CBLB
Description
The CBLB (Cbl proto-oncogene B) is a protein-coding gene located on chromosome 3.
CBLB, a human gene, encodes a protein with diverse functions in regulating cellular signaling pathways, primarily through its role as an E3 ubiquitin ligase.
CBLB acts as an E3 ubiquitin ligase, accepting ubiquitin from specific E2 enzymes and transferring it to target proteins, leading to their degradation by the proteasome. This protein plays a crucial role in regulating signaling pathways, including those initiated by the T-cell receptor (TCR), B-cell receptor (BCR), and the high affinity immunoglobulin epsilon receptor (FCER1). In naive T cells, CBLB inhibits VAV1 activation upon TCR engagement, requiring CD28 costimulation for proliferation and IL-2 production. It also promotes PIK3R1/p85 ubiquitination, hindering its recruitment to the TCR and subsequent activation. In activated T cells, CBLB inhibits PLCG1 activation and calcium mobilization, leading to anergy. In B cells, CBLB ubiquitinates SYK, promoting its degradation by the proteasome. It can also promote SRC ubiquitination and may be involved in EGFR ubiquitination and internalization. CBLB may be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In conjunction with CBL, CBLB is essential for proper feedback inhibition of the ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway through ubiquitination and internalization of PDGFRA.
CBLB is also known as ADMIO3, Cbl-b, Nbla00127, RNF56.
