ASK1 mediates Nur77 expression in T-cell receptor mediated thymocyte apoptosis

• Main Authors: Huo, Jianxin, Xu, Shengli, Lam, Kong-Peng
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Biological sciences; ASK1; p38
• Online Access: https://hdl.handle.net/10356/145604
• Institution: Nanyang Technological University

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK) that activates downstream JNK and p38 mitogen-activated protein kinase (MAPK) to relay death signals into cells in response to various environmental stress. However, whether ASK1 plays a role in T cell receptor (TCR)-mediated apoptosis of thymocytes is unclear. Here, we show that ASK1 is activated upon TCR stimulation and plays an important role in TCR-mediated apoptosis of thymocytes by triggering downstream JNK and p38 signaling cascades. Mechanistically, ASK1-JNK/p38 signaling leads to the upregulation of neuron-derived clone 77 (Nur77), a critical pro-apoptotic protein involved in TCR-mediated apoptosis of thymocytes. Furthermore, we demonstrate that the activation of ASK1 is negatively modulated by Akt upon TCR stimulation. Thus, our results identify a previously unappreciated signaling mechanism involving ASK1 in TCR-mediated apoptosis of thymocytes.