Regulation of T cell development by the deubiquitinating enzyme CYLD. Journal   Nature immunology. Citation   Nat Immunol. 7(4):411-7 Publication date   2006 Apr Authors   Reiley WW Zhang M Jin W Losiewicz M Donohue KB Norbury CC Sun SC Investigators   Christopher Norbury Shao-Cong Sun Min-Ying Zhang Grant agencies   National Institute of Allergy and Infectious Diseases National Center for Research Resources National Cancer Institute Grants   NIAID AI056094 NIAID AI057555 NCRR C06 RR-15428-01 NCI CA94922 MeSH headings   Receptors, Antigen, T-Cell T-Lymphocytes Tumor Suppressor Proteins MeSH qualifiers   immunology 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.