| Autor: |
Gottlieb, Simone, Wanjing Shang, Deji Ye, Satoshi Kubo, Ping Du Jiang, Shafer, Samantha, Leilei Xu, Lixin Zheng, Park, Ann Y., Jian Song, Waipan Chan, Zhiqin Zeng, Tingyan He, Schwarz, Benjamin, Häupl, Björn, Oellerich, Thomas, Lenardo, Michael J., Yikun Yao |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 10/29/2024, Vol. 121 Issue 44, p1-12, 19p |
| Abstrakt: |
T cell receptor (TCR) engagement causes a global cellular response that entrains signaling pathways, cell cycle regulation, and cell death. The molecular regulation of mRNA translation in these processes is poorly understood. Using a whole-genome CRISPR screen for regulators of CD95 (FAS/APO-1)-mediated T cell death, we identified AMBRA1, a protein previously studied for its roles in autophagy, E3 ubiquitin ligase activity, and cyclin regulation. T cells lacking AMBRA1 resisted FAS-mediated cell death by down-regulating FAS expression at the translational level. We show that AMBRA1 is a vital regulator of ribosome protein biosynthesis and ribosome loading on select mRNAs, whereby it plays a key role in balancing TCR signaling with cell cycle regulation pathways. We also found that AMBRA1 itself is translationally controlled by TCR stimulation via the CD28-PI3K-mTORC1-EIF4F pathway. Together, these findings shed light on the molecular control of translation after T cell activation and implicate AMBRA1 as a translational regulator governing TCR signaling, cell cycle progression, and T cell death. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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