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

1. Cbls were highly expressed in GC light zone (LZ) B cells, where they promoted the ubiquitination and degradation of Irf4, a transcription factor facilitating PC fate choice. PMID: 29562201
2. Cbl, Cbl-b, and Cbl-c have a role in protecting mammary epithelial cellsfrom proteotoxic stress-induced cell death by promoting turnover of active c-Src PMID: 27930322
3. 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
4. These findings highlight a hitherto unexplored and novel role for Cbl and PI3K in modulating the osteogenic response of periosteal cells during the early stages of fracture repair. PMID: 27884787
5. c-Cbl negatively regulates IFN-beta signaling and cellular antiviral response by promoting IRF3 ubiquitination and degradation. PMID: 27503123
6. This study demonstrate an unprecedented role for c-Cbl in microglia-mediated neuroinflammation involving PI3K/Akt/NF-kappaB pathway. PMID: 27156691
7. c-Cbl's linker helix region mutations are only oncogenic when they disrupt the native state and fail to ubiquitinate protein tyrosine kinases. PMID: 27609087
8. 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
9. mutant CBL proteins effectively compete with the remaining wild type CBL-B and juxtapose tyrosine kinase-binding domain-associated protein tyrosine kinases with proline-rich region-associated signaling proteins to hyper-activate signaling downstream of hematopoietic growth factor receptors PMID: 28082680
10. results demonstrate that c-Cbl mediates the ubiquitination/degradation of integrin beta1, which leads to COMP deficiency-induced dilated cardiomyopathy. PMID: 27693578
11. Gem, a gene encoding a GTPase that is upregulated by Cbl(Q367P) , enhanced hematopoietic stem cell activity and induced myeloid cell proliferation. In addition, Evi1, a gene encoding a transcription factor, was found to cooperate with Cbl(Q367P) and progress CMML to AML. PMID: 28209720
12. Fasudil, a clinically safe ROCK inhibitor, decreases disease burden in a Cbl/Cbl-b deficiency-driven murine model of myeloproliferative disorders. PMID: 26177294
13. Cbl down-regulation protects mice against high-fat diet-induced obesity and insulin resistance. PMID: 26296084
14. Cbl-b and c-Cbl regulate the degradation of Osterix through the ubiquitin-proteasome pathway. PMID: 25744063
15. Overexpression of Smad7 in human HaCaT keratinocyte cells and mouse skin tissues elevated EGF receptor (EGFR) activity by impairing ligand-induced ubiquitination and degradation of activated receptor, which is induced by the E3 ubiquitin ligase c-Cbl. PMID: 26055326
16. Erbin promotes tumourigenesis and tumour growth in colorectal cancer by stabilizing epidermal growth factor receptor PMID: 25521828
17. Whereas Cbl-PI3K interaction regulates differentiation and survival, bone resorption is predominantly regulated by Cbl-b in osteoclasts. PMID: 24470255
18. c-Cbl activation promotes myocyte apoptosis, inhibits angiogenesis, and causes adverse cardiac remodeling after myocardial infarction. PMID: 24583314
19. Data indicate a Cbl/p85/epsin-1 pathway in erythropoietin receptor (EpoR) endocytosis. PMID: 24113870
20. These results support the notion that the distal cytoplasmic domain of CD5, including Y463, plays a relevant role in the downmodulation of TCR signals in thymocytes via c-Cbl. PMID: 23376399
21. c-Cbl conjugates neural precursor cell-expressed, developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, to TbetaRII at Lys556 and Lys567. PMID: 23290524
22. the novel role for Syk signaling and the Syk-binding ubiquitin ligase c-Cbl in the BCR-mediated processing and presentation of cognate antigen and PMID: 22451666
23. Casitas b-lineage lymphoma (c-Cbl) is involved in focal adhesion and myofibrillar protein stability and turnover in myocytes PMID: 22203672
24. c-Cbl has a crucial, RING-domain-dependent role in regulating dendritic cell maturation, probably by facilitating the regulatory function of p105 and/or p50. PMID: 21799517
25. Results indicate that c-Cbl and particularly its phosphorylated residue Y731 plays an important role in platelet outside-in signaling contributing to platelet-spreading and clot retraction. PMID: 21967979
26. 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
27. Cbl inactivation reverses the deficiency of T cell development in Vav1 knockout mice PMID: 21490975
28. identify a surprising but pivotal role for dynein and the microtubule network alongside Grb2, Dok-3, and Cbl in antigen gathering during B cell activation PMID: 21703542
29. propose c-Cbl as an angiogenic suppressor protein where upon activation it uniquely modulates PLCgamma1 activation by ubiquitination and subsequently inhibits VEGF-driven angiogenesis PMID: 21242968
30. Data show that degradation of BCR-ABL by As4S4 was mediated by c-CBL, a RING-type E3 ligase that was also shown to be involved in ubiquitination for many other receptor/protein tyrosine kinases. PMID: 21118980
31. loss of Cbl-phosphatidylinositol 3-kinase interaction perturbs RANKL-mediated signaling, inhibiting bone resorption and promoting osteoclast survival. PMID: 20851882
32. Mice with a mutation in the RING finger domain of c-Cbl show that E3 ubiquitin ligase activity of c-Cbl is required to restrict myeloid leukemia development. PMID: 20951944
33. 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
34. document that a deficiency of the E3 ubiquitin ligase c-Cbl in lymphocytes results in an age-dependent lymphopenia. PMID: 20404156
35. Abrogation of the Cbl-PI3K interaction, although not affecting M-CSF-induced proliferation and differentiation of precursors, is required for regulation of survival and actin cytoskeletal reorganization of mature osteoclasts. PMID: 20392263
36. Data show that that the increased Notch3-IC degradation correlates with higher levels of c-Cbl tyrosine phosphorylation in Notch3-IC/pTalpha(-/-) double-mutant thymocytes. PMID: 19966856
37. Cbl-b (and c-Cbl) accumulation at the anergic synapse may play an important role in anergy maintenance, induction, or both. PMID: 20207996
38. a BCR-ABL mutant lacking direct binding sites for the GRB2, CBL and CRKL adapter proteins fails to induce leukemia in mice PMID: 19823681
39. NFATc1 interacts endogenously with c-Src, c-Cbl, and Cbl-b in osteoclasts. PMID: 20037154
40. Data indicate that Fyn was not required for the induction of central tolerance by negative selection, the adaptor protein role of c-Cbl, or the normal development and function of Treg. PMID: 19904769
41. transmembrane form of Notch1 was tyrosine-phosphorylated and specifically coprecipitated with the ubiquitin ligase c-Cbl PMID: 11777909
42. Cbl-b knockout mice are available. Negative regulation of immune responses by three new E3 ubiquitin-protein ligases, Cbl, Cbl-b, & Itch is mediated by TCR, PI3-K, Notch and Lck. PMID: 11826757
43. APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes PMID: 11997497
44. Isolation and characterization of a novel, transforming allele of the c-Cbl proto-oncogene from a murine macrophage cell line. PMID: 12032836
45. EGF-inducible direct association of PLC-gamma1 with c-Cbl in vivo that is mediated by the SH3 domain of PLC-gamma1. PMID: 12061819
46. Cbl-b protein and CIN85 downregulate receptor tyrosine kinases PMID: 12177062
47. c-Cbl is a negative regulator of GH-stimulated STAT5-mediated transcription by direction of STAT5 for proteosomal degradation PMID: 12193575
48. Both PMA-treated wild type and hck(-/-)fgr(-/-) macrophages were defective in spontaneous and chemotactic migration and tyrosine phosphorylation of the Cbl protooncoprotein was decreased in both. PMID: 12652654
49. Loss of c-Cbl expression leads to an increase in dual TCR alpha chain expression on the surface of double positive thymocytes, suggesting that regulation of TCR degradation via ubiquitination is key in phenotypic allelic exclusion. PMID: 12707333
50. findings establish Cbl protein as the major endogenous ubiquitin ligase responsible for epidermal growth factor receptor degradation PMID: 12754251

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KEGG: mmu:12402

STRING: 10090.ENSMUSP00000041902

UniGene: Mm.266871