CBL是抑癌基因，编码蛋白为泛素连接酶E3，其介导编受体酪氨酸激酶的降解。CBL家族的连接酶E3选择性地和负向地调节激活后的受体酪氨酸激酶，包括EGFR、PDGFR、CSF-1R、MET、FLT3，通过泛素化来靶向这些蛋白以通过蛋白酶体将靶向蛋白降解。除了受体酪氨酸激酶调节外，CBL-B还参与T细胞活化和外周T细胞耐受性。CBL胚系突变与发育迟缓和幼年型髓单核细胞白血病的易感性相关。在骨髓增生异常综合征，肺腺癌和皮肤黑素瘤等多个癌种中已经检测到CBL的体细胞突变。在BCR-ABL重排突变型慢性粒细胞白血病（CML）中，BCR-ABL融合导致CBL表达下调，导致下游信号通路的异常激活。

CBL is an E3 ubiquitin-ligase and proto-oncogene that mediates degradation of receptor tyrosine kinases. CBL family E3 ligases selectively and negatively regulate activated receptor tyrosine kinases, including EGFR, PDGFR, CSF-1R, MET, and FLT3, through ubiquitylation that targets these proteins for degradation by the proteasome. The activity of CBL is required to negatively regulate various signaling pathways, most commonly in hematopoietic and immune cells. In addition to receptor tyrosine kinase regulation, CBL-b is also involved in T cell activation and peripheral T cell tolerance. Germline mutations in CBL result in developmental delays and a predisposition for juvenile myelomonocytic leukemia. Somatic alterations in CBL have been identified in several human cancers including myelodysplastic syndromes, lung adenocarcinoma and cutaneous melanoma. In BCR-ABL rearranged mutant chronic myeloid leukemia (CML), CBL expression is downregulated by the BCR-ABL fusion leading to aberrant activation of downstream signaling pathways.

GeneCards OncoKB My Cancer Genome