Reiley William W, Zhang Minying, Jin Wei, Losiewicz Mandy, Donohue Keri B, Norbury Christopher C, Sun Shao-Cong
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Nat Immunol. 2006 Apr;7(4):411-7. doi: 10.1038/ni1315. Epub 2006 Feb 26.
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.
T细胞受体信号传导对于T淋巴细胞前体的产生和成熟至关重要。在此，我们确定去泛素化酶CYLD是胸腺细胞中近端T细胞受体信号传导的正向调节因子。CYLD与活性Lck发生物理相互作用，并促进活性Lck募集至其底物Zap70。CYLD还从Lck上去除了赖氨酸48和赖氨酸63连接的多聚泛素链。由于T细胞发育存在细胞自主性缺陷，CYLD缺陷小鼠的成熟CD4(+)和CD8(+)单阳性胸腺细胞及外周T细胞数量大幅减少。
