Cbl proto-oncogene B (CBL-B)

Cbl proto-oncogene B (CBL-B) is an E3 ubiquitin-protein ligase and signaling adaptor protein that plays a crucial role in regulating immune cell activation and receptor tyrosine kinase signaling. It is a member of the CBL family, which also includes c-CBL and CBL-c, and is characterized by a tyrosine kinase binding (TKB) domain, a RING finger domain that mediates ubiquitin transfer, and a proline-rich region involved in protein-protein interactions[1][3]. CBL-B primarily acts to negatively regulate T cell and NK cell activation by ubiquitinating key signaling components, thus preventing overactive immune responses. Loss-of-function mutations in CBLB have been implicated in autoimmunity and certain cancers, while gain of function or mutations that affect its regulatory domains are associated with tumorigenesis, particularly myeloid neoplasms[2][3]. Interest in targeting CBL-B stems from its dual role in cancer and immune regulation, with preclinical efforts to develop CBL-B inhibitors as novel immunotherapeutic agents aiming to boost antitumor immunity[2].

Other names

CBLBE3 ubiquitin-protein ligase CBL-BRNF56

Ubiquitination and targeting of activated receptor tyrosine kinases for lysosomal degradation Disruption of CBL-B E3 ligase function or inhibition of its adaptor function can alter downstream signaling, enhance T-cell and NK cell activity, and modulate antitumor immunity[1][2].