TCR-induced,PKC-θ-mediated NF-κB activation is regulated by a caspase-8–caspase-9–caspase-3 cascade |
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Authors: | Yixia Zhao Minxiang Lei Zhaoyuan Wang Guilin Qiao Tianlun Yang Jian Zhang |
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Institution: | 1. Department of Cardiology, Xiangya Hospital, Central South University, Hunan 41000, China;2. Section of Nephrology, Department of Medicine, The University of Chicago, IL 60637, United States;3. Department of Microbial Infection and Immunity, The Ohio State University, OH 43210, United States |
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Abstract: | It has been documented that caspase-8, a central player in apoptosis, is also crucial for TCR-mediated NF-κB activation. However, whether other caspases are also involved this process is unknown. In this report, we showed that in addition to caspase-8, caspase-9 is required for TCR-mediated NF-κB activation. Caspase-9 induces activation of PKC-θ, phosphorylation of Bcl10 and NF-κB activation in a caspase-3-dependent manner, but it appears that Bcl10 phosphorylation is uncoupled from NF-κB activation. Furthermore, caspase-8 lies upstream of caspase-9 during T cell activation. Therefore, TCR ligation elicits a caspase cascade involving caspase-8, caspase-9 and caspase-3 which initiates PKC-θ-dependent pathway leading to NF-κB activation and PKC-θ-independent Bcl10 phosphorylation which limits NF-kB activity. |
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Keywords: | T cell activation Caspase-9 NF-κB |
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