Affinage

CBLB

E3 ubiquitin-protein ligase CBL-B · UniProt Q13191

Length
982 aa
Mass
109.5 kDa
Annotated
2026-04-28
100 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CBLB encodes a RING-type E3 ubiquitin ligase that functions as a central negative regulator of immune cell activation thresholds across T cells, NK cells, and myeloid lineages, while also controlling receptor tyrosine kinase signaling, bone remodeling, and skeletal muscle homeostasis. Its catalytic RING finger domain ubiquitinates a broad substrate repertoire—including PI3K p85, Vav1, PLCγ-1, CARMA1, NFATc1, TAM receptors, SYK, dectin-1/2, IRS-1, GluN2B, Foxp3, EGFR, TrkA, and STAT5—to enforce peripheral T-cell tolerance and anergy, suppress NF-κB and calcium signaling, limit innate antifungal responses, and attenuate growth factor receptor signaling through ubiquitin-dependent degradation or non-degradative signaling modulation (PMID:10646608, PMID:11526404, PMID:15308098, PMID:21248250, PMID:27428901, PMID:19546233, PMID:24553136, PMID:32606037). Cbl-b activity is itself regulated by CD28-induced auto-ubiquitination and degradation, TAM receptor-mediated phosphorylation at Y133 and Y363, complex formation with the pH-sensitive phosphatase STS1 that tunes T-cell function in acidic tumor microenvironments, and intramolecular conformational control exploited by small-molecule inhibitors that lock the TKBD–LHR interface (PMID:12193687, PMID:31531847, PMID:38091950, PMID:38104184). Loss of Cbl-b or its E3 ligase activity unleashes CD8+ T-cell and NK-cell anti-tumor immunity, enabling rejection of established tumors and metastases, and reverses T-cell exhaustion in tumor-infiltrating and CAR T-cell settings (PMID:17364027, PMID:24553136, PMID:33462140).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 Medium

    Initial biochemical work established that Cbl-b is phosphorylated upon growth factor (EGF, FLT3L, IL-7) stimulation and associates with key signaling adaptors (Grb2, SHC, PI3K p85), positioning it as a signaling hub downstream of receptor tyrosine kinases before its E3 ligase function was appreciated.

    Evidence Co-immunoprecipitation and phosphorylation assays in hematopoietic and EGFR-expressing cell lines

    PMID:10086340 PMID:9614102

    Open questions at the time
    • E3 ligase activity not yet tested
    • overexpression system without loss-of-function validation
    • physiological relevance in primary cells unknown
  2. 2000 High

    Two independent knockout studies revealed that Cbl-b sets the CD28 co-stimulation requirement for T-cell activation by suppressing Vav1 phosphorylation, establishing Cbl-b as the critical gatekeeper of peripheral T-cell activation thresholds.

    Evidence Gene-targeted Cbl-b KO mice; genetic epistasis with CD28-/- mice; Vav activation and T-cell proliferation/cytokine assays

    PMID:10646608 PMID:10646609

    Open questions at the time
    • Direct enzymatic mechanism on Vav not defined
    • whether Cbl-b ubiquitinates Vav directly or acts indirectly remained unknown
  3. 2001 High

    Identification of PI3K p85 as a direct Cbl-b ubiquitination substrate revealed a RING-finger-dependent, proteolysis-independent mechanism whereby Cbl-b controls PI3K recruitment to CD28 and TCRζ, explaining how Cbl-b restrains PI3K/Akt signaling in T cells.

    Evidence In vitro ubiquitination assay with RING finger mutagenesis; PI3K inhibitor rescue of Cbl-b-/- T-cell hyperactivation; co-IP with CD28/TCRζ

    PMID:11087752 PMID:11526404

    Open questions at the time
    • Non-degradative ubiquitin signal on p85 not fully characterized (chain type unknown)
    • whether this is the sole PI3K-regulatory mechanism of Cbl-b was unclear
  4. 2001 High

    Demonstration that Cbl-b coordinates EGFR signaling complex degradation through its TKB and RING domains, and that it is itself degraded upon EGFR activation, established Cbl-b as a self-limiting negative regulator of receptor tyrosine kinase signaling beyond the immune system.

    Evidence EGF stimulation with RING/TKB mutagenesis; lysosomal and proteasomal inhibitors; Western blot for EGFR/Grb2/Shc complex degradation

    PMID:11375397

    Open questions at the time
    • Relative contributions of Cbl-b vs. c-Cbl to EGFR degradation not resolved
    • in vivo relevance in epithelial tissues not tested
  5. 2002 High

    CD28 co-stimulation was shown to selectively induce Cbl-b ubiquitination and degradation, establishing a feedforward mechanism: CD28 removes Cbl-b to lower the activation threshold, while CIN85 binding to Cbl-b was found necessary for receptor internalization but dispensable for polyubiquitination.

    Evidence Ubiquitination assay comparing CD3 vs. CD28 stimulation in WT and CD28-/- T cells; CIN85 dominant-negative and EGFR internalization assay

    PMID:12177062 PMID:12193687

    Open questions at the time
    • Identity of the E3 ligase ubiquitinating Cbl-b itself not determined
    • CIN85-Cbl-b function in T cells (vs. EGFR context) not tested
  6. 2002 High

    Discovery that Cbl-b positively regulates BCR-mediated calcium signaling by scaffolding PLC-γ2/Btk/BLNK complexes revealed a context-dependent positive signaling role, contrasting with its inhibitory function in T cells.

    Evidence Cbl-b-deficient DT40 B cells; gain-of-function in WEHI-231; Ca2+ mobilization; co-IP of PLCγ2/Btk/BLNK; domain deletion mutagenesis

    PMID:12093870

    Open questions at the time
    • Whether this positive role depends on E3 ligase activity or adaptor function was not resolved
    • relevance to primary mammalian B cells not confirmed
  7. 2004 High

    Cbl-b was established as essential for T-cell anergy induction and identified as a mediator of regulatory T-cell suppression: tolerizing signals upregulate Cbl-b to suppress PLCγ-1 phosphorylation and calcium mobilization, while Cbl-b-/- T cells escape Treg- and TGF-β-mediated suppression.

    Evidence In vitro/in vivo tolerance assays in Cbl-b KO mice; PLCγ-1 phosphorylation and Ca2+ flux; Treg suppression and TGF-β assays with Smad3 analysis

    PMID:15240694 PMID:15308098

    Open questions at the time
    • Direct substrate linking Cbl-b to TGF-β resistance not identified
    • mechanism downstream of Smad3 not resolved
  8. 2006 High

    Cbl-b was shown to ubiquitinate IRS-1 for degradation in osteoblasts after denervation and later in skeletal muscle upon unloading, establishing a conserved Cbl-b→IRS-1 degradation axis that suppresses IGF-I/PI3K/Akt signaling to cause bone loss and muscle atrophy.

    Evidence Cbl-b KO denervation/unloading models; IRS-1 ubiquitination assay in primary cells; bone histomorphometry; peptide inhibitor blocking IRS-1 ubiquitination

    PMID:16734387 PMID:19546233

    Open questions at the time
    • Whether Cbl-b directly ubiquitinates IRS-1 or requires cofactors not fully resolved
    • therapeutic utility of peptide inhibitor in vivo not established
  9. 2007 High

    The biological consequence of Cbl-b loss for tumor immunity was demonstrated: Cbl-b-/- CD8+ T cells reject B7-negative tumors and resist TGF-β, while Cbl-b's RING finger E3 ligase activity was shown to suppress TLR4-MyD88 association and NF-κB signaling in innate immune cells.

    Evidence Tumor challenge and adoptive transfer in KO mice; TLR4-MyD88 co-IP; RING finger mutant NF-κB reporter assay; neutrophil TLR4 surface expression

    PMID:17364027 PMID:17618294

    Open questions at the time
    • Direct TLR4/MyD88 ubiquitination substrate identity not confirmed
    • whether TGF-β resistance involves a direct Cbl-b substrate was unknown
  10. 2009 High

    CARMA1 and NFATc1 were identified as Cbl-b substrates: Cbl-b monoubiquitinates CARMA1 to disrupt CARMA1-Bcl10 association and suppress NF-κB (mediating NKT cell anergy), while Cbl-b ubiquitinates NFATc1 for degradation as part of an NFATc1→Nur77→Cbl-b feedback loop limiting osteoclastogenesis.

    Evidence Co-IP; monoubiquitination and polyubiquitination assays; RING finger mutagenesis; Nur77 ChIP; bone phenotyping in KO mice

    PMID:19815501 PMID:25257814 PMID:26173181

    Open questions at the time
    • Mono- vs. polyubiquitination fate determinants unclear
    • structural basis of CARMA1-Bcl10 disruption by monoubiquitin not defined
  11. 2011 High

    A RING finger knock-in mouse definitively proved that all major T-cell regulatory functions of Cbl-b—including tolerance, anergy, autoimmunity prevention, and tumor rejection—require its catalytic E3 ubiquitin ligase activity rather than adaptor functions alone.

    Evidence E3-ligase-dead knock-in mouse phenocopying full KO in autoimmunity, anergy, and tumor rejection assays

    PMID:21248250

    Open questions at the time
    • Whether non-catalytic functions contribute in non-T-cell lineages remained untested
  12. 2012 High

    An E3-ligase-independent function of Cbl-b was uncovered: Cbl-b suppresses Nedd4-mediated K63-linked polyubiquitination and inactivation of PTEN, providing a distinct, non-catalytic mechanism by which Cbl-b restrains PI3K/Akt signaling in T cells.

    Evidence Pten ubiquitination analysis; Cbl-b/Nedd4 double KO epistasis; K63-linkage-specific assays; Akt activity measurement

    PMID:22763434

    Open questions at the time
    • How Cbl-b physically interferes with Nedd4-Pten interaction not structurally defined
    • whether this applies beyond T cells unknown
  13. 2014 High

    TAM receptor tyrosine kinases were identified as Cbl-b ubiquitination substrates in NK cells, establishing that Cbl-b limits NK-cell anti-metastatic activity; a TAM kinase inhibitor phenocopied Cbl-b loss, opening a pharmacological strategy.

    Evidence Ubiquitylation assay; E3-ligase-dead knock-in mice; in vivo metastasis models; TAM kinase inhibitor treatment

    PMID:24553136

    Open questions at the time
    • Which specific ubiquitin chain types on TAM receptors not defined
    • downstream effectors of TAM stabilization in NK cells incompletely mapped
  14. 2015 High

    Cbl-b was shown to ubiquitinate Foxp3 (with Stub1) for proteasomal degradation to regulate thymic Treg development, and to promote TrkA ubiquitination and degradation upon NGF stimulation, expanding the substrate repertoire to transcription factor and neurotrophin receptor signaling.

    Evidence Co-IP and ubiquitination assay for Foxp3; genetic epistasis (Cbl-b-/- × CD28-/-); temporal proteomics for TrkA; neurite outgrowth upon Cbl-b depletion

    PMID:25560411 PMID:25921289

    Open questions at the time
    • Relative contribution of Cbl-b vs. Stub1 to Foxp3 degradation not quantified
    • physiological role in neuronal TrkA signaling in vivo not established
  15. 2016 High

    CBLB was identified as a key negative regulator of innate antifungal immunity by ubiquitinating SYK, dectin-1, dectin-2, and dectin-3 downstream of C-type lectin receptors; Cbl-b targets ubiquitinated CLRs for ESCRT-mediated lysosomal degradation, and loss of Cbl-b protects mice from lethal systemic candidiasis.

    Evidence Ubiquitination assays; Cbl-b KO and double KO (Cbl-b × dectin) epistasis in C. albicans infection models; ESCRT knockdown; CLR trafficking analysis

    PMID:27428899 PMID:27428901 PMID:27432944

    Open questions at the time
    • Whether pharmacological Cbl-b inhibition recapitulates antifungal protection not tested
    • role in other fungal pathogens beyond C. albicans not established
  16. 2016 High

    Quantitative temporal interactomics of TCR-stimulated T cells identified CD5 as a key scaffold for CBLB-mediated ubiquitylation following TCR engagement, providing an unbiased map of the dynamic CBLB signaling complex.

    Evidence AP-MS time course over 600 s of TCR stimulation with biochemical validation

    PMID:27474268

    Open questions at the time
    • Functional consequence of CD5-scaffolded Cbl-b activity not fully dissected
    • direct vs. indirect interactions in the complex not resolved for all partners
  17. 2019 High

    TAM receptor-mediated phosphorylation of Cbl-b at Y133 and Y363 was shown to activate Cbl-b in NK cells, with Gas6/TAM ligation triggering Cbl-b-dependent degradation of the adaptor LAT1 to suppress NK-cell effector functions.

    Evidence Gas6 ligation; Y133/Y363 phosphosite mutagenesis; Cbl-b KO NK cells; LAT1 degradation assay

    PMID:31531847

    Open questions at the time
    • Whether Y133/Y363 phosphorylation equally regulates Cbl-b in T cells and myeloid cells not tested
    • kinase(s) besides TAM receptors that phosphorylate these sites not mapped
  18. 2020 High

    Cbl-b was found to ubiquitinate NMDA receptor subunit GluN2B in spinal dorsal horn neurons via its TKB domain, with inflammation-induced Y363 dephosphorylation impairing Cbl-b–GluN2B binding and enabling synaptic GluN2B accumulation, linking Cbl-b to nociceptive sensitization.

    Evidence Co-IP and ubiquitination assay; phosphomimetic Y363 mutagenesis; in vivo knockdown; electrophysiology of synaptic NMDAR currents

    PMID:32606037

    Open questions at the time
    • Identity of the phosphatase dephosphorylating Y363 in neurons not determined
    • behavioral pain outcomes of Cbl-b manipulation not fully characterized
  19. 2021 High

    CRISPR-mediated Cbl-b deletion was shown to rescue exhausted CD8+ tumor-infiltrating lymphocytes and CAR T cells, reducing PD1+Tim3+ populations and restoring effector function, establishing Cbl-b as a druggable checkpoint for reversing T-cell exhaustion.

    Evidence CRISPR-Cas9 Cbl-b KO in CD8+ T cells and CAR T cells; syngeneic MC38 tumor model; cytokine and killing assays

    PMID:33462140

    Open questions at the time
    • Direct substrate(s) linking Cbl-b to the exhaustion transcriptional program not identified
    • long-term safety of Cbl-b deletion in therapeutic T cells not assessed
  20. 2023 High

    A co-crystal structure of Cbl-b with a small-molecule inhibitor revealed that the compound acts as an intramolecular glue bridging the TKBD and LHR domains (not the RING domain), locking Cbl-b in an autoinhibited conformation—providing the first structural basis for pharmacological Cbl-b inhibition.

    Evidence X-ray crystallography; SPR and thermal shift biophysical assays; cellular ubiquitination assay

    PMID:38104184

    Open questions at the time
    • In vivo efficacy and selectivity of TKBD-LHR glue inhibitors not yet demonstrated
    • whether this mechanism generalizes to other Cbl family members unknown
  21. 2023 High

    Cbl-b was found to form a TCR-induced complex with the pH-sensitive phosphatase STS1 via a proline motif, with STS1 dephosphorylating Cbl-b-associated phosphoproteins; this complex renders T cells sensitive to acidic tumor microenvironments, and loss of either partner enhances anti-tumor immunity.

    Evidence Co-IP with proline-motif mutagenesis; STS1 and Cbl-b KO mice; pH sensitivity assays; tumor growth experiments

    PMID:38091950

    Open questions at the time
    • Which specific phosphoproteins STS1 dephosphorylates in the Cbl-b complex not mapped
    • structural basis of pH sensing by STS1-Cbl-b not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key remaining questions include: the structural basis of Cbl-b substrate selectivity across its >15 known substrates; whether non-catalytic functions (e.g., PTEN protection) operate broadly beyond T cells; the identity of the E3 ligase(s) that ubiquitinate Cbl-b itself for degradation upon CD28 signaling; and whether pharmacological Cbl-b inhibitors achieve selective immune activation without autoimmune toxicity in vivo.
  • No comprehensive structural model for multi-substrate recognition
  • E3 ligase targeting Cbl-b for degradation unidentified
  • in vivo therapeutic window of Cbl-b inhibitors not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 14 GO:0016874 ligase activity 5 GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 2
Localization
GO:0005829 cytosol 4 GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 13 R-HSA-392499 Metabolism of proteins 9 R-HSA-162582 Signal Transduction 7
Partners
CIN85CLEC7AGRB2NEDD4PIK3R1STS1SYKVAV1
Complex memberships
Cbl-b–CIN85–endophilin complexCbl-b–STS1 complexDR5–Cbl-b/c-Cbl–TRAF2 complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Cbl-b loss uncouples T-cell proliferation, IL-2 production, and Vav1 phosphorylation from the requirement for CD28 co-stimulation, identifying Cbl-b as a key regulator of T-cell activation thresholds in mature lymphocytes. Gene-targeted knockout mice; hyperproliferation and cytokine production assays; Vav1 phosphorylation analysis Nature High 10646608 10646609
2000 Cbl-b selectively suppresses TCR-mediated Vav (guanine nucleotide exchange factor for Rac1/Rho/CDC42) activation to regulate CD28 dependence of T-cell activation; Cbl-b-null mutation fully restores T-cell-dependent antibody responses in CD28-deficient mice. Genetic epistasis (cbl-b-/- × CD28-/- double mutant mice); Vav activation assays; antibody response measurements Nature High 10646609
2000 Cbl-b interacts with and induces ubiquitin conjugation to the p85 regulatory subunit of PI3K; the RING finger domain is essential for p85 ubiquitination, and a distal proline-rich region of Cbl-b binds the SH3 domain of p85. Co-immunoprecipitation; in vitro ubiquitination assay; RING finger loss-of-function mutagenesis; deletion mapping The Journal of biological chemistry High 11087752
2001 Cbl-b negatively regulates p85 (PI3K regulatory subunit) in a proteolysis-independent manner by controlling its recruitment to CD28 and TCR-zeta, requiring Cbl-b E3 ubiquitin ligase activity; enhanced activation of Cbl-b-/- T cells is suppressed by PI3K inhibition. Ubiquitination assay; PI3K inhibitor rescue; co-immunoprecipitation with CD28 and TCR-zeta Nature immunology High 11526404
2001 Cbl-b is ubiquitinated and degraded upon EGFR activation; EGF-induced Cbl-b degradation requires intact RING finger and tyrosine kinase binding domains and binding to activated EGFR; Cbl-b mediates coordinated degradation of the EGFR signaling complex including Grb2 and Shc via lysosomal and proteasomal pathways. EGF stimulation; RING finger and TKB domain mutagenesis; lysosomal/proteasomal inhibitors; Western blot for complex components The Journal of biological chemistry High 11375397
2002 CD28 co-stimulation selectively induces greater ubiquitination and degradation of Cbl-b than CD3 stimulation alone, establishing that CD28 regulates the T-cell activation threshold partly by promoting Cbl-b ubiquitination and degradation. Ubiquitination assay; stimulation of wild-type vs. CD28-deficient T cells; Western blot for Cbl-b levels Journal of immunology High 12193687
2002 CIN85 binds to the carboxyl terminus of Cbl-b; ligand-induced phosphorylation of Cbl-b increases CIN85 interaction; CIN85–Cbl-b binding is required for Cbl-b-mediated EGFR internalization (but dispensable for EGFR polyubiquitination), defining a CIN85/endophilin-dependent endocytic pathway. Co-immunoprecipitation; dominant-negative CIN85 interference; EGFR internalization assay; ubiquitination assay The Journal of biological chemistry High 12177062
2002 Cbl-b positively regulates BCR-mediated Ca2+ signaling by interacting with PLC-γ2 and facilitating its association with Btk and BLNK; Cbl-b is required for Btk-dependent sustained intracellular Ca2+ increase; both N-terminal TKB domain and C-terminal half of Cbl-b are essential. Cbl-b-deficient DT40 B cells; overexpression in WEHI-231 cells; Ca2+ mobilization assay; co-immunoprecipitation of PLC-γ2/Btk/BLNK complex; domain deletion mutagenesis The Journal of experimental medicine High 12093870
2004 Cbl-b is upregulated in T cells after tolerizing signals and is essential for T-cell anergy induction; loss of Cbl-b rescues reduced calcium mobilization of anergic T cells, attributable to Cbl-b-mediated regulation of PLCγ-1 phosphorylation. In vitro and in vivo T cell tolerance assays in Cbl-b-/- mice; calcium mobilization assay; PLCγ-1 phosphorylation analysis Immunity High 15308098
2004 Cbl-b-/- effector T cells are resistant to suppression by CD4+CD25+ regulatory T cells and by TGF-β in vitro, despite normal levels of TGF-β receptor II and normal Smad3 phosphorylation, indicating the resistance operates downstream of TGF-β receptor signaling. In vitro T cell suppression assays; TGF-β receptor expression analysis; Smad3 phosphorylation assay Journal of immunology Medium 15240694
2007 Cblb-/- CD8+ T cells are resistant to TGF-β suppression and do not require CD28 costimulation for activation in vitro; in vivo, Cblb-/- mice efficiently reject B7-negative tumors via massively infiltrating CD8+ T cells; adoptive transfer of purified Cblb-/- CD8+ T cells eradicates established tumors. Knockout mice; in vitro TGF-β suppression assay; tumor challenge with B7-negative cell lines; adoptive transfer of CD8+ T cells The Journal of clinical investigation High 17364027
2007 Cblb controls the association between TLR4 and the intracellular adaptor MyD88 and regulates TLR4 surface expression on neutrophils; E3 ligase activity (not adaptor function) of Cblb is required to suppress NF-κB-mediated inflammatory responses to LPS. Co-immunoprecipitation of TLR4-MyD88; NF-κB reporter assay with wild-type vs. RING-finger-mutant Cblb; flow cytometry of TLR4 surface levels on Cblb-/- neutrophils Nature medicine High 17618294
2007 Cbl-b interacts with Pseudomonas exotoxin T (ExoT) and promotes its polyubiquitination and proteasomal degradation in host cells; Cbl-b (but not c-Cbl) is specifically required in vivo to limit bacterial dissemination mediated by ExoT. Co-immunoprecipitation of Cbl-b with ExoT and Crk; proteasomal inhibitor experiments; in vivo mouse infection models with Cblb-/- mice The Journal of clinical investigation High 17235393
2009 Upon unloading stress, Cbl-b is induced in skeletal muscle and directly ubiquitinates IRS-1, targeting it for degradation; loss of IRS-1 activates FOXO3-dependent atrogin-1/MAFbx induction; Cbl-b-/- mice are resistant to unloading-induced atrophy. Co-immunoprecipitation of Cbl-b with IRS-1; ubiquitination assay; KO mice subjected to hindlimb unloading; peptide inhibitor (pY608-IRS-1 mimetic) blocks IRS-1 ubiquitination Molecular and cellular biology High 19546233
2009 Cbl-b interacts with CARMA1 and promotes its monoubiquitination; this monoubiquitination disrupts CARMA1-Bcl10 complex formation (without affecting CARMA1 stability), thereby suppressing NF-κB activation and mediating NKT cell anergy; Cbl-b RING finger activity is critical. Co-immunoprecipitation; monoubiquitination assay; RING finger mutant analysis; CARMA1-/- NKT cell functional analysis Proceedings of the National Academy of Sciences of the United States of America High 19815501
2009 Loss of Cbl-b increases osteoclast bone-resorbing activity and in vitro differentiation, and enhances RANKL-induced NF-κB, ERK, and p38 signaling; rescue by re-expressing Cbl-b (but not by c-Cbl) requires functional TKB and RING finger domains. Cbl-b-/- mice; in vitro bone resorption assay; RANKL signaling analysis; rescue by wild-type vs. domain-mutant Cbl-b re-expression Journal of bone and mineral research High 19257814
2011 Selective genetic inactivation of Cbl-b E3 ligase activity (RING finger knock-in mutation) phenocopies total Cbl-b ablation in T-cell hyperactivation, spontaneous autoimmunity, impaired T-cell anergy, and spontaneous tumor rejection, demonstrating the catalytic E3 ligase activity is essential for all Cbl-b T-cell regulatory functions in vivo. RING finger knock-in mouse (E3 ligase-dead); comparison with total Cbl-b KO; autoimmunity scoring; tumor rejection assays; T-cell anergy induction assays Journal of immunology High 21248250
2012 Cbl-b suppresses Pten inactivation (rather than directly inhibiting PI3K) in T cells by impeding Nedd4-mediated K63-linked polyubiquitination of Pten at K13; elevated Akt in Cbl-b-/- T cells is due to heightened Pten inactivation; this function is independent of Cbl-b's own E3 ligase activity. Pten ubiquitination analysis; Nedd4 co-immunoprecipitation; double KO (Cbl-b-/- × Nedd4-/-); Akt activity measurement; ubiquitin linkage-specific assays Cell reports High 22763434
2014 Cbl-b ubiquitylates TAM receptor tyrosine kinases (Tyro3, Axl, Mertk) in NK cells, limiting NK cell anti-metastatic activity; genetic deletion or E3 ligase inactivation of Cbl-b licenses NK cells to reject metastatic tumors; a TAM kinase inhibitor phenocopies Cbl-b loss. Ubiquitylation assay identifying TAM receptors as Cbl-b substrates; E3-ligase-dead knock-in mice; in vivo tumor metastasis models; TAM kinase inhibitor treatment Nature High 24553136
2014 Cbl-b ubiquitylates IGF-IR in gastric cancer cells leading to its degradation, thereby inhibiting the Akt/ERK-miR-200c-ZEB2 axis and suppressing IGF-I-induced epithelial-mesenchymal transition. Cbl-b shRNA knockdown; co-immunoprecipitation; ubiquitination assay; Akt/ERK inhibitors; miR-200c and ZEB2 expression analysis Molecular cancer Medium 24885194
2015 Upon NGF stimulation of neuroblastoma cells, TrkA recruits Cbl-b, which becomes phosphorylated and ubiquitylated; Cbl-b promotes TrkA ubiquitylation and degradation; Cbl-b depletion increases ERK phosphorylation and neurite outgrowth. Quantitative interactome/proteome/phosphoproteome mass spectrometry; Cbl-b depletion; neurite outgrowth measurement Science signaling High 25921289
2015 Cbl-b binds Foxp3 upon TCR stimulation and, together with Stub1, targets Foxp3 for ubiquitination and proteasomal degradation, thereby regulating thymic Treg development; proteasome inhibition rescues defective tTreg development in CD28-/- mice. Co-immunoprecipitation of Cbl-b with Foxp3; ubiquitination assay; Cbl-b-/- × CD28-/- genetic rescue; proteasome inhibitor rescue of tTreg development Journal of immunology High 25560411
2015 NFATc1 induces Nur77 expression during osteoclast differentiation; Nur77 transcriptionally upregulates Cbl-b; Cbl-b then triggers NFATc1 protein degradation via ubiquitination, creating a self-limiting NFATc1→Nur77→Cbl-b→NFATc1 feedback loop that prevents excessive osteoclastogenesis. Genetic KO (Nur77-/-); ChIP/reporter assay linking Nur77 to Cbl-b promoter; ubiquitination assay showing Cbl-b ubiquitinates NFATc1; bone mass phenotyping eLife High 26173181
2016 CBLB associates with SYK and ubiquitinates SYK, dectin-1, and dectin-2 following fungal recognition via C-type lectin receptors; CBLB deficiency results in increased inflammasome activation, enhanced ROS production, and enhanced fungal killing. Co-immunoprecipitation of CBLB with SYK/dectin-1/dectin-2; ubiquitination assay; Cblb-/- macrophage/DC functional assays; lethal C. albicans infection model Nature medicine High 27428899 27428901
2016 CBLB directs polyubiquitination of dectin-1 and dectin-2 and their downstream kinase SYK, inhibiting dectin-mediated innate immune responses; dectin-1 and dectin-2 deficiency in Cblb-/- mice abrogates the protection against systemic C. albicans infection. Ubiquitination assay; genetic epistasis (Cblb-/- × dectin-1-/- or dectin-2-/- double KO); in vivo lethal C. albicans infection model Nature medicine High 27428899
2016 Cbl-b mediates ubiquitination of activated Dectin-2 and Dectin-3 via adapter FcR-γ and kinase Syk in a Syk-dependent manner; ubiquitinated CLRs are sorted into lysosomes via the ESCRT system for degradation. Co-immunoprecipitation of Cbl-b with FcR-γ/Syk/CLRs; ubiquitination assay; ESCRT subunit knockdown; CLR degradation analysis The Journal of experimental medicine High 27432944
2016 TCR stimulation dynamics of CBL and CBLB signaling complexes were characterized by affinity purification coupled to quantitative mass spectrometry; CD5 transmembrane receptor was identified as a key scaffold for CBLB-mediated ubiquitylation following TCR engagement. Affinity purification coupled to quantitative MS over 600 s TCR stimulation time course; biochemical validation of CD5 as a scaffold Molecular systems biology High 27474268
2019 TAM receptors (Tyro3, Axl, Mer) phosphorylate Cbl-b at tyrosine residues Y133 and Y363 to activate it; Gas6-mediated TAM receptor ligation suppresses NK-cell functions (IFN-γ production, degranulation) via Cbl-b; Cbl-b promotes degradation of LAT1 (transmembrane adaptor) in response to Gas6. TAM receptor ligation with Gas6; phosphorylation site mutagenesis (Y133, Y363); Cbl-b KO NK cells; LAT1 degradation assay European journal of immunology High 31531847
2020 Cbl-b is enriched in spinal cord dorsal horn neurons; it interacts with GluN2B via its N-terminal TKB domain and ubiquitinates GluN2B, reducing synaptic GluN2B-containing NMDARs; peripheral inflammation induces dephosphorylation of Cbl-b at Y363, impairing its binding to and ubiquitylation of GluN2B and enabling GluN2B reappearance at synapses. Co-immunoprecipitation; ubiquitination assay; in vivo Cbl-b knockdown; phosphomimetic Cbl-b mutant expression; electrophysiology of synaptic currents Science signaling High 32606037
2023 The co-crystal structure of Cbl-b with inhibitor C7683 (analogue of Nx-1607) reveals the compound binds both the TKBD and LHR domains but not the RING domain, locking Cbl-b in an inactive conformation by acting as an intramolecular glue; confirmed by biophysical assays. X-ray crystallography (co-crystal structure); biophysical binding assays (SPR, thermal shift); cellular ubiquitination assay Communications biology High 38104184
2023 TCR stimulation induces a molecular complex between Cbl-b and the pH-sensitive unconventional phosphatase STS1 via a proline motif in Cbl-b interacting with the STS1 SH3 domain; STS1 dephosphorylates Cbl-b-interacting phosphoproteins; deficiency of STS1 or Cbl-b reduces T-cell sensitivity to acidic environments and promotes anti-tumor T-cell activity. Co-immunoprecipitation; STS1 and Cbl-b KO mice; proline-motif mutagenesis; in vitro and in vivo pH sensitivity assays; tumor growth experiments Immunity High 38091950
2003 Cbl-b undergoes tyrosine phosphorylation and plasma membrane translocation in response to insulin in adipocytes; it constitutively associates with CAP and interacts with Crk upon insulin stimulation; Cbl proteins form homo- and heterodimers via a conserved leucine zipper domain required for APS interaction and tyrosine phosphorylation. Phosphorylation assays in 3T3-L1 adipocytes; co-immunoprecipitation with CAP and Crk; leucine zipper dimerization mutagenesis; membrane fractionation The Journal of biological chemistry Medium 12842890
2006 Cbl-b is upregulated in osteoblastic cells after denervation and ubiquitinates IRS-1, promoting its degradation, thereby suppressing IGF-I signaling (PI3K, Akt-1) in osteoblasts and causing reduced bone formation; Cbl-b-/- mice maintain bone mass after denervation. Cbl-b-/- denervation model; IRS-1 ubiquitination assay in primary osteoblasts; Western blot for IGF-I signaling; bone histomorphometry Journal of bone and mineral research High 16734387
2023 Cbl-b and Cbl-b interact with EGFR through distinct modes: Cbl-b preferentially binds pY1045 of EGFR directly, while c-Cbl relies mainly on Grb2-dependent indirect binding; each operates independently to jointly control EGFR ubiquitination, endocytic trafficking, and chemotaxis signaling. Inducible expression of E3-ligase-dead Cbl-b and c-Cbl mutants; EGFR ubiquitination and degradation assays; chemotaxis migration assay; cells with differential Cbl-b endogenous levels Molecular biology of the cell High 37903221
1999 Cbl-b is phosphorylated and recruited to EGFR upon EGF stimulation and binds Grb2; overexpression of Cbl-b in EGFR-dependent cells decreases AKT activation amplitude/duration and shortens MAP kinase/JNK activation, inhibiting EGF-induced cell growth and promoting apoptosis. Overexpression in 32D/EGFR cells; growth assays; AKT and MAPK activation time course; apoptosis assay Oncogene Medium 10086340
1998 CBLB is phosphorylated on tyrosine following FLT3 ligand or IL-7 stimulation in pro-B cells; tyrosine-phosphorylated SHC and p85 of PI3K associate with CBLB upon FL or IL-7 treatment; CBLB constitutively binds GRB2 predominantly through GRB2's N-terminal SH3 domain. Tyrosine phosphorylation assay; co-immunoprecipitation of SHC, p85, GRB2 with CBLB The Journal of biological chemistry Medium 9614102
2018 CBLB forms a complex with CD81 and calpain-5 (CAPN5) in human liver cells; CBLB is required for a post-binding, pre-replication step in HCV entry; CBLB knockout reduces susceptibility to all tested HCV genotypes but not to other enveloped viruses. Quantitative proteomics of CD81 interactome; CBLB/CAPN5 knockout; HCV infection assay across genotypes PLoS pathogens Medium 30024968
2017 DR5-Cbl-b/c-Cbl-TRAF2 form a complex in TRAIL-resistant gastric cancer cells; Cbl-b and c-Cbl serve as adaptors linking DR5 to TRAF2; TRAIL-induced caspase-8 translocation into this complex leads to TRAF2-mediated K48-linked polyubiquitination and proteasomal degradation of caspase-8, inhibiting apoptosis. Co-immunoprecipitation; ubiquitination assay (K48-linkage-specific); TRAF2 and Cbl-b knockdown; proteasome inhibitor (bortezomib) rescue Molecular oncology Medium 28972304
2022 Cbl-b and c-Cbl ubiquitinate STAT5a and STAT5b in dendritic cells to promote their degradation and cell apoptosis; Cbl-b mediates K27-linked ubiquitination of STAT5a at K164, while c-Cbl induces K29-linked ubiquitination of STAT5a K696 and K27-linked ubiquitination of STAT5b K140 and K694. DC-specific double KO mice (Cbl-b-/-×c-Cblflox/flox CD11c-Cre); STAT5 ubiquitination assays with linkage-specific ubiquitin mutants; site-directed mutagenesis of STAT5 lysine residues Cell death discovery Medium 35354799
2021 Cbl-b is upregulated in exhausted (PD1+Tim3+) CD8+ tumor-infiltrating lymphocytes; CRISPR-Cas9-mediated deletion of Cbl-b in CD8+ T cells and CAR T cells restores effector function of exhausted cells, reduces PD1+Tim3+ populations, and increases IFN-γ/TNF-α production and tumor cell killing. RNA-seq of TILs; syngeneic MC38 tumor model; CRISPR-Cas9 Cbl-b KO in CAR T cells; tumor growth and cytokine assays Journal for immunotherapy of cancer High 33462140

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b. Nature 544 10646608
2000 Cbl-b regulates the CD28 dependence of T-cell activation. Nature 496 10646609
2014 The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature 373 24553136
2004 Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction. Immunity 279 15308098
2001 Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells. Nature immunology 236 11526404
2005 c-Cbl and Cbl-b ubiquitin ligases: substrate diversity and the negative regulation of signalling responses. The Biochemical journal 214 16212556
2000 Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. The Journal of biological chemistry 160 11087752
2009 Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading. Molecular and cellular biology 149 19546233
2002 Cblb is a major susceptibility gene for rat type 1 diabetes mellitus. Nature genetics 146 12118252
2002 Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria. Human molecular genetics 134 12471062
2010 Variants within the immunoregulatory CBLB gene are associated with multiple sclerosis. Nature genetics 131 20453840
2011 CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia. Blood 128 21346257
2001 Cbl-b-dependent coordinated degradation of the epidermal growth factor receptor signaling complex. The Journal of biological chemistry 122 11375397
2002 Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination. Journal of immunology (Baltimore, Md. : 1950) 121 12193687
2007 Spontaneous tumor rejection by cbl-b-deficient CD8+ T cells. The Journal of experimental medicine 120 17403934
2018 miR-27b-3p inhibits proliferation and potentially reverses multi-chemoresistance by targeting CBLB/GRB2 in breast cancer cells. Cell death & disease 119 29416005
2021 Deletion of Cbl-b inhibits CD8+ T-cell exhaustion and promotes CAR T-cell function. Journal for immunotherapy of cancer 108 33462140
2004 Resistance to CD4+CD25+ regulatory T cells and TGF-beta in Cbl-b-/- mice. Journal of immunology (Baltimore, Md. : 1950) 104 15240694
1999 cbl-b inhibits epidermal growth factor receptor signaling. Oncogene 104 10086340
2002 CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases. The Journal of biological chemistry 101 12177062
2007 Ablation of Cbl-b provides protection against transplanted and spontaneous tumors. The Journal of clinical investigation 98 17364027
2016 Inhibition of CBLB protects from lethal Candida albicans sepsis. Nature medicine 93 27428901
2007 E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury. Nature medicine 85 17618294
2011 Essential role of E3 ubiquitin ligase activity in Cbl-b-regulated T cell functions. Journal of immunology (Baltimore, Md. : 1950) 80 21248250
2002 Cbl and Cbl-b in T-cell regulation. Trends in immunology 79 11864842
2016 Targeting CBLB as a potential therapeutic approach for disseminated candidiasis. Nature medicine 78 27428899
2015 Modulation of Immune Cell Functions by the E3 Ligase Cbl-b. Frontiers in oncology 78 25815272
2010 Abrogating Cbl-b in effector CD8(+) T cells improves the efficacy of adoptive therapy of leukemia in mice. The Journal of clinical investigation 77 20890046
2018 Regulation of immune responses by E3 ubiquitin ligase Cbl-b. Cellular immunology 74 30442330
2014 Ubiquitin ligase Cbl-b represses IGF-I-induced epithelial mesenchymal transition via ZEB2 and microRNA-200c regulation in gastric cancer cells. Molecular cancer 73 24885194
2003 The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport. The Journal of biological chemistry 70 12842890
2009 Mechanisms of NKT cell anergy induction involve Cbl-b-promoted monoubiquitination of CARMA1. Proceedings of the National Academy of Sciences of the United States of America 63 19815501
2015 Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation. Science signaling 61 25921289
2014 E3 ubiquitin ligase Cbl-b in innate and adaptive immunity. Cell cycle (Georgetown, Tex.) 61 24875217
2012 E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity. Cell reports 60 22763434
2023 Targeting Cbl-b in cancer immunotherapy. Journal for immunotherapy of cancer 56 36750253
2020 β-Elemene inhibits the metastasis of multidrug-resistant gastric cancer cells through miR-1323/Cbl-b/EGFR pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 53 32199253
2015 Clinical significance of tumor-infiltrating immune cells focusing on BTLA and Cbl-b in patients with gallbladder cancer. Cancer science 53 26395180
2013 T cell activation threshold regulated by E3 ubiquitin ligase Cbl-b determines fate of inducible regulatory T cells. Journal of immunology (Baltimore, Md. : 1950) 51 23749633
2012 Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells. Journal of cancer research and clinical oncology 51 22447040
2016 E3 ubiquitin ligase Cbl-b negatively regulates C-type lectin receptor-mediated antifungal innate immunity. The Journal of experimental medicine 49 27432944
2018 Reactive oxygen species upregulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells. American journal of physiology. Cell physiology 48 29513566
2012 TRAIL-activated EGFR by Cbl-b-regulated EGFR redistribution in lipid rafts antagonises TRAIL-induced apoptosis in gastric cancer cells. European journal of cancer (Oxford, England : 1990) 48 22456178
2012 Adoptive transfer of siRNA Cblb-silenced CD8+ T lymphocytes augments tumor vaccine efficacy in a B16 melanoma model. PloS one 48 22962608
2010 Cbl-b in T-cell activation. Seminars in immunopathology 48 20458601
2009 Reversal of P-glycoprotein-mediated multi-drug resistance by the E3 ubiquitin ligase Cbl-b in human gastric adenocarcinoma cells. The Journal of pathology 46 19274672
1998 The CBL-related protein CBLB participates in FLT3 and interleukin-7 receptor signal transduction in pro-B cells. The Journal of biological chemistry 46 9614102
2018 Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB. PLoS pathogens 45 30024968
2007 Methylmalonic acidaemia: examination of genotype and biochemical data in 32 patients belonging to mut, cblA or cblB complementation group. Journal of inherited metabolic disease 44 17957493
2002 Cbl-b positively regulates Btk-mediated activation of phospholipase C-gamma2 in B cells. The Journal of experimental medicine 44 12093870
2016 Co-recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies CD5 as a key regulator of TCR-induced ubiquitylation. Molecular systems biology 43 27474268
2007 Cbl-b regulates antigen-induced TCR down-regulation and IFN-gamma production by effector CD8 T cells without affecting functional avidity. Journal of immunology (Baltimore, Md. : 1950) 43 18025165
2015 E3 Ubiquitin Ligase Cbl-b Regulates Thymic-Derived CD4+CD25+ Regulatory T Cell Development by Targeting Foxp3 for Ubiquitination. Journal of immunology (Baltimore, Md. : 1950) 41 25560411
2010 Cbl-b and itch: key regulators of peripheral T-cell tolerance. Cancer research 41 20395198
2010 T-cell regulation by casitas B-lineage lymphoma (Cblb) is a critical failsafe against autoimmune disease due to autoimmune regulator (Aire) deficiency. Proceedings of the National Academy of Sciences of the United States of America 41 20668237
2009 Loss of Cbl-b increases osteoclast bone-resorbing activity and induces osteopenia. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 41 19257814
2006 Mutation and biochemical analysis of patients belonging to the cblB complementation class of vitamin B12-dependent methylmalonic aciduria. Molecular genetics and metabolism 41 16410054
2017 E3 Ubiquitin Ligase Cbl-b Prevents Tumor Metastasis by Maintaining the Epithelial Phenotype in Multiple Drug-Resistant Gastric and Breast Cancer Cells. Neoplasia (New York, N.Y.) 40 28334634
2006 Ubiquitin ligase Cbl-b downregulates bone formation through suppression of IGF-I signaling in osteoblasts during denervation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 40 16734387
2005 CBLB variants in type 1 diabetes and their genetic interaction with CTLA4. Journal of leukocyte biology 39 15629882
2011 Th3 immune responses in the progression of leprosy via molecular cross-talks of TGF-β, CTLA-4 and Cbl-b. Clinical immunology (Orlando, Fla.) 37 21807564
2005 Differential control of CD28-regulated in vivo immunity by the E3 ligase Cbl-b. Journal of immunology (Baltimore, Md. : 1950) 37 15661906
2015 Ionizing radiation-inducible miR-30e promotes glioma cell invasion through EGFR stabilization by directly targeting CBL-B. The FEBS journal 35 25691332
2007 The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T-mediated virulence. The Journal of clinical investigation 35 17235393
2020 Bta-miR-223 Targeting CBLB Contributes to Resistance to Staphylococcus aureus Mastitis Through the PI3K/AKT/NF-κB Pathway. Frontiers in veterinary science 32 33195489
2007 Regulation of peripheral T cell tolerance by the E3 ubiquitin ligase Cbl-b. Seminars in immunology 32 17391982
2021 CBLB ablation with CRISPR/Cas9 enhances cytotoxicity of human placental stem cell-derived NK cells for cancer immunotherapy. Journal for immunotherapy of cancer 31 33741730
2013 Pharmacological chaperones as a potential therapeutic option in methylmalonic aciduria cblB type. Human molecular genetics 31 23674520
2019 TAM receptors attenuate murine NK-cell responses via E3 ubiquitin ligase Cbl-b. European journal of immunology 30 31531847
2010 Rantes secreted from macrophages disturbs skeletal muscle regeneration after cardiotoxin injection in Cbl-b-deficient mice. Muscle & nerve 28 21254087
2017 DR5-Cbl-b/c-Cbl-TRAF2 complex inhibits TRAIL-induced apoptosis by promoting TRAF2-mediated polyubiquitination of caspase-8 in gastric cancer cells. Molecular oncology 27 28972304
2019 Bufalin induces protective autophagy by Cbl-b regulating mTOR and ERK signaling pathways in gastric cancer cells. Cell biology international 26 30468278
2015 Cbl-b inhibits P-gp transporter function by preventing its translocation into caveolae in multiple drug-resistant gastric and breast cancers. Oncotarget 26 25788263
2011 Replication study of 10 genes showing evidence for association with multiple sclerosis: validation of TMEM39A, IL12B and CBLB [correction of CLBL] genes. Multiple sclerosis (Houndmills, Basingstoke, England) 25 22194214
2006 Impact of cblB mutations on the function of ATP:cob(I)alamin adenosyltransferase in disorders of vitamin B12 metabolism. Molecular genetics and metabolism 25 16439175
2004 Haplotype tag single nucleotide polymorphism analysis of the human orthologues of the rat type 1 diabetes genes Ian4 (Lyp/Iddm1) and Cblb. Diabetes 25 14747305
2023 The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition. Communications biology 24 38104184
2014 Loss of Cbl-PI3K interaction enhances osteoclast survival due to p21-Ras mediated PI3K activation independent of Cbl-b. Journal of cellular biochemistry 24 24470255
2013 Soy Glycinin Contains a Functional Inhibitory Sequence against Muscle-Atrophy-Associated Ubiquitin Ligase Cbl-b. International journal of endocrinology 24 23762056
2012 Releasing the brake: targeting Cbl-b to enhance lymphocyte effector functions. Clinical & developmental immunology 24 22550535
2023 TCR signaling promotes formation of an STS1-Cbl-b complex with pH-sensitive phosphatase activity that suppresses T cell function in acidic environments. Immunity 23 38091950
2020 Ubiquitination and functional modification of GluN2B subunit-containing NMDA receptors by Cbl-b in the spinal cord dorsal horn. Science signaling 23 32606037
2018 MicroRNA-29b-2-5p inhibits cell proliferation by directly targeting Cbl-b in pancreatic ductal adenocarcinoma. BMC cancer 23 29940895
2015 N-myristoylated ubiquitin ligase Cbl-b inhibitor prevents on glucocorticoid-induced atrophy in mouse skeletal muscle. Archives of biochemistry and biophysics 23 25689493
2010 Functional and structural analysis of five mutations identified in methylmalonic aciduria cblB type. Human mutation 23 20556797
2007 The Cbl-b RING finger domain has a limited role in regulating inflammatory cytokine production by IgE-activated mast cells. Molecular immunology 23 17868870
2006 Enhancement of long-term memory retention and short-term synaptic plasticity in cbl-b null mice. Proceedings of the National Academy of Sciences of the United States of America 23 16549761
2015 Nur77 prevents excessive osteoclastogenesis by inducing ubiquitin ligase Cbl-b to mediate NFATc1 self-limitation. eLife 22 26173181
2014 A multiple sclerosis-associated variant of CBLB links genetic risk with type I IFN function. Journal of immunology (Baltimore, Md. : 1950) 22 25261476
2013 Cbl-b enhances sensitivity to 5-fluorouracil via EGFR- and mitochondria-mediated pathways in gastric cancer cells. International journal of molecular sciences 22 24351824
2011 Reinforcement of cancer immunotherapy by adoptive transfer of cblb-deficient CD8+ T cells combined with a DC vaccine. Immunology and cell biology 22 21383769
2017 Cblb-deficient T cells are less susceptible to PD-L1-mediated inhibition. Oncotarget 21 28611299
2012 Cbl-b-dependent degradation of FLIP(L) is involved in ATO-induced autophagy in leukemic K562 and gastric cancer cells. FEBS letters 20 22884570
2022 Ablation of Cbl-b and c-Cbl in dendritic cells causes spontaneous liver cirrhosis via altering multiple properties of CD103+ cDC1s. Cell death discovery 19 35354799
2021 Cbl-b deficiency prevents functional but not phenotypic T cell anergy. The Journal of experimental medicine 19 33974042
2011 Visualizing the role of Cbl-b in control of islet-reactive CD4 T cells and susceptibility to type 1 diabetes. Journal of immunology (Baltimore, Md. : 1950) 19 21248249
2009 Activation of T cells: releasing the brakes by proteolytic elimination of Cbl-b. Science signaling 19 19549983
2023 Cbl and Cbl-b independently regulate EGFR through distinct receptor interaction modes. Molecular biology of the cell 18 37903221
2018 Cbl-b deficiency provides protection against UVB-induced skin damage by modulating inflammatory gene signature. Cell death & disease 18 30082827
2014 Ubiquitin ligase Cbl-b and obesity-induced insulin resistance. Endocrine journal 18 24614797