E3 ubiquitin-protein ligase CBL-B (Casitas B-lineage lymphoma proto-oncogene B) (Cbl-b or CBLB)

E3 ubiquitin-protein ligase CBL-B (Cbl-b) is a RING-type E3 ubiquitin ligase that functions as a critical negative regulator of immune cell activation[2][3]. The protein catalyzes the transfer of ubiquitin to substrate proteins, targeting them for proteasomal degradation, and plays a central role in maintaining immune homeostasis by suppressing T cell receptor, B cell receptor, and high-affinity immunoglobulin E receptor signaling[3]. Cbl-b inhibits antigen recognition and slows cell cycle progression during CD4+ T cell expansion, promoting T cell anergy and maintaining peripheral immune tolerance[1]. In disease contexts, Cbl-b dysfunction is implicated in autoimmune diseases such as systemic lupus erythematosus and multiple sclerosis, while Cbl-b inhibition or silencing is emerging as a promising therapeutic strategy to enhance anti-tumor immunity by unleashing lymphocyte effector functions[2]. Research demonstrates that deficiency or silencing of Cbl-b in CD8+ T cells enhances their anti-tumor activity and improves cancer vaccine efficacy, supporting its development as a target for cancer immunotherapy and potentially other conditions requiring enhanced immune responses[2].

Other names

Cbl Proto-Oncogene BRNF56 (RING finger protein 56)RING-Type E3 Ubiquitin Transferase CBL-BCbl Proto-Oncogene B, E3 Ubiquitin Protein Ligase

Cbl-b inhibition/silencing — Blocks the ubiquitin ligase activity of Cbl-b, thereby preventing degradation of signaling molecules and enhancing immune cell activation. Enhancement of T cell receptor signaling — By inhibiting Cbl-b, TCR signal transduction is enhanced, increasing T cell proliferation and effector functions. Reversal of T cell anergy — Cbl-b inhibition promotes IL-2 production and prevents anergy induction in CD4+ T cells. Enhanced CAR-T cell function — Cbl-b deficiency in chimeric antigen receptor T cells improves their anti-tumor efficacy.