Jurkat细胞
T细胞受体
细胞生物学
信号转导
泛素
受体
功能(生物学)
细胞
生物
细胞信号
T细胞
遗传学
基因
免疫系统
作者
Akhee Sabiha Jahan,Maxime Lestra,Lee Kim Swee,Yuxin Fan,Mart M. Lamers,Fikadu G. Tafesse,Christopher S. Theile,Eric Spooner,Roberto Bruzzone,Hidde L. Ploegh,Sumana Sanyal
标识
DOI:10.1073/pnas.1521763113
摘要
Significance We used an unbiased screening strategy to capture deubiquitylases that participate in T cell receptor signaling in primary cells under physiological settings. We identified ubiquitin-specific peptidase (Usp) 12 as a crucial component of TCR expression at the cell surface, and found supporting evidence for its function by creating an inducible genetic knockout in Jurkat cells. Using proximity-based labeling, we identified LAT and Trat1 as substrates of Usp12. In Usp12-deficient cells, both LAT and Trat1 are ubiquitin-modified and lysosomally degraded, thus down-regulating TCR surface expression. Our data define a role of Usp12 in the TCR signaling pathway for the first time, to our knowledge. These results underscore the importance of deubiquitylases in fine-tuning signaling cascades and provide a basis for the screening of small molecules to identify potential inhibitors.
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