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

ASK1 mediates Nur77 expression in T-cell receptor mediated thymocyte apoptosis
Title:
ASK1 mediates Nur77 expression in T-cell receptor mediated thymocyte apoptosis
Other Titles:
Cells
Publication Date:
01 March 2020
Citation:
Huo, J.; Xu, S.; Lam, K.-P. ASK1 Mediates Nur77 Expression in T-Cell Receptor Mediated Thymocyte Apoptosis. Cells 2020, 9, 585.
Abstract:
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.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
Description:
ISSN:
2073-4409
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