXO11 Through miR-197-3p in 16HBE Cells. International journal of chronic obstructive pulmonary disease 20 34295155
2020 LINC01436, regulating miR-585 and FBXO11, is an oncogenic lncRNA in the progression of gastric cancer. Cell biology international 20 31829474
2015 FBXO11 represses cellular response to hypoxia by destabilizing hypoxia-inducible factor-1α mRNA. Biochemical and biophysical research communications 20 26187670
2019 miR-324-5p upregulation potentiates resistance to cisplatin by targeting FBXO11 signalling in non-small cell lung cancer cells. Journal of biochemistry 19 31778188
2024 NDR1/FBXO11 promotes phosphorylation-mediated ubiquitination of β-catenin to suppress metastasis in prostate cancer. International journal of biological sciences 18 39309441
2018 Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activity. Molecular cancer 18 30526604
2013 Regulation of TGF-β signaling, exit from the cell cycle, and cellular migration through cullin cross-regulation: SCF-FBXO11 turns off CRL4-Cdt2. Cell cycle (Georgetown, Tex.) 18 23892434
2010 The role of VIT1/FBXO11 in the regulation of apoptosis and tyrosinase export from endoplasmic reticulum in cultured melanocytes. International journal of molecular medicine 17 20514423
2015 Interactions between the otitis media gene, Fbxo11, and p53 in the mouse embryonic lung. Disease models & mechanisms 16 26471094
2017 A mouse-to-man candidate gene study identifies association of chronic otitis media with the loci TGIF1 and FBXO11. Scientific reports 15 28970529
2019 Chronic otitis media is initiated by a bulla cavitation defect in the FBXO11 mouse model. Disease models & mechanisms 13 30898767
2019 miR-376a inhibits the proliferation and invasion of osteosarcoma by targeting FBXO11. Human cell 13 31079326
2017 Crystal structure of the UBR-box from UBR6/FBXO11 reveals domain swapping mediated by zinc binding. Protein science : a publication of the Protein Society 13 28691247
2009 VIT1/FBXO11 knockdown induces morphological alterations and apoptosis in B10BR mouse melanocytes. International journal of molecular medicine 12 19360327
2021 Frequent mutations of FBXO11 highlight BCL6 as a therapeutic target in Burkitt lymphoma. Blood advances 11 34625792
2023 FBXO11 regulates bone development. Bone 10 36863499
2023 ERK3 Increases Snail Protein Stability by Inhibiting FBXO11-Mediated Snail Ubiquitination. Cancers 9 38201533
2020 The F-box protein FBXO11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin-mediated degradation of Snail. FEBS open bio 9 32657545
2024 Tanshinone IIA alleviates IL-1β-induced chondrocyte apoptosis and inflammation by regulating FBXO11 expression. Clinics (Sao Paulo, Brazil) 7 38677194
2020 Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media. Frontiers in genetics 7 32117459
2021 Constitutional 2p16.3 deletion including MSH6 and FBXO11 in a boy with developmental delay and diffuse large B-cell lymphoma. Familial cancer 6 33811277
2024 FBXO11 Mediates Ubiquitination of ZEB1 and Modulates Epithelial-to-Mesenchymal Transition in Lung Cancer Cells. Cancers 5 39409891
2022 Ultrasound-targeted microbubble destruction-mediated silencing of FBXO11 suppresses development of pancreatic cancer. Human cell 5 35437704
2023 FBXO11 governs macrophage cell death and inflammation in response to bacterial toxins. Life science alliance 4 36977592
2022 New ocular findings in a patient with a novel pathogenic variant in the FBXO11 gene. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus 3 35940561
2025 MiR-21-5p enhances differentiation and mitigates oleic acid-induced lipid droplet accumulation in C2C12 myoblasts by targeting FBXO11. Animal bioscience 2 40045615
2025 Regulatory polymorphisms of MSH6, MSH2, FBXO11, and PPP1R21 genes affect survival of patients with immunotherapy-treated lung cancer. Journal for immunotherapy of cancer 2 40889797
2024 FBXO11 variants are associated with intellectual disability and variable clinical manifestation in Chinese affected individuals. Journal of human genetics 2 38740982
2024 The F-box E3 ligase protein FBXO11 regulates EBNA3C-associated degradation of BCL6. Journal of virology 2 38864622
2023 FBXO11 amplifies type I interferon signaling to exert antiviral effects by facilitating the assemble of TRAF3-TBK1-IRF3 complex. Journal of medical virology 2 36897010
2025 The miR-155-5p/FBXO11 axis inhibits the progression of gastric cancer via the mTOR pathway. Translational cancer research 1 40104748
2024 Fbxo11 maintains mitochondrial function and prevents podocyte injury in adriamycin-induced nephropathy by mediating the ubiquitin degradation of Fosl2. Experimental cell research 1 39581215
2021 [Corrigendum] The role of VIT1/FBXO11 in the regulation of apoptosis and tyrosinase export from endoplasmic reticulum in cultured melanocytes. International journal of molecular medicine 1 34878147
2010 [Expression of InnVit/FBXO11 in vitiligo and its role in tyrosinase export from endoplasmic reticulum]. Zhonghua yi xue za zhi 1 20646433
2026 FBXO11 suppression rewires an NPM1-centered interactome influencing the progression of myelodysplastic syndrome. The Journal of clinical investigation 0 41542766
2026 RBM15-Mediated m6A Modification Regulates Proliferation and Migration of Pancreatic Cancer Cells via the lncRNA LINC01320/miR-1287-5p/FBXO11 Axis. Biomolecules & therapeutics 0 42059032
2025 Revisiting the structure of UBR box from human UBR6. Protein science : a publication of the Protein Society 0 40099808
2025 Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency. HGG advances 0 40114442
2025 Tumor suppressor FBXO11 drives ubiquitin proteasomal degradation of KIF2C to limit ovarian cancer progression and is transcriptionally repressed by ZNF217. Cellular signalling 0 40447129
2025 [Clinical and genetic analysis of a child with Intellectual developmental disorder with dysmorphic features and behavioral abnormalities due to a de novo variant of FBXO11 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 41230589
2025 Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1. The Journal of clinical investigation 0 41289019
2024 How many phenotypes for the FBXO11 related disease? Report on a new patient with a tricho-rhino-phalangeal like phenotype. European journal of medical genetics 0 38679370
2023 Retraction statement: Shao, L., Zhang, X. and Yao, Q. (2020), The F-box protein FBXO11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin-mediated degradation of Snail. FEBS Open Bio, 10: 1810-1820. FEBS open bio 0 37219054
2023 Partial Response to Crizotinib in a Lung Adenocarcinoma Patient with a Novel FBXO11 (Intergenic)-ALK (Exon 20-29) Fusion. OncoTargets and therapy 0 37441362

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