Semin Immunol, vol. 19, issue 3 (2007) pp. 206-214
The family of the Casitas B-lineage Lymphoma (Cbl) proteins, c-Cbl, Cbl-b, and Cbl-3, function as E3 ubiquitin ligases and molecular adaptors. In particular, Cbl-b acts as a gatekeeper in T cell activation that controls activation thresholds and the requirement for co-stimulation. Loss of Cbl-b expression renders animals susceptible to antigen-triggered autoimmunity suggesting that Cbl-b is a key autoimmunity gene. In addition, Cbl-b plays a critical role in T cell anergy and escape from regulatory T cells (Treg) suppression. Modulation of Cbl-b might provide us with a unique opportunity for future immune treatment of human disorders such as autoimmunity, immunodeficiency, or cancer.
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