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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
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.
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.
c-Cbl negatively regulates IFN-beta (zeige IFNB1 Proteine) signaling and cellular antiviral response by promoting IRF3 (zeige IRF3 Proteine) ubiquitination and degradation.
This study demonstrate an unprecedented role for c-Cbl in microglia-mediated neuroinflammation involving PI3K/Akt (zeige AKT1 Proteine)/NF-kappaB (zeige NFKB1 Proteine) pathway.
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 (zeige FRAP1 Proteine) signaling.
mutant CBL proteins effectively compete with the remaining wild type CBL-B and juxtapose tyrosine kinase (zeige TYRO3 Proteine)-binding domain-associated protein tyrosine kinases with proline-rich region-associated signaling proteins to hyper-activate signaling downstream of hematopoietic growth factor (zeige IL-3 Proteine) receptors
results demonstrate that c-Cbl mediates the ubiquitination/degradation of integrin beta1, which leads to COMP (zeige COMP Proteine) deficiency-induced dilated cardiomyopathy.
Gem (zeige GEM Proteine), a gene encoding a GTPase (zeige RACGAP1 Proteine) that is upregulated by Cbl(Q367P) , enhanced hematopoietic stem cell activity and induced myeloid cell proliferation. In addition, Evi1 (zeige MECOM Proteine), a gene encoding a transcription factor, was found to cooperate with Cbl(Q367P) and progress CMML to AML (zeige RUNX1 Proteine).
Fasudil, a clinically safe ROCK inhibitor, decreases disease burden in a Cbl/Cbl-b deficiency-driven murine model of myeloproliferative disorders.
Authors observed that delta-catenin (zeige CTNND2 Proteine) plays a key role in EGFR (zeige EGFR Proteine) stability and downstream signaling. delta-Catenin (zeige CTNND2 Proteine) competes with c-Cbl for EGFR (zeige EGFR Proteine) binding, which results in a reduction of binding between c-Cbl and EGFR (zeige EGFR Proteine) and thus decreases the ubiquitination of EGFR (zeige EGFR Proteine).
c-CBL might play a role in the pathogenesis of inflammatory dermatoses and cutaneous T-cell lymphoma
Two germline de novo mutations in CBL were identified in patients with infancy-onset severe Moyamoya angiopathy who also presented subtle signs of RASopathy.
Patients harbouring ASXL1 (zeige ASXL1 Proteine) and/or CBL mutations (n = 8, 8 deaths, median OS = 11 months) had a significantly worse OS as compared to those without either mutation (n = 11, 4 deaths, median OS = 84 months) (P = 0.0002) (Fig 1a).
the loss of c-Cbl activity significantly enhanced nuclear beta-catenin (zeige CTNNB1 Proteine) and colorectal cancer tumor growth in cell culture and a mouse xenograft model.
we have shown that c-CBL plays a supportive role in the proliferation, migration and invasion of human melanoma cells.
Findings show for this first time that ATG9A (zeige ATG9A Proteine) loss in trastuzumab resistant cells allowed Her2 (zeige ERBB2 Proteine) to escape from lysosomal targeted degradation through K63 poly-ubiquitination via c-Cbl.
These results suggest MET overexpression is related to altered c-CBL expression in head and neck squamous cell carcinoma, which may influence tumorigenesis
This study identified a new regulatory axis in which miR (zeige MLXIP Proteine)-124-3p and CBL regulate the proliferation and invasion of breast cancer cells.
This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia. Mutations in this gene are also the cause of Noonan syndrome-like disorder.
E3 ubiquitin-protein ligase CBL
, casitas B-lineage lymphoma proto-oncogene
, proto-oncogene c-CBL
, signal transduction protein CBL
, Cas-Br-M (murine) ecotropic retroviral transforming sequence
, RING finger protein 55
, fragile site, folic acid type, rare, fra(11)(q23.3)
, oncogene CBL2
, proto-oncogene c-Cbl
, Casitas B-lineage lymphoma