Casitas B-lineage lymphoma proto-oncogene (c-Cbl)

Casitas B-lineage lymphoma proto-oncogene (c-Cbl) is an E3 ubiquitin-protein ligase that functions as a crucial negative regulator of signal transduction, specifically by mediating the ubiquitination and subsequent degradation or recycling of activated receptor tyrosine kinases (such as EGFR, VEGFR, FGFR, PDGFR, c-Met), thereby attenuating their downstream signaling[1][4][5][6][9]. c-Cbl plays important roles in controlling cell proliferation, differentiation, immune signaling, and cytoskeletal regulation[1][2][6]. Mutations in CBL, especially loss-of-function mutations, drive abnormal signaling and contribute to the pathogenesis of various cancers, prominently myeloid neoplasms and some solid tumors[3][4][5][6][8]. Recent research has shown c-Cbl's involvement in the regulation of immune checkpoints such as PD-1, impacting tumor immunity and suggesting potential for therapeutic exploitation in oncology and immunotherapy[2][4]. c-Cbl contains several functionally distinct domains, including an N-terminal tyrosine kinase binding domain (TKB), a RING finger E3 ligase motif, a proline-rich region, and a C-terminal ubiquitin-associated domain[1][5][6].

Other names

CBLCBL2FRA11BNSLLRNF55E3 ubiquitin-protein ligase CBL

Ubiquitination and proteasomal degradation of substrate proteins, including receptor tyrosine kinases (e.g. EGFR, PDGFR, VEGFR, FGFR, c-Met), negative regulation of immune checkpoint protein PD-1