Regulation of T cell development by the deubiquitinating enzyme CYLD.
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.
Reiley
William W
WW
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Zhang
Minying
M
Jin
Wei
W
Losiewicz
Mandy
M
Donohue
Keri B
KB
Norbury
Christopher C
CC
Sun
Shao-Cong
SC
D000818:Animals; D003433:Crosses, Genetic; D007113:Immunity, Innate / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D025521:Tumor Suppressor Proteins / Q000276:immunology* / Q000378:metabolism; D025801:Ubiquitin / Q000276:immunology / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse