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论文题目: Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination
英文论文题目: Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination
第一作者: Hu, HB; Wang, H; Xiao, YC; Jin, J; Chang, JH; Zou, Q; Xie, XP; Cheng, XH; Sun, SC
英文第一作者: Hu, HB; Wang, H; Xiao, YC; Jin, J; Chang, JH; Zou, Q; Xie, XP; Cheng, XH; Sun, SC
联系作者: Sun, SC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
英文联系作者: Sun, SC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
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发表年度: 2016
卷: 213
期: 3
页码: 399-414
摘要: Signal transduction from the T cell receptor (TCR) is crucial for T cell-mediated immune responses and, when deregulated, also contributes to the development of autoimmunity. How TCR signaling is regulated is incompletely understood. In this study, we demonstrate a ubiquitin-dependent mechanism in which the deubiquitinase Otud7b has a crucial role in facilitating TCR signaling. Upon TCR ligation, Otud7b is rapidly recruited to the tyrosine kinase Zap70, a central mediator of TCR-proximal signaling. Otud7b deficiency attenuates the activation of Zap70 and its downstream pathways and impairs T cell activation and differentiation, rendering mice refractory to T cell-mediated autoimmune and inflammatory responses. Otud7b facilitated Zap70 activation by deubiquitinating Zap70, thus preventing the association of Zap70 with the negative-regulatory phosphatases Sts1 and Sts2. These findings establish Otud7b as a positive regulator of TCR-proximal signaling and T cell activation, highlighting the importance of deubiquitination in regulating Zap70 function.
英文摘要: Signal transduction from the T cell receptor (TCR) is crucial for T cell-mediated immune responses and, when deregulated, also contributes to the development of autoimmunity. How TCR signaling is regulated is incompletely understood. In this study, we demonstrate a ubiquitin-dependent mechanism in which the deubiquitinase Otud7b has a crucial role in facilitating TCR signaling. Upon TCR ligation, Otud7b is rapidly recruited to the tyrosine kinase Zap70, a central mediator of TCR-proximal signaling. Otud7b deficiency attenuates the activation of Zap70 and its downstream pathways and impairs T cell activation and differentiation, rendering mice refractory to T cell-mediated autoimmune and inflammatory responses. Otud7b facilitated Zap70 activation by deubiquitinating Zap70, thus preventing the association of Zap70 with the negative-regulatory phosphatases Sts1 and Sts2. These findings establish Otud7b as a positive regulator of TCR-proximal signaling and T cell activation, highlighting the importance of deubiquitination in regulating Zap70 function.
刊物名称: JOURNAL OF EXPERIMENTAL MEDICINE
英文刊物名称: JOURNAL OF EXPERIMENTAL MEDICINE
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学科: Immunology; Medicine, Research & Experimental
英文学科: Immunology; Medicine, Research & Experimental
影响因子: 11.991
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论文类别: Article
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