Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Notch-Induced Endoplasmic Reticulum-Associated Degradation Governs Thymocyte β-Selection Signals from the pre-T cell receptor and Notch coordinately instruct {beta}-selection of CD4-CD8- double negative (DN) thymocytes to generate {beta} T cells in the thymus. However, how these signals ensure a high-fidelity proteome and safeguard the clonal diversification of the pre- selection TCR repertoire given the considerable translational activity imposed by {beta}-selection is largely unknown. Here, we identify the endoplasmic reticulum (ER)-associated degradation (ERAD) machinery as a critical proteostasis checkpoint during {beta}-selection. Expression of the SEL1L-HRD1 complex, the most conserved branch of ERAD, is directly regulated by the transcriptional activity of the Notch intracellular domain. Deletion of Sel1l impaired DN3 to DN4 thymocyte transition and severely impaired {beta} T cell development. Mechanistically, Sel1l deficiency induced unresolved ER stress that triggered thymocyte apoptosis through the PERK pathway. Accordingly, genetically inactivating PERK rescued T cell development from Sel1l- deficient thymocytes. Our study reveals a critical developmental signal controlled proteostasis mechanism that enforces T cell development to ensure a healthy adaptive immunity.
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The categories of this paper are: biophysics
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The categories of this paper are: paleontology
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The categories of this paper are: communication
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The categories of this paper are: zoology
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The categories of this paper are: neuroscience
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The categories of this paper are: genomics
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The categories of this paper are: toxicology
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The categories of this paper are: and
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The categories of this paper are: developmental
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The categories of this paper are: epidemiology
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The categories of this paper are: scientific
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The categories of this paper are: synthetic
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The categories of this paper are: molecular
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The categories of this paper are: evolutionary
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The categories of this paper are: behavior
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The categories of this paper are: biochemistry