MassIVE MSV000096042

Partial Public PXD056612

AMBRA1 controls the translation of immune-specific genes in T lymphocytes

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Description

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. During 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 resist 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 loading on select mRNAs that plays a key role in balancing TCR signaling with cell cycle regulation pathways. We also found that AMBRA1 itself is translational 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 that governs TCR signaling, cell cycle progression and T cell death. [doi:10.25345/C53F4M06S] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Protein translation, Fas signaling pathway, AMBRA1, T cell death, T cell activation

Contact

Principal Investigators:
(in alphabetical order) 		Michael J. Lenardo, 1Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, NIAID, National Institutes of Health, Bethesda, MD 20814, USA
Submitting User: BHaeup

Publications

Gottlieb S, Shang W, Ye D, Kubo S, Jiang PD, Shafer S, Xu L, Zheng L, Park AY, Song J, Chan W, Zeng Z, He T, Schwarz B, Häupl B, Oellerich T, Lenardo MJ, Yao Y.
AMBRA1 controls the translation of immune-specific genes in T lymphocytes.
Proc Natl Acad Sci U S A. 2024 Oct 29;121(44):e2416722121. Epub 2024 Oct 22.

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