Recombinant Mouse E3 ubiquitin-protein ligase CBL-B (Cblb), partial

1. The establishment of a new model of concurrent tissue-selective CBL/CBL-B deletion should allow a clear assessment of the tumor-intrinsic roles of CBL/CBL-B in non-myeloid malignancies and help test the potential for CBL/CBL-B inactivation in immunotherapy of tumors. PMID: 27276677
2. GSK3 catalyzes two previously unreported phosphorylation events at Ser(476) and Ser(480) of Cbl-b. Constitutive activation of PKB in vivo results in a loss of tolerance that is mediated through the downregulation of Cbl-b. The PI3K-PKB-GSK-3 pathway is a novel regulatory axis that is important for controlling the decision between T cell activation and tolerance via Cbl-b. PMID: 29109121
3. These studies reveal a novel, cell-autonomous requirement of CBL and CBL-B in epithelial stem cell maintenance during organ development and remodeling through modulation of mTOR signaling. PMID: 28100467
4. CBLB directs polyubiquitination of dectin-1 and dectin-2, two key pattern-recognition receptors for sensing Candida albicans, and their downstream kinase SYK, thus inhibiting dectin-1- and dectin-2-mediated innate immune responses. PMID: 27428899
5. CBLB controls proximal C-type lectin receptor signaling in macrophages and dendritic cells. CBLB associates with SYK and ubiquitinates SYK, dectin-1, and dectin-2 after fungal recognition. CBLB deficiency results in increased inflammasome activation, enhanced reactive oxygen species production, and increased fungal killing. PMID: 27428901
6. study indicates that Cbl-b negatively regulates CLR-mediated antifungal innate immunity PMID: 27432944
7. Fasudil, a clinically safe ROCK inhibitor, decreases disease burden in a Cbl/Cbl-b deficiency-driven murine model of myeloproliferative disorders. PMID: 26177294
8. Mechanistically, NFATc1 induces Nur77 expression at late stage of osteoclast differentiation; in turn, Nur77 transcriptionally up-regulates E3 ubiquitin ligase Cbl-b, which triggers NFATc1 protein degradation. PMID: 26173181
9. Silencing Cbl-b significantly enhanced T lymphocyte function and T lymphocyte cytotoxicity activity PMID: 25249301
10. mechanisms have therapeutic implications for reducing beta-cell proliferation in insulinomas by inhibiting phospho-HLXB9 or its interaction with Nono and modulating the expression of its direct (Cblb) or indirect (c-Met) targets PMID: 26342078
11. SHP-1 regulates Cbl-b-mediated T cell responses by controlling its tyrosine phosphorylation and ubiquitination PMID: 26416283
12. Cbl-b(-/-) T cells demonstrate significant lymph node trafficking abnormalities. PMID: 25829233
13. These results indicated that NF-kappaB downregulated Cbl-b by binding and suppressing Cbl-b promoter in T cell activation PMID: 25762784
14. Cbl-b, together with Stub1, ubiquitinate Foxp3, and regulate tTreg development. PMID: 25560411
15. Whereas Cbl-PI3K interaction regulates differentiation and survival, bone resorption is predominantly regulated by Cbl-b in osteoclasts. PMID: 24470255
16. Cbl-b is the E3 ubiquitin ligase for Stat6. Cbl-b regulates Th9 in both Stat6-dependent and -independent mechanisms. PMID: 24508458
17. The results demonstrate an essential and non-redundant role for Cbl-b in controlling TGFbetaR signaling by directly targeting SMAD7 for degradation during T cell responses in vitro and in vivo. PMID: 23709694
18. Cbl-b, by promoting the ubiquitination and degradation of DDR2, functions as a negative regulator in the DDR2 signaling pathway. PMID: 24631539
19. genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage lymphoma-b) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumours PMID: 24553136
20. Cbl-b plays only a limited role in the induction of antigen-specific T cell responses by murine bone marrow-derived dendritic cells in vitro and in vivo. PMID: 23762309
21. study demonstrates that Cbl-b regulates the fate of inducible regulatory T cells via controlling the threshold for T cell activation PMID: 23749633
22. Cbl-b inhibits T cell activation by suppressing Pten inactivation independently of its ubiquitin ligase activity. PMID: 22763434
23. Data suggest that targeting Cbl-b might serve as a novel 'adjuvant approach', suitable to augment the effectiveness of established anti-cancer immunotherapies. PMID: 21383769
24. c-Cbl as well as Cbl-b may play important roles in Hsp90 inhibitor-induced degradation of Flt3-ITD through the ubiquitin proteasome system PMID: 21768087
25. Cbl-b is a critical factor in maintaining lung homeostasis upon environmental exposure to aeroallergens. PMID: 20738317
26. Interplay between Cblb-dependent T cell anergy and other mechanisms prevents organ-specific islet-cell autoimmunity in transgenic mice. PMID: 21248249
27. Selective genetic inactivation of Cbl-b E3 ligase activity phenocopies the T cell responses observed when total Cbl-b is ablated, resulting in T cell hyperactivation, spontaneous autoimmunity, and impaired induction of T cell anergy in vivo. PMID: 21248250
28. The resilts of this study suggested that Cbl-b is an important regulatory factor for cytotoxic T-cell infiltration via RANTES production in macrophages. PMID: 21254087
29. show that, in contrast to Cbl or Cbl-b single-deficient mice, concurrent loss of Cbl and Cbl-b in the HSC compartment leads to an early-onset lethal myeloproliferative disease in mice PMID: 20805496
30. Data show that intrinsic regulation of peripheral T cells by CBL-B serves a uniquely critical role as a failsafe against clinical onset of autoimmune disease in AIRE deficiency. PMID: 20668237
31. Data suggest that the regulatory abnormalities in Cbl-b(-/-) mice are related to defects in Teff, not Treg, function. PMID: 20624942
32. gene deletion of both Cbl-b and Itch leads to augmented T cell activation and spontaneous autoimmunity PMID: 20637659
33. Results indicate that Cbl-b controls Runx2 expression at the post-translational level. PMID: 20578243
34. This study reveals that Foxo factors promote transcription of the Foxp3 gene in induced T reg cells, and thus provides new mechanistic insight into Foxo-mediated T cell regulation. PMID: 20439537
35. Cbl-b plays a positive modulatory role in GPVI-dependent platelet signaling, which translates to an important regulatory role in hemostasis and thrombosis in vivo PMID: 20400514
36. Cbl-b and itch are key regulators of peripheral T-cell tolerance [review] PMID: 20395198
37. NFATc1 interacts endogenously with c-Src, c-Cbl, and Cbl-b in osteoclasts. PMID: 20037154
38. novel E3 ubiquitin-protein ligase; role in regulation of immune response - review PMID: 11826757
39. Cbl-b negatively regulates BCR signaling by targeting Syk for ubiquitination. PMID: 12771181
40. both c-Cbl and Cbl-b can initiate a phosphatidylinositol 3-kinase/protein kinase B-independent signaling pathway critical to insulin-stimulated GLUT4 translocation PMID: 12842890
41. Cbl-b and c-Cbl have divergent effects on Fc epsilon RI signal transduction and that Cbl-b, but not c-Cbl, functions as a negative regulator of Fc epsilon RI-induced degranulation. PMID: 15265912
42. activated KIT in turn induces phosphorylation and activation of Cbl proteins PMID: 15315962
43. Study provides a molecular framework for Cbl-b/Vav1-dependent and Cbl-b/Vav1-independent CD28 activation pathways essential for the organization of secondary lymphoid tissues and in vivo immunity to viral infection. PMID: 15661906
44. E3 ubiquitin ligase Cbl-b plays an integral role in T cell TGF-beta signaling; its absence results in multifunctional TGF-beta-related defects that have important disease-related implications. PMID: 16424156
45. cbl-b is a negative regulator of long-term memory, and its neuronal mechanism regulates synaptic transmission in the hippocampus PMID: 16549761
46. results suggest that Cbl-b induces resistance of osteoblasts to IGF-I during denervation by increasing IRS-1 degradation and that Cbl-b-mediated modification of IGF-I signaling may contribute to decreased bone formation during denervation PMID: 16734387
47. Cbl proteins play a critical role in establishing the MHC-dependent CD4(+) and CD8(+) T cell development programs. PMID: 17045823
48. Cbl-b functions as a potent negative regulator of cytokines that promote allergic and inflammatory reactions. PMID: 17056522
49. Ablation of Cbl-b can be an efficient strategy for eliciting immune responses against both inoculated and spontaneous tumors. PMID: 17364027
50. identify Cbl-b as a key signaling molecule that controls spontaneous antitumor activity of cytotoxic T cells in different cancer models PMID: 17403934

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KEGG: mmu:208650

STRING: 10090.ENSMUSP00000110115

UniGene: Mm.328206