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Otud7b facilitates ...
Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination
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- Hu, Hongbo (författare)
- Sichuan University, Peoples R China; University of Texas MD Anderson Cancer Centre, TX 77030 USA
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- Wang, Hui (författare)
- Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,University of Texas MD Anderson Cancer Centre, TX 77030 USA
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- Xiao, Yichuan (författare)
- University of Texas MD Anderson Cancer Centre, TX 77030 USA; Shanghai Jiao Tong University, Peoples R China
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- Jin, Jin (författare)
- University of Texas MD Anderson Cancer Centre, TX 77030 USA; Zhejiang University, Peoples R China
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- Chang, Jae-Hoon (författare)
- University of Texas MD Anderson Cancer Centre, TX 77030 USA; Yeungnam University, South Korea
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- Zou, Qiang (författare)
- University of Texas MD Anderson Cancer Centre, TX 77030 USA
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- Xie, Xiaoping (författare)
- University of Texas MD Anderson Cancer Centre, TX 77030 USA
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- Cheng, Xuhong (författare)
- University of Texas MD Anderson Cancer Centre, TX 77030 USA
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- Sun, Shao-Cong (författare)
- University of Texas MD Anderson Cancer Centre, TX 77030 USA; University of Texas Houston, TX 77030 USA
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(creator_code:org_t)
- 2016-02-22
- 2016
- Engelska.
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Ingår i: Journal of Experimental Medicine. - : ROCKEFELLER UNIV PRESS. - 0022-1007 .- 1540-9538. ; 213:3, s. 399-414
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://rupress.org/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
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