Gene Symbol: CBLB
Description: Cbl proto-oncogene B
Alias: Cbl-b, Nbla00127, RNF56, E3 ubiquitin-protein ligase CBL-B, Cas-Br-M (murine) ecotropic retroviral transforming sequence b, Cbl proto-oncogene B, E3 ubiquitin protein ligase, Cbl proto-oncogene, E3 ubiquitin protein ligase B, RING finger protein 56, RING-type E3 ubiquitin transferase CBL-B, SH3-binding protein CBL-B, casitas B-lineage lymphoma proto-oncogene b, signal transduction protein CBL-B
Species: human
Products:     CBLB

Top Publications

  1. Flanders J, Feng Q, Bagrodia S, Laux M, Singavarapu A, Cerione R. The Cbl proteins are binding partners for the Cool/Pix family of p21-activated kinase-binding proteins. FEBS Lett. 2003;550:119-23 pubmed
  2. Bustelo X, Crespo P, López Barahona M, Gutkind J, Barbacid M. Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation. Oncogene. 1997;15:2511-20 pubmed
  3. Kobashigawa Y, Tomitaka A, Kumeta H, Noda N, Yamaguchi M, Inagaki F. Autoinhibition and phosphorylation-induced activation mechanisms of human cancer and autoimmune disease-related E3 protein Cbl-b. Proc Natl Acad Sci U S A. 2011;108:20579-84 pubmed publisher
  4. Keane M, Rivero Lezcano O, Mitchell J, Robbins K, Lipkowitz S. Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene. Oncogene. 1995;10:2367-77 pubmed
    ..Together, cbl-b and c-cbl are members of a novel family of proto-oncogenes involved in signal transduction. ..
  5. Lavagna Sévenier C, Marchetto S, Birnbaum D, Rosnet O. The CBL-related protein CBLB participates in FLT3 and interleukin-7 receptor signal transduction in pro-B cells. J Biol Chem. 1998;273:14962-7 pubmed
    ..We have found that CBLB, a recently characterized molecule closely related to the CBL protooncogene product, is phosphorylated on tyrosine(..
  6. Elly C, Witte S, Zhang Z, Rosnet O, Lipkowitz S, Altman A, et al. Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation. Oncogene. 1999;18:1147-56 pubmed
    ..The Crk-L-binding sites were further determined to be Y655DVP and Y709KIP, with the latter being the primary binding site. Taken together, these results implicate that Cbl-b is involved in TCR-mediated intracellular signaling pathways. ..
  7. Zhang Z, Elly C, Qiu L, Altman A, Liu Y. A direct interaction between the adaptor protein Cbl-b and the kinase zap-70 induces a positive signal in T cells. Curr Biol. 1999;9:203-6 pubmed
    ..Unlike the proposed role of Cbl as a negative regulator, our results suggest that the Cbl homologue Cbl-b has a positive role in T-cell signaling, most likely via a direct interaction with the upstream kinase Zap-70. ..
  8. Ettenberg S, Keane M, Nau M, Frankel M, Wang L, Pierce J, et al. cbl-b inhibits epidermal growth factor receptor signaling. Oncogene. 1999;18:1855-66 pubmed
    ..These data demonstrate that cbl-b inhibits EGF-induced cell growth and that cbl-b and c-cbl have distinct roles in EGF mediated signaling. ..
  9. Levkowitz G, Waterman H, Ettenberg S, Katz M, Tsygankov A, Alroy I, et al. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol Cell. 1999;4:1029-40 pubmed
    ..Our study identifies Cbl proteins as components of the ubiquitin ligation machinery and implies that they similarly suppress many other signaling pathways. ..

More Information

Publications150 found, 100 shown here

  1. Ettenberg S, Magnifico A, Cuello M, Nau M, Rubinstein Y, Yarden Y, et al. Cbl-b-dependent coordinated degradation of the epidermal growth factor receptor signaling complex. J Biol Chem. 2001;276:27677-84 pubmed
    ..Furthermore, the data demonstrate that Cbl-b mediates degradation of multiple proteins in the EGFR-signaling complex. ..
  2. Kim M, Tezuka T, Tanaka K, Yamamoto T. Cbl-c suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation. Oncogene. 2004;23:1645-55 pubmed
    ..Therefore, activated Src may be a direct target of Cbl-c in vivo. Our results suggest that Cbl and Cbl-b suppress v-Src-induced transformation through mechanisms distinct from that of Cbl-c. ..
  3. Schulze W, Deng L, Mann M. Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol Syst Biol. 2005;1:2005.0008 pubmed
    ..Our results demonstrate that system-wide mapping of peptide-protein interactions sites is possible, and suggest shared and unique roles of ErbB-receptor family members in downstream signaling. ..
  4. Oshikawa G, Nagao T, Wu N, Kurosu T, Miura O. c-Cbl and Cbl-b ligases mediate 17-allylaminodemethoxygeldanamycin-induced degradation of autophosphorylated Flt3 kinase with internal tandem duplication through the ubiquitin proteasome pathway. J Biol Chem. 2011;286:30263-73 pubmed publisher
  5. Fang D, Wang H, Fang N, Altman Y, Elly C, Liu Y. Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. J Biol Chem. 2001;276:4872-8 pubmed
    ..The data suggest a molecular link for Cbl-b-mediated negative regulation of Vav, with phosphatidylinositol 3-kinase as a direct target for Cbl-b E3 ubiquitin ligase. ..
  6. Arron J, Vologodskaia M, Wong B, Naramura M, Kim N, Gu H, et al. A positive regulatory role for Cbl family proteins in tumor necrosis factor-related activation-induced cytokine (trance) and CD40L-mediated Akt activation. J Biol Chem. 2001;276:30011-7 pubmed
    ..These findings implicate Cbl family proteins as not only negative regulators of signaling but as positive modulators of TNF receptor superfamily signaling as well. ..
  7. Fang D, Liu Y. Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells. Nat Immunol. 2001;2:870-5 pubmed
    ..The enhanced activation of Cbl-b(-/-) T cells was suppressed by the inhibition of PI3K. The results suggest a proteolysis-independent function for Cbl-b in the modification of protein recruitment. ..
  8. Yasuda T, Tezuka T, Maeda A, Inazu T, Yamanashi Y, Gu H, et al. Cbl-b positively regulates Btk-mediated activation of phospholipase C-gamma2 in B cells. J Exp Med. 2002;196:51-63 pubmed
    ..These results demonstrate that Cbl-b positively regulates BCR-mediated Ca2+ signaling, most likely by influencing the Btk/BLNK/PLC-gamma2 complex formation. ..
  9. Zeng S, Xu Z, Lipkowitz S, Longley J. Regulation of stem cell factor receptor signaling by Cbl family proteins (Cbl-b/c-Cbl). Blood. 2005;105:226-32 pubmed
    ..The activated KIT in turn induces phosphorylation and activation of Cbl proteins. The Cbl proteins then bind and direct the degradation of activated KIT, leading to down-regulation of KIT signaling. ..
  10. Peer S, Baier G, Gruber T. Cblb-deficient T cells are less susceptible to PD-L1-mediated inhibition. Oncotarget. 2017;8:41841-41853 pubmed publisher
    ..Furthermore, it has been shown that Cblb deficiency enhances T cell effector functions towards tumors...
  11. Baker E, Sloan J, Hauser N, Gropman A, Adams D, Toro C, et al. MRI characteristics of globus pallidus infarcts in isolated methylmalonic acidemia. AJNR Am J Neuroradiol. 2015;36:194-201 pubmed publisher
    ..Globus pallidus infarct prevalence by methylmalonic acidemia class was the following: cblA (5/7, 71%), cblB (3/7, 43%), mut(o) (10/22, 45%), and mut- (1/4, 25%)...
  12. Richard E, Brasil S, Briso Montiano Á, Alonso Barroso E, Gallardo M, Merinero B, et al. Generation and characterization of two human iPSC lines from patients with methylmalonic acidemia cblB type. Stem Cell Res. 2018;29:143-147 pubmed publisher
    ..pluripotent stem cell (iPSC) lines were generated from fibroblasts of two siblings with methylmalonic acidemia cblB type carrying mutations in the MMAB gene: c.287T➔C (p.Ile96Thr) and a splicing loss-of-function variant c...
  13. Kowanetz K, Szymkiewicz I, Haglund K, Kowanetz M, Husnjak K, Taylor J, et al. Identification of a novel proline-arginine motif involved in CIN85-dependent clustering of Cbl and down-regulation of epidermal growth factor receptors. J Biol Chem. 2003;278:39735-46 pubmed
    ..Thus, specific interactions of CIN85 SH3 domains with the PXXXPR motif in Cbl play multiple roles in down-regulation of receptor tyrosine kinases. ..
  14. Hinrichs C. Molecular Pathways: Breaking the Epithelial Cancer Barrier for Chimeric Antigen Receptor and T-cell Receptor Gene Therapy. Clin Cancer Res. 2016;22:1559-64 pubmed publisher
    ..Other work is delineating whether control of genes for immune checkpoint receptors (e.g.,PDCD1, CTLA4) and cytokine and TCR signaling regulators (e.g.,CBLB, CISH, IL12, IL15) can increase the antitumor activity of therapeutic T cells.
  15. Jack J, Small G, Brown C, Havener T, McLeod H, Motsinger Reif A, et al. Gene expression and linkage analysis implicate CBLB as a mediator of rituximab resistance. Pharmacogenomics J. 2017;: pubmed publisher
    ..We discovered novel loci with genome-wide mapping analyses and functionally validated one of these genes, CBLB, which causes rituximab resistance when knocked down in lymphoma cells...
  16. Martinelli S, Stellacci E, Pannone L, D Agostino D, Consoli F, Lissewski C, et al. Molecular Diversity and Associated Phenotypic Spectrum of Germline CBL Mutations. Hum Mutat. 2015;36:787-96 pubmed publisher
    ..Finally, we excluded a major contribution of two additional members of the CBL family, CBLB and CBLC, to NS and related disorders.
  17. Zhang G, Liu J, Zhang Y, Qu J, Xu L, Zheng H, et al. Cbl-b-dependent degradation of FLIP(L) is involved in ATO-induced autophagy in leukemic K562 and gastric cancer cells. FEBS Lett. 2012;586:3104-10 pubmed publisher
    ..Our findings lead to a better understanding of the mechanism of action of ATO, and suggest that a novel signaling pathway is required for ATO-induced autophagy in K562 and MGC803 cells. ..
  18. Kwak S, Kim B, Ahn H, Yoo J, Kim J, Bae I, et al. Ionizing radiation-inducible miR-30e promotes glioma cell invasion through EGFR stabilization by directly targeting CBL-B. FEBS J. 2015;282:1512-25 pubmed publisher
    ..Collectively, our results suggest that targeting miR-30e may limit the invasiveness induced during glioma radiotherapy. ..
  19. Desai S, Kharade S, Parekh V, Iyer S, Agarwal S. Pro-oncogenic Roles of HLXB9 Protein in Insulinoma Cells through Interaction with Nono Protein and Down-regulation of the c-Met Inhibitor Cblb (Casitas B-lineage Lymphoma b). J Biol Chem. 2015;290:25595-608 pubmed publisher
    ..chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) identified the c-Met inhibitor, Cblb, as a direct phospho-HLXB9 target gene...
  20. Keyfi F, Abbaszadegan M, Sankian M, Rolfs A, Orolicki S, Pournasrollah M, et al. Mutation analysis of genes related to methylmalonic acidemia: identification of eight novel mutations. Mol Biol Rep. 2019;46:271-285 pubmed publisher
    ..Using clinical, biochemical, structural and molecular analyses we identified 15 mut MMA, three cblA, one cblB, and four cblC-deficient patients. Among mutations identified in the MUT gene (MUT) only one, the c.1874A>C (p...
  21. Okabe S, Tauchi T, Ohyashiki K, Broxmeyer H. Stromal-cell-derived factor-1/CXCL12-induced chemotaxis of a T cell line involves intracellular signaling through Cbl and Cbl-b and their regulation by Src kinases and CD45. Blood Cells Mol Dis. 2006;36:308-14 pubmed
    ..Our results implicate CD45, Cbl, Cbl-b, src kinases and potentially other associated proteins as mediators of SDF-1alpha/CXCL12-induced cell migration of Jurkat T cells. ..
  22. Sproul A, Xu Z, Wilhelm M, Gire S, Greene L. Cbl negatively regulates JNK activation and cell death. Cell Res. 2009;19:950-61 pubmed publisher
    ..Apoptotic stimuli lead to loss of Cbl protein/activity, thereby removing a critical brake on JNK activation and on cell death. ..
  23. Teh C, Daley S, Enders A, Goodnow C. T-cell regulation by casitas B-lineage lymphoma (Cblb) is a critical failsafe against autoimmune disease due to autoimmune regulator (Aire) deficiency. Proc Natl Acad Sci U S A. 2010;107:14709-14 pubmed publisher
    ..tolerance mechanisms: activation-induced cell death (Fasl(gld/gld)), anergy and requirement for CD28 costimulation (Cblb(-/-)), inhibition of ICOS and T(FH) cells (Rc3h1(san/san)), or decreased numbers of Foxp3(+) T regulatory cells (..
  24. Hong F, Huang X, Zhang Y, Yang J, Tong F, Mao H, et al. [Screening for newborn organic aciduria in Zhejiang province:prevalence, outcome and follow-up]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2017;46:240-247 pubmed
    ..5%) were combined type. Genetic analysis showed 6 cases of MUT type and 1 case of CblB type out of 7 patients with MMA simple type, 10 cases of CblC and 1 case of CblF out of 11 patients with combined ..
  25. Bachmaier K, Toya S, Gao X, Triantafillou T, Garrean S, Park G, et al. E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury. Nat Med. 2007;13:920-6 pubmed
    The E3 ubiquitin ligase Cblb has a crucial role in the prevention of chronic inflammation and autoimmunity. Here we show that Cblb also has an unexpected function in acute lung inflammation...
  26. Voisinne G, García Blesa A, Chaoui K, Fiore F, Bergot E, Girard L, et al. Co-recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies CD5 as a key regulator of TCR-induced ubiquitylation. Mol Syst Biol. 2016;12:876 pubmed publisher
    ..is essential for the function of T cells and negatively regulated by the E3 ubiquitin-protein ligases CBL and CBLB Here, we combined mouse genetics and affinity purification coupled to quantitative mass spectrometry to monitor the ..
  27. Nanjappa S, Mudalagiriyappa S, Fites J, Suresh M, Klein B. CBLB Constrains Inactivated Vaccine-Induced CD8+ T Cell Responses and Immunity against Lethal Fungal Pneumonia. J Immunol. 2018;201:1717-1726 pubmed publisher
    ..In this study, we show that CBLB, a negative regulator of TCR signaling, suppresses CD8+ T cells in response to inactivated fungal ..
  28. Kumar S, Naqvi R, Khanna N, Rao D. Disruption of HLA-DR raft, deregulations of Lck-ZAP-70-Cbl-b cross-talk and miR181a towards T cell hyporesponsiveness in leprosy. Mol Immunol. 2011;48:1178-90 pubmed publisher
    ..Thus, this study for the first time pinpointed overexpression of Cbl-b and expressional losses of miR-181 as important hallmarks of progression of leprosy. ..
  29. Hinterleitner R, Gruber T, Pfeifhofer Obermair C, Lutz Nicoladoni C, Tzankov A, Schuster M, et al. Adoptive transfer of siRNA Cblb-silenced CD8+ T lymphocytes augments tumor vaccine efficacy in a B16 melanoma model. PLoS ONE. 2012;7:e44295 pubmed publisher
    ..We recently showed that adoptive cell transfer (ACT) of cblb(-/-) CD8(+) T cells enhances dendritic cell (DC) immunization-mediated anti-tumor effects in immune-competent ..
  30. Wallner S, Lutz Nicoladoni C, Tripp C, Gastl G, Baier G, Penninger J, et al. The role of the e3 ligase cbl-B in murine dendritic cells. PLoS ONE. 2013;8:e65178 pubmed publisher
    ..e. Cbl-b) is highly expressed in murine bone-marrow-derived DCs (BMDCs). Differentiation of cblb-/- bone marrow mononuclear cells into classical BMDCs is unaltered, except enhanced induction of DEC-205 (CD205) ..
  31. Liu Y, Wang H, Wu T, Li X, Song J, DING Y, et al. [A Chinese boy with methylmalonic aciduria cblB type and a novel mutation in the MMAB gene]. Zhongguo Dang Dai Er Ke Za Zhi. 2015;17:172-5 pubmed
    b>cblB defect is a rare type of methylmalonic aciduria. In this study, a Chinese boy was diagnosed with methylmalonic aciduria cblB type and a novel mutation in the MMAB gene...
  32. Ishaque N, Abba M, Hauser C, Patil N, Paramasivam N, Huebschmann D, et al. Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer. Nat Commun. 2018;9:4782 pubmed publisher
    ..3, AC010091, SNHG14, 3' UTRs of FOXP2, DACH2, TRPM3, XKR4, ANO5, CBL, CBLB, the latter four potentially dual protagonists in metastasis and efferocytosis-/PD-L1 mediated immunosuppression...
  33. Perez B, Angaroni C, Sánchez Alcudia R, Merinero B, Perez Cerda C, Specola N, et al. The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America. J Inherit Metab Dis. 2010;33:S307-14 pubmed publisher
    ..271dupA mutation. All mut(0), cblB and cblC patients presented the symptoms early and in general had more neurological complications, while cblA and ..
  34. Chen D, Si W, Shen J, Du C, Lou W, Bao C, et al. miR-27b-3p inhibits proliferation and potentially reverses multi-chemoresistance by targeting CBLB/GRB2 in breast cancer cells. Cell Death Dis. 2018;9:188 pubmed publisher
    ..Mechanistic analysis indicated that miR-27b enhanced responses to PTX by directly targeting CBLB and GRB2 to inactivate both PI3K/Akt and MAPK/Erk signaling pathways...
  35. Li P, Wang X, Liu Z, Liu H, Xu T, Wang H, et al. Single Nucleotide Polymorphisms in CBLB, a Regulator of T-Cell Response, Predict Radiation Pneumonitis and Outcomes After Definitive Radiotherapy for Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2016;17:253-262.e5 pubmed publisher
    ..at a single institution between March 1998 and February 2009 were used to genotype 3 potentially functional SNPs in CBLB (rs1042852 C>T, rs2305035 G>A, and rs7649466 C>G)...
  36. Alcázar I, Cortes I, Zaballos A, Hernandez C, Fruman D, Barber D, et al. p85beta phosphoinositide 3-kinase regulates CD28 coreceptor function. Blood. 2009;113:3198-208 pubmed publisher
  37. Mc Guire P, Parikh A, Diaz G. Profiling of oxidative stress in patients with inborn errors of metabolism. Mol Genet Metab. 2009;98:173-80 pubmed publisher
    ..Of note, patients with cobalamin disorders (i.e., CblB and CblC) consistently had the highest levels of oxidative damage markers...
  38. Wong E, Lim J, Low B, Chen Q, Guy G. Evidence for direct interaction between Sprouty and Cbl. J Biol Chem. 2001;276:5866-75 pubmed
    ..Our results suggest that one function of hSPRY2 in signaling processes downstream of RTKs may be to modulate c-Cbl physiological function such as that seen with receptor-mediated endocytosis. ..
  39. Kurakin A, Wu S, Bredesen D. Atypical recognition consensus of CIN85/SETA/Ruk SH3 domains revealed by target-assisted iterative screening. J Biol Chem. 2003;278:34102-9 pubmed
    ..A direct interaction of synaptojanin 1 and PAK2 with CIN85 SH3 domains was confirmed by Far Western blotting. ..
  40. Watanabe Y, Sasahara Y, Ramesh N, Massaad M, Yeng Looi C, Kumaki S, et al. T-cell receptor ligation causes Wiskott-Aldrich syndrome protein degradation and F-actin assembly downregulation. J Allergy Clin Immunol. 2013;132:648-655.e1 pubmed publisher
    ..WASP degradation might provide a mechanism for regulating WASP-dependent TCR-driven assembly of F-actin. ..
  41. Dong Q, Li C, Che X, Qu J, Fan Y, Li X, et al. MicroRNA-891b is an independent prognostic factor of pancreatic cancer by targeting Cbl-b to suppress the growth of pancreatic cancer cells. Oncotarget. 2016;7:82338-82353 pubmed publisher
    ..The results provide a theoretical basis for the study of miR-891b as an independent prognostic predictor of PDAC and the role of miR-891b/Cbl-b pathway in this prediction, as well as the identification of new targets for PDAC. ..
  42. Hoyne G, Flening E, Yabas M, Teh C, Altin J, Randall K, et al. Visualizing the role of Cbl-b in control of islet-reactive CD4 T cells and susceptibility to type 1 diabetes. J Immunol. 2011;186:2024-32 pubmed publisher
    ..When removed from regulatory T cells and placed in culture, Cblb-deficient islet-reactive CD4(+) cells reveal a capacity to proliferate to HEL Ag that is repressed in wild-type ..
  43. Lutz Nicoladoni C, Wallner S, Stoitzner P, Pircher M, Gruber T, Wolf A, et al. Reinforcement of cancer immunotherapy by adoptive transfer of cblb-deficient CD8+ T cells combined with a DC vaccine. Immunol Cell Biol. 2012;90:130-4 pubmed publisher
    ..b>cblb-deficient animals reject tumors via CD8(+) T cells, which make Cbl-b an ideal target for improvement of adoptive T-..
  44. Koba H, Kimura H, Nishikawa S, Sone T, Abo M, Hara J, et al. Next-generation sequencing analysis identifies genomic alterations in pathological morphologies: A case of pulmonary carcinosarcoma harboring EGFR mutations. Lung Cancer. 2018;122:146-150 pubmed publisher
    ..Intriguingly, identification of genomic alterations with NGS found five identical alterations in four genes (EGFR, CBLB, TP53, and MEN1) that were shared by the two components, and that each component had a large number of individual ..
  45. Rochman Y, Yukawa M, Kartashov A, Barski A. Functional characterization of human T cell hyporesponsiveness induced by CTLA4-Ig. PLoS ONE. 2015;10:e0122198 pubmed publisher
    ..unlike some models of T cell anergy, these cells did not possess increased levels of the TCR signaling inhibitor CBLB. Rather, the CTLA4-Ig-induced hyporesponsiveness was associated with an elevated level of p27kip1 cyclin-dependent ..
  46. Zhang L, Teng Y, Fan Y, Wang Y, Li W, Shi J, et al. The E3 ubiquitin ligase Cbl-b improves the prognosis of RANK positive breast cancer patients by inhibiting RANKL-induced cell migration and metastasis. Oncotarget. 2015;6:22918-33 pubmed
    ..Our results suggest that Cbl-b improves the prognosis of RANK-expressing breast cancer patients by inhibiting RANKL-induced breast cancer cell migration and metastasis. ..
  47. Jahan A, Lestra M, Swee L, Fan Y, Lamers M, Tafesse F, et al. Usp12 stabilizes the T-cell receptor complex at the cell surface during signaling. Proc Natl Acad Sci U S A. 2016;113:E705-14 pubmed publisher
    ..Our approach benefits from the use of activity-based probes in primary cells without any previous genome modification, and underscores the importance of ubiquitin-mediated regulation to refine signaling cascades. ..
  48. Prasad A, Rabionet R, Espinet B, Zapata L, Puiggros A, Melero C, et al. Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome. J Invest Dermatol. 2016;136:1490-1499 pubmed publisher
    ..the T-cell receptor signaling pathway and tumorigenesis were disrupted in Sézary syndrome patients, for example, CBLB, RASA2, BCL7C, RAMP3, TBRG4, and DAD1...
  49. Yamamoto T, Iwasaki K, Murotani K, Takeda A, Futamura K, Okada M, et al. Peripheral blood immune response-related gene analysis for evaluating the potential risk of chronic antibody-mediated rejection. Hum Immunol. 2018;79:432-438 pubmed publisher
    ..The expression levels of fourteen key molecules (Foxp3, CTLA-4, CCR7, TGF-?, IGLL-1, IL-10, ITCH, CBLB, Bcl-6, CXCR5, granzyme B, CIITA, Baff, TOAG-1/TCAIM) related to regulatory/cytotoxic function of immune cells were ..
  50. Xiao Y, Qiao G, Tang J, Tang R, Guo H, Warwar S, et al. Protein Tyrosine Phosphatase SHP-1 Modulates T Cell Responses by Controlling Cbl-b Degradation. J Immunol. 2015;195:4218-27 pubmed publisher
    ..The aberrant Th2 phenotype observed in T cell-specific Shp1(-/-) mice is reminiscent of heightened Th2 response in Cblb(-/-) mice...
  51. Hörster F, Kölker S, Loeber J, Cornel M, Hoffmann G, Burgard P. Newborn Screening Programmes in Europe, Arguments and Efforts Regarding Harmonisation: Focus on Organic Acidurias. JIMD Rep. 2017;32:105-115 pubmed publisher
    ..I (GA-I) was performed in ten, for isovaleric aciduria (IVA) in nine and for methylmalonic aciduria including cblA, cblB, cblC and cblD (MMACBL) as well as for propionic aciduria (PA) in seven countries...
  52. Ruppert T, Schumann A, Gröne H, Okun J, Kölker S, Morath M, et al. Molecular and biochemical alterations in tubular epithelial cells of patients with isolated methylmalonic aciduria. Hum Mol Genet. 2015;24:7049-59 pubmed publisher
    ..and mut(-) subtype respectively) and by defects in the metabolism of its cofactor 5'-deoxyadenosylcobalamin (cblA, cblB or cblD variant 2 type)...
  53. Payne F, Cooper J, Walker N, Lam A, Smink L, Nutland S, et al. Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes. J Leukoc Biol. 2007;81:581-3 pubmed
    ..Recently, evidence of a statistical interaction between polymorphisms in two negative immunoregulatory genes, CBLB and CTLA4, has been reported in type 1 diabetes (T1D)...
  54. De Schutter J, Guillabert A, Imbault V, Degraef C, Erneux C, Communi D, et al. SHIP2 (SH2 domain-containing inositol phosphatase 2) SH2 domain negatively controls SHIP2 monoubiquitination in response to epidermal growth factor. J Biol Chem. 2009;284:36062-76 pubmed publisher
    ..The present study thus reveals an unexpected and novel role of SHIP2 SH2 domain in the regulation of its newly identified monoubiquitination. ..
  55. Qiao G, Lei M, Li Z, Sun Y, Minto A, Fu Y, et al. Negative regulation of CD40-mediated B cell responses by E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-B. J Immunol. 2007;179:4473-9 pubmed
    ..Together, our data suggest that Cbl-b attenuates CD40-mediated NF-kappaB and JNK activation, thereby suppressing B cell responses. ..
  56. Hsu T, Lin S, Lu P, Chang W, Hung C, Yeh Y, et al. MMP7-mediated cleavage of nucleolin at Asp255 induces MMP9 expression to promote tumor malignancy. Oncogene. 2015;34:826-37 pubmed publisher
    ..TNCL increased the expression of several oncogenes, including MMP9, anaplastic lymphoma kinase (ALK), HIF1a and CBLB, and decreased the expression of tumor suppressors including BRD4, PCM1, TFG and KLF6 by modulating mRNA stability ..
  57. Balachandran P, Dragone L, Garrity Ryan L, Lemus A, Weiss A, Engel J. The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T-mediated virulence. J Clin Invest. 2007;117:419-27 pubmed
    ..To the best of our knowledge, this represents the first identification of a mammalian gene product that is specifically required for in vivo resistance to disease mediated by a type III-secreted effector. ..
  58. Dong Q, Liu Y, Qu X, Hou K, Li L. [Expression of c-Cbl, Cbl-b, and epidermal growth factor receptor in gastric carcinoma and their clinical significance]. Chin J Cancer. 2010;29:59-64 pubmed
    ..Overexpressions of c-Cbl, Cbl-b, and EGFR are closely related to the invasion and progression of gastric carcinoma. c-Cbl and Cbl-b may serve as novel molecular markers for gastric carcinoma. ..
  59. Lin Y, Lin C, Lin W, Zheng Z, Han M, Fu Q. Mild clinical features of isolated methylmalonic acidemia associated with a novel variant in the MMAA gene in two Chinese siblings. BMC Med Genet. 2018;19:114 pubmed publisher
    ..enzymatic subtype, respectively); a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin (cblA, cblB, or cblD-MMA); or deficiency of the enzyme methylmalonyl-CoA epimerase. The cblA type of MMA is very rare in China...
  60. Cao Y, Qu J, Li C, Yang D, Hou K, Zheng H, et al. Celecoxib sensitizes gastric cancer to rapamycin via inhibition of the Cbl-b-regulated PI3K/Akt pathway. Tumour Biol. 2015;36:5607-15 pubmed publisher
    ..Our results suggest that celecoxib-mediated upregulation of Cbl-b is responsible, at least in part, for the additive antitumor effect of celecoxib and rapamycin via inhibition of rapamycin-induced Akt activation. ..
  61. Fujiwara M, Anstadt E, Khanna K, Clark R. Cbl-b-deficient mice express alterations in trafficking-related molecules but retain sensitivity to the multiple sclerosis therapeutic agent, FTY720. Clin Immunol. 2015;158:103-13 pubmed publisher
    ..GWAS have linked CBLB gene polymorphisms with MS and recent evidence demonstrated that these polymorphisms can be associated with ..
  62. Moncalian G, Cárdenes N, Deribe Y, Spínola Amilibia M, Dikic I, Bravo J. Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain. J Biol Chem. 2006;281:38845-53 pubmed
    ..Detailed analyses on the interacting surfaces also provide the basis for a differential Cbl-b molecular recognition of CMS and CIN85. ..
  63. Zhou Z, Gao H, Zhou C, Chang Y, Hong J, Song A, et al. Differential ubiquitin binding of the UBA domains from human c-Cbl and Cbl-b: NMR structural and biochemical insights. Protein Sci. 2008;17:1805-14 pubmed publisher
    ..That is, the amino acid residue diversity in the helix-1 region, but not the dimerization, determines the abilities of various UBA domains binding with Ub. ..
  64. Gómez Martín D, Ibarra Sánchez M, Romo Tena J, Cruz Ruíz J, Esparza Lopez J, Galindo Campos M, et al. Casitas B lineage lymphoma b is a key regulator of peripheral tolerance in systemic lupus erythematosus. Arthritis Rheum. 2013;65:1032-42 pubmed publisher
    ..These findings suggest that abnormal peripheral tolerance in SLE is caused by a deficiency in Cbl-b, and that this ubiquitin ligase plays a key role in regulating TCR signaling during the induction of peripheral tolerance. ..
  65. Shafaat M, Alaee M, Rahmanifar A, Setoodeh A, Razzaghy Azar M, Bagherian H, et al. Autozygosity mapping of methylmalonic acidemia associated genes by short tandem repeat markers facilitates the identification of five novel mutations in an Iranian patient cohort. Metab Brain Dis. 2018;33:1689-1697 pubmed publisher
    ..Other subtypes of MMA are caused by mutations in cblA (encoded by MMAA) and cblB (encoded by MMAB), which is involved in the synthesis of methylmalonyl-coenzyme A cofactor...
  66. Haglund K, Shimokawa N, Szymkiewicz I, Dikic I. Cbl-directed monoubiquitination of CIN85 is involved in regulation of ligand-induced degradation of EGF receptors. Proc Natl Acad Sci U S A. 2002;99:12191-6 pubmed
    ..Thus, our data demonstrate that Cbl/Cbl-b can mediate polyubiquitination of cargo as well as monoubiquitination of CIN85 to control endosomal sorting and degradation of receptor tyrosine kinases. ..
  67. Lee W, Goh G, Chia J, Boey A, Gunko N, Bard F. The Ubiquitin Ligase CBLC Maintains the Network Organization of the Golgi Apparatus. PLoS ONE. 2015;10:e0138789 pubmed publisher
    ..Depletions of the close homologues CBL and CBLB do not induce any visible defects...
  68. Mazdeh M, Moradi N, Khoshroo E, Shayesteh Z, Taheri M, Sayad A, et al. Down-regulation of TYK2, CBLB and LMP7 genes expression in relapsing-remitting multiple sclerosis patients treated with interferon-beta. J Neuroimmunol. 2018;314:24-29 pubmed publisher
    This study aimed to examine the expression of TYK2, CBLB and LMP7 genes at both mRNA and protein levels in relapsing-remitting MS (RRMS) patients in compare with healthy controls...
  69. Hoppenbrouwers I, Aulchenko Y, Janssens A, Ramagopalan S, Broer L, Kayser M, et al. Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis. J Hum Genet. 2009;54:676-80 pubmed publisher
    ..Several of these risk genes, including CD58 and CLEC16A, are shared by different autoimmune diseases. Fine mapping studies will be needed to determine the functional contributions to distinct autoimmune phenotypes. ..
  70. Venuprasad K. Cbl-b and itch: key regulators of peripheral T-cell tolerance. Cancer Res. 2010;70:3009-12 pubmed publisher
    ..Manipulation of Cbl-b and Itch activities may provide unique opportunities to develop future therapies for immune disorders such as autoimmunity and cancer. ..
  71. Varadé J, Comabella M, Ortiz M, Arroyo R, Fernandez O, Pinto Medel M, et al. Replication study of 10 genes showing evidence for association with multiple sclerosis: validation of TMEM39A, IL12B and CBLB [correction of CLBL] genes. Mult Scler. 2012;18:959-65 pubmed publisher
    ..as a newly identified susceptibility gene in the same study; a gene previously reaching GWAS significance in Italy, CBLB (rs9657904); IL12B (rs6887695, rs10045431), a susceptibility gene shared by diverse autoimmune diseases and, ..
  72. Yan S, Qu X, Xu C, Zhu Z, Zhang L, Xu L, et al. Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells. J Cancer Res Clin Oncol. 2012;138:1279-89 pubmed publisher
    ..Bufalin-induced down-regulation of Cbl-b contributed to the up-regulation of DR4 and DR5, which might be partially mediated by the activation of ERK, JNK and p38 MAPK. ..
  73. Sturner K, Borgmeyer U, Schulze C, Pless O, Martin R. A multiple sclerosis-associated variant of CBLB links genetic risk with type I IFN function. J Immunol. 2014;193:4439-47 pubmed publisher
    ..by genome-wide association studies, three are located near the Casitas B-lineage lymphoma proto-oncogene b gene (CBLB)...
  74. Zhang Y, Qu X, Teng Y, Li Z, Xu L, Liu J, et al. Cbl-b inhibits P-gp transporter function by preventing its translocation into caveolae in multiple drug-resistant gastric and breast cancers. Oncotarget. 2015;6:6737-48 pubmed
    ..Our findings identified a new regulatory mechanism of P-gp transport function in multiple drug-resistant gastric and breast cancers. ..
  75. Bergholdt R, Taxvig C, Eising S, Nerup J, Pociot F. CBLB variants in type 1 diabetes and their genetic interaction with CTLA4. J Leukoc Biol. 2005;77:579-85 pubmed
    ..of an animal model of T1D, the Komeda diabetes-prone rat, have demonstrated that the Casitas-B-lineage lymphoma b (cblb) gene is a major susceptibility gene in the development of diabetes and other autoimmune features of this rat...
  76. Pennock S, Wang Z. A tale of two Cbls: interplay of c-Cbl and Cbl-b in epidermal growth factor receptor downregulation. Mol Cell Biol. 2008;28:3020-37 pubmed publisher
    ..Furthermore, these data ultimately reveal a previously unacknowledged temporal interplay of two major Cbl homologues with the trafficking of EGFR. ..
  77. Ababou A, Pfuhl M, Ladbury J. Novel insights into the mechanisms of CIN85 SH3 domains binding to Cbl proteins: solution-based investigations and in vivo implications. J Mol Biol. 2009;387:1120-36 pubmed publisher
    ..Here we demonstrate that CIN85A and CIN85B use different mechanisms for peptide binding. ..
  78. Zhang Y, Mu X, Li E, Luo Y, Song N, Qu X, et al. The role of E3 ubiquitin ligase Cbl proteins in β-elemene reversing multi-drug resistance of human gastric adenocarcinoma cells. Int J Mol Sci. 2013;14:10075-89 pubmed publisher
    ..Taken together, our results suggest that β-elemene may target P-gp-overexpressing leukemia and gastric cancer cells to enhance the efficacy of DOX treatment. ..
  79. Davies G, Ettenberg S, Coats A, Mussante M, Ravichandran S, Collins J, et al. Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b. Oncogene. 2004;23:7104-15 pubmed
    ..This in vivo result is consistent with the differences in ubiquitin binding observed in vitro between the UBAb and UBAc. This difference in ubiquitin-binding may reflect distinct regulatory functions of c-Cbl and Cbl-b. ..
  80. Nam J, Onodera Y, Mazaki Y, Miyoshi H, Hashimoto S, Sabe H. CIN85, a Cbl-interacting protein, is a component of AMAP1-mediated breast cancer invasion machinery. EMBO J. 2007;26:647-56 pubmed
  81. Horster F, Garbade S, Zwickler T, Aydin H, Bodamer O, Burlina A, et al. Prediction of outcome in isolated methylmalonic acidurias: combined use of clinical and biochemical parameters. J Inherit Metab Dis. 2009;32:630 pubmed publisher
    ..at diagnosis, birth decade, diagnostic work-up, cobalamin responsiveness, enzymatic subgroup (mut(0), mut(-), cblA, cblB) and different aspects of long-term outcome. Results 273 patients were included...
  82. Ceregido M, Garcia Pino A, Ortega Roldan J, Casares S, Lopez Mayorga O, Bravo J, et al. Multimeric and differential binding of CIN85/CD2AP with two atypical proline-rich sequences from CD2 and Cbl-b*. FEBS J. 2013;280:3399-415 pubmed publisher
    ..Together, these results explain how multiple interactions among similar SH3 domains and ligands produce a high degree of diversity in tyrosine kinase, cell adhesion or T-cell signaling pathways. ..
  83. Magnifico A, Ettenberg S, Yang C, Mariano J, Tiwari S, Fang S, et al. WW domain HECT E3s target Cbl RING finger E3s for proteasomal degradation. J Biol Chem. 2003;278:43169-77 pubmed
  84. Qu X, Sada K, Kyo S, Maeno K, Miah S, Yamamura H. Negative regulation of FcepsilonRI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b. Blood. 2004;103:1779-86 pubmed
    ..These results suggest that Cbl-b is a negative regulator of both Lyn-Syk-LAT and Gab2mediated complementary signaling pathways in FcepsilonRI-mediated mast cell activation. ..
  85. Yu J, Zhao H, Zhang Y, Liu Y, Yao L, Li X, et al. Ubiquitin ligase Cbl-b acts as a negative regulator in discoidin domain receptor 2 signaling via modulation of its stability. FEBS Lett. 2014;588:1509-14 pubmed publisher
    ..Thus, Cbl-b, by promoting the ubiquitination and degradation of DDR2, functions as a negative regulator in the DDR2 signaling pathway. ..
  86. Yang W, Jin R, Jiang C, Wang X, Shu J, Li L, et al. E3 ubiquitin ligase Cbl-b suppresses human ORMDL3 expression through STAT6 mediation. FEBS Lett. 2015;589:1975-80 pubmed publisher
    ..Our results show that Cbl-b suppresses human ORMDL3 expression through STAT6. ..
  87. Doníz Padilla L, Martínez Jiménez V, Niño Moreno P, Abud Mendoza C, Hernández Castro B, Gonzalez Amaro R, et al. Expression and function of Cbl-b in T cells from patients with systemic lupus erythematosus, and detection of the 2126 A/G Cblb gene polymorphism in the Mexican mestizo population. Lupus. 2011;20:628-35 pubmed publisher
    ..In addition, the possible association of SLE and a single nucleotide polymorphism (SNP) of the Cblb gene was determined...
  88. Wirnsberger G, Zwolanek F, Asaoka T, Kozieradzki I, Tortola L, Wimmer R, et al. Inhibition of CBLB protects from lethal Candida albicans sepsis. Nat Med. 2016;22:915-23 pubmed publisher
    ..Here we report that the E3 ubiquitin ligase CBLB controls proximal CLR signaling in macrophages and dendritic cells...
  89. Ohira M, Morohashi A, Nakamura Y, Isogai E, Furuya K, Hamano S, et al. Neuroblastoma oligo-capping cDNA project: toward the understanding of the genesis and biology of neuroblastoma. Cancer Lett. 2003;197:63-8 pubmed
    ..We have identified approximately 500 differentially expressed genes between favorable and unfavorable subsets of NBL, among which more than 250 were the genes with unknown function. ..
  90. Caligiuri M, Briesewitz R, Yu J, Wang L, Wei M, Arnoczky K, et al. Novel c-CBL and CBL-b ubiquitin ligase mutations in human acute myeloid leukemia. Blood. 2007;110:1022-4 pubmed
    ..Short-interfering RNA knockdown of mutant c-CBL present in MOLM-13 cells was growth inhibitory. In summary, novel mutations in c-CBL and CBL-b have been identified in human AML and may represent potential targets for novel therapeutics. ..