CBL
CBL (Cbl proto-oncogene, also known as c-Cbl, RNF55 and CBL2) is a RING finger E3 ubiquitin ligase that acts as a negative regulator of many signalling pathways. It marks activated cell surface receptors for degradation by the proteasome. Browse Assay Genie's current range of CBL research reagents below, or read on for the biology behind the target.
CBL accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and transfers it to substrates, promoting their degradation by the proteasome. It recognises activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR, and ubiquitinates them to terminate signalling. It also targets membrane-bound SRC family kinases such as HCK and SRC, and ubiquitinates EGFR and SPRY2.
The CBL protein contains a RING finger domain and an N-terminal phosphotyrosine binding domain. The latter allows it to interact with many tyrosine-phosphorylated substrates and direct them to proteasomal degradation. In T-cell biology, CBL is involved in LAG3-mediated inhibition of TCR signalling: after ligand binding to LAG3, it catalyses 'Lys-63'-linked ubiquitination of LAG3, which releases the LAG3 C-terminus from the membrane and starts a signal that prevents TCR activation. CBL also ubiquitinates NECTIN1 after NECTIN1 associates with herpes simplex virus 1 envelope glycoprotein D, removing NECTIN1 from the cell surface.
CBL participates in signal transduction in haematopoietic cells and helps regulate osteoblast differentiation and apoptosis. It is essential for osteoclastic bone resorption, where the Tyr-731 phosphorylated form recruits phosphatidylinositol 3-kinase to the cell membrane. Together with CBLB, it supports feedback inhibition of ciliary PDGFRA signalling through ubiquitination and internalisation of the receptor. The CBL gene is a proto-oncogene found mutated or translocated in many cancers, including acute myeloid leukaemia. CGG repeat expansion in the 5' UTR has been associated with Jacobsen syndrome, and mutations cause a Noonan syndrome-like disorder. Earlier names include Cas-Br-M (murine) ecotropic retroviral transforming sequence.
CBL ubiquitinates activated receptors such as KIT, PDGFRA and KDR, making it a key enzyme for studying how receptor signalling is terminated.
As a RING E3 ligase that passes ubiquitin from E2 enzymes to substrates, CBL is a model for substrate targeting and proteasomal degradation.
CBL is a proto-oncogene mutated or translocated in many cancers, including acute myeloid leukaemia, so it features in oncogenic signalling studies.
CBL contributes to LAG3-mediated inhibition of TCR signalling and is essential for osteoclastic bone resorption.
CBL is an E3 ubiquitin-protein ligase that accepts ubiquitin from E2 enzymes and transfers it to substrates, promoting their proteasomal degradation. It acts as a negative regulator of many signalling pathways by ubiquitinating activated receptor tyrosine kinases and SRC family kinases.
CBL is also called c-Cbl, RNF55 and CBL2. Its HGNC name is Cbl proto-oncogene, and earlier names include Cas-Br-M (murine) ecotropic retroviral transforming sequence. It belongs to the RING finger proteins and the Cbl proto-oncogene family, which also includes CBLB.
The CBL gene is mutated or translocated in many cancers, including acute myeloid leukaemia. Mutations also cause a Noonan syndrome-like disorder, and CGG repeat expansion in its 5' UTR has been associated with Jacobsen syndrome. A mouse ortholog, Cbl, exists; check the datasheet of any product for its validated reactivity.
Other Cbl family members, receptor tyrosine kinases and signalling proteins regulated by CBL-mediated ubiquitination.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P22681; product specifications from Assay Genie datasheets.