Cbl proto-oncogene (c-Cbl) (CBL)

Cbl proto-oncogene (c-Cbl), encoded by the CBL gene, is an E3 ubiquitin-protein ligase and a founding member of the Cbl protein family[4][1]. It acts as a critical regulator of cell signaling by targeting activated receptor protein tyrosine kinases (RTKs) for ubiquitination—marking them for endocytosis and lysosomal degradation, thereby attenuating downstream signaling[5][2][4][1]. Its modular structure includes a tyrosine kinase binding (TKB) domain, a RING finger domain responsible for E3 ligase activity, a proline-rich region for protein-protein interactions, and a C-terminal ubiquitin-associated domain[4][2][5]. CBL also works as an adaptor protein in signal transduction, sometimes recruiting signaling molecules to RTKs[5][2]. Mutations in CBL are found in several myeloid neoplasms and play a role in oncogenesis, especially when the negative regulatory (E3 ligase) function is lost but its adaptor function remains active[1][5]. The CBL gene and its protein products are thus considered significant therapeutic targets in cancer biology, particularly in hematologic malignancies[1][4][5].

Other names

C-CBLCBL2FRA11BNSLLRNF55

Negative regulation of receptor tyrosine kinase signaling by ubiquitination and lysosomal degradation of activated RTKs[5][1]; Adaptor function for recruiting signaling molecules to RTKs[5]