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      Protein synthesis, degradation, and energy metabolism in T cell immunity

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          Abstract

          T cell activation, proliferation, and differentiation into effector and memory states involve massive remodeling of T cell size and molecular content and create a massive increase in demand for energy and amino acids. Protein synthesis is an energy- and resource-demanding process; as such, changes in T cell energy production are intrinsically linked to proteome remodeling. In this review, we discuss how protein synthesis and degradation change over the course of a T cell immune response and the crosstalk between these processes and T cell energy metabolism. We highlight how the use of high-resolution mass spectrometry to analyze T cell proteomes can improve our understanding of how these processes are regulated.

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          Most cited references125

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          The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation. Copyright © 2012 Elsevier Inc. All rights reserved.
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            A guide to immunometabolism for immunologists.

            In recent years a substantial number of findings have been made in the area of immunometabolism, by which we mean the changes in intracellular metabolic pathways in immune cells that alter their function. Here, we provide a brief refresher course on six of the major metabolic pathways involved (specifically, glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis and amino acid metabolism), giving specific examples of how precise changes in the metabolites of these pathways shape the immune cell response. What is emerging is a complex interplay between metabolic reprogramming and immunity, which is providing an extra dimension to our understanding of the immune system in health and disease.
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              On the Dependency of Cellular Protein Levels on mRNA Abundance.

              The question of how genomic information is expressed to determine phenotypes is of central importance for basic and translational life science research and has been studied by transcriptomic and proteomic profiling. Here, we review the relationship between protein and mRNA levels under various scenarios, such as steady state, long-term state changes, and short-term adaptation, demonstrating the complexity of gene expression regulation, especially during dynamic transitions. The spatial and temporal variations of mRNAs, as well as the local availability of resources for protein biosynthesis, strongly influence the relationship between protein levels and their coding transcripts. We further discuss the buffering of mRNA fluctuations at the level of protein concentrations. We conclude that transcript levels by themselves are not sufficient to predict protein levels in many scenarios and to thus explain genotype-phenotype relationships and that high-quality data quantifying different levels of gene expression are indispensable for the complete understanding of biological processes.
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                Author and article information

                Contributors
                d.a.cantrell@dundee.ac.uk
                Journal
                Cell Mol Immunol
                Cell Mol Immunol
                Cellular and Molecular Immunology
                Nature Publishing Group UK (London )
                1672-7681
                2042-0226
                4 January 2022
                4 January 2022
                March 2022
                : 19
                : 3
                : 303-315
                Affiliations
                GRID grid.8241.f, ISNI 0000 0004 0397 2876, Cell Signalling and Immunology Division, , School of Life Sciences, University of Dundee, ; Dundee, DD1 5EH UK
                Author information
                http://orcid.org/0000-0001-8823-9718
                Article
                792
                10.1038/s41423-021-00792-8
                8891282
                34983947
                cb9d4128-11d9-4056-a6e4-9a73c834dd5b
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 July 2021
                : 24 September 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/100004440, Wellcome Trust (Wellcome);
                Award ID: 205023/Z/16/Z
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000925, Department of Health | National Health and Medical Research Council (NHMRC);
                Award ID: APP1120748
                Award Recipient :
                Categories
                Review Article
                Custom metadata
                © The Author(s), under exclusive licence to CSI and USTC 2022

                Immunology
                t lymphocyte,protein translation,proteomics,immunometabolism,protein degradation,t cells,tor signalling,proteolysis,lymphocyte activation,cell growth

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