Regulation of T cell development by the deubiquitinating enzyme CYLD

Abstract

T cell receptor signaling is essential for the generation and maturation of T lymphocyte precursors. Here we identify the deubiquitinating enzyme CYLD as a positive regulator of proximal T cell receptor signaling in thymocytes. CYLD physically interacted with active Lck and promoted recruitment of active Lck to its substrate, Zap70. CYLD also removed both Lys 48– and Lys 63–linked polyubiquitin chains from Lck. Because of a cell-autonomous defect in T cell development, CYLD-deficient mice had substantially fewer mature CD4⁺ and CD8⁺ single-positive thymocytes and peripheral T cells.