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Amino Acids Dec 2021Proline is a non-essential amino acid with key roles in protein structure/function and maintenance of cellular redox homeostasis. It is available from dietary sources,... (Review)
Review
Proline is a non-essential amino acid with key roles in protein structure/function and maintenance of cellular redox homeostasis. It is available from dietary sources, generated de novo within cells, and released from protein structures; a noteworthy source being collagen. Its catabolism within cells can generate ATP and reactive oxygen species (ROS). Recent findings suggest that proline biosynthesis and catabolism are essential processes in disease; not only due to the role in new protein synthesis as part of pathogenic processes but also due to the impact of proline metabolism on the wider metabolic network through its significant role in redox homeostasis. This is particularly clear in cancer proliferation and metastatic outgrowth. Nevertheless, the precise identity of the drivers of cellular proline catabolism and biosynthesis, and the overall cost of maintaining appropriate balance is not currently known. In this review, we explore the major drivers of proline availability and consumption at a local and systemic level with a focus on cancer. Unraveling the main factors influencing proline metabolism in normal physiology and disease will shed light on new effective treatment strategies.
Topics: Animals; Homeostasis; Humans; Neoplasms; Oxidation-Reduction; Proline; Protein Biosynthesis; Reactive Oxygen Species
PubMed: 34291343
DOI: 10.1007/s00726-021-03051-2 -
Current Opinion in Genetics &... Feb 2018The processes by which the canonical protein synthesis machinery is modified by environmental stresses to allow healthy cells to respond to external conditions to... (Review)
Review
The processes by which the canonical protein synthesis machinery is modified by environmental stresses to allow healthy cells to respond to external conditions to maintain homeostasis, are frequently hijacked by tumour cells to enhance their survival. Two major stress response pathways that play a major role in this regard are the unfolded protein response (UPR) and the DNA damage response (DDR). Recent data have shown that key proteins which coordinate post-transcriptional control, and which are regulated by signalling through the UPR and DDR, are upregulated in cancers and that targeting these proteins/pathways will provide new therapeutic avenues for cancer treatments.
Topics: Animals; DNA Repair; Gene Expression Regulation; Humans; Neoplasms; Protein Biosynthesis; Unfolded Protein Response
PubMed: 29100210
DOI: 10.1016/j.gde.2017.10.006 -
Frontiers in Bioscience (Landmark... Jan 2015The metabolic roles for L-leucine, an essential branched-chain amino acid (BCAA), go far beyond serving exclusively as a building block for de novo protein synthesis.... (Review)
Review
The metabolic roles for L-leucine, an essential branched-chain amino acid (BCAA), go far beyond serving exclusively as a building block for de novo protein synthesis. Growing evidence shows that leucine regulates protein and lipid metabolism in animals. Specifically, leucine activates the mammalian target of rapamycin (mTOR) signaling pathway, including the 70 kDa ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1) to stimulate protein synthesis in skeletal muscle and adipose tissue and to promote mitochondrial biogenesis, resulting in enhanced cellular respiration and energy partitioning. Activation of cellular energy metabolism favors fatty acid oxidation to CO2 and water in adipocytes, lean tissue gain in young animals, and alleviation of muscle protein loss in aging adults, lactating mammals, and food-deprived subjects. As a functional amino acid, leucine holds great promise to enhance the growth, efficiency of food utilization, and health of animals and humans.
Topics: Adipose Tissue; Animals; Energy Metabolism; Humans; Leucine; Muscle, Skeletal; Protein Biosynthesis
PubMed: 25553480
DOI: 10.2741/4338 -
Current Opinion in Plant Biology Oct 2023Transposons are mobile DNA sequences that can move within the genome and integrate in new genomic locations. They are widespread in eukaryotes and prokaryotes and can... (Review)
Review
Transposons are mobile DNA sequences that can move within the genome and integrate in new genomic locations. They are widespread in eukaryotes and prokaryotes and can influence gene expression when landing within or nearby a gene. Although transposon-induced regulation of gene expression at the transcriptional level has been extensively studied, there has been less focus on regulation at the post-transcriptional and translational levels. Recent studies in maize (Zea mays) and other plant species suggest that transposon insertions can affect RNA processing, RNA stability, protein translation and protein stability. We will describe the diverse mechanisms by which transposons can influence gene expression at the post-transcriptional and translational levels, and discuss the interactions between these mechanisms.
Topics: Genes, Plant; Genomics; Protein Biosynthesis; RNA Stability; Zea mays
PubMed: 37619514
DOI: 10.1016/j.pbi.2023.102438 -
The Journal of General Physiology Jul 1966Outline of the steps in protein synthesis. Nature of the genetic code. The use of synthetic oligo- and polynucleotides in deciphering the code. Structure of the code:... (Review)
Review
Outline of the steps in protein synthesis. Nature of the genetic code. The use of synthetic oligo- and polynucleotides in deciphering the code. Structure of the code: relatedness of synonym codons. The wobble hypothesis. Chain initiation and N-formyl-methionine. Chain termination and nonsense codons. Mistakes in translation: ambiguity in vitro. Suppressor mutations resulting in ambiguity. Limitations in the universality of the code. Attempts to determine the particular codons used by a species. Mechanisms of suppression, caused by (a) abnormal aminoacyl-tRNA, (b) ribosomal malfunction. Effect of streptomycin. The problem of "reading" a nucleic acid template. Different ribosomal mutants and DNA polymerase mutants might cause different mistakes. The possibility of involvement of allosteric proteins in template reading.
Topics: Genetic Code; Protein Biosynthesis
PubMed: 5338560
DOI: 10.1085/jgp.49.6.305 -
International Journal of Molecular... Jan 2022Among the 20 amino acids needed for protein synthesis, Tryptophan (Trp) is an aromatic amino acid fundamental not only for the synthesis of the major components of...
Among the 20 amino acids needed for protein synthesis, Tryptophan (Trp) is an aromatic amino acid fundamental not only for the synthesis of the major components of living cells (namely, the proteins), but also for the maintenance of cellular homeostasis [...].
Topics: Disease Susceptibility; Homeostasis; Humans; Metabolic Networks and Pathways; Protein Biosynthesis; Tryptophan
PubMed: 35054973
DOI: 10.3390/ijms23020787 -
Cell Systems Feb 2020How do cells maintain relative proportions of protein complex components? Advances in quantitative, genome-wide measurements have begun to shed light onto the roles of... (Review)
Review
How do cells maintain relative proportions of protein complex components? Advances in quantitative, genome-wide measurements have begun to shed light onto the roles of protein synthesis and degradation in establishing the precise proportions in living cells: on the one hand, ribosome profiling studies indicate that proteins are already produced in the correct relative proportions. On the other hand, proteomic studies found that many complexes contain subunits that are made in excess and subsequently degraded. Here, we discuss these seemingly contradictory findings, emerging principles, and remaining open questions. We conclude that establishing precise protein levels involves both coordinated synthesis and post-translational fine-tuning via protein degradation.
Topics: Protein Biosynthesis; Proteins
PubMed: 32105631
DOI: 10.1016/j.cels.2020.01.004 -
Cold Spring Harbor Perspectives in... Jun 2019The many steps of gene expression, from the transcription of a gene to the production of its protein product, are well understood. Yet, transcriptional regulation has... (Review)
Review
The many steps of gene expression, from the transcription of a gene to the production of its protein product, are well understood. Yet, transcriptional regulation has been the focal point for the study of gene expression during development. However, quantitative studies reveal that messenger RNA (mRNA) levels are not necessarily good predictors of the respective proteins' levels in a cell. This discrepancy is, at least in part, the result of developmentally regulated, translational mechanisms that control the spatiotemporal regulation of gene expression. In this review, we focus on translational regulatory mechanisms mediating global transitions in gene expression: the shift from the maternal to the embryonic developmental program in the early embryo and the switch from the self-renewal of stem cells to differentiation in the adult.
Topics: Animals; Cell Differentiation; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Protein Biosynthesis; Protein Processing, Post-Translational; RNA, Messenger
PubMed: 30082467
DOI: 10.1101/cshperspect.a032987 -
Journal of Applied Physiology... Nov 2015
Topics: Animals; Congresses as Topic; Humans; Hypoxia; Protein Biosynthesis; Translational Research, Biomedical
PubMed: 26338459
DOI: 10.1152/japplphysiol.00745.2015 -
Wiley Interdisciplinary Reviews. RNA Jan 2017Quality control processes are widespread and play essential roles in detecting defective molecules and removing them in order to maintain organismal fitness. Aberrant... (Review)
Review
Quality control processes are widespread and play essential roles in detecting defective molecules and removing them in order to maintain organismal fitness. Aberrant messenger RNA (mRNA) molecules, unless properly managed, pose a significant hurdle to cellular proteostasis. Often mRNAs harbor premature stop codons, possess structures that present a block to the translational machinery, or lack stop codons entirely. In eukaryotes, the three cytoplasmic mRNA-surveillance processes, nonsense-mediated decay (NMD), no-go decay (NGD), and nonstop decay (NSD), evolved to cope with these aberrant mRNAs, respectively. Nonstop mRNAs and mRNAs that inhibit translation elongation are especially problematic as they sequester valuable ribosomes from the translating ribosome pool. As a result, in addition to RNA degradation, NSD and NGD are intimately coupled to ribosome rescue in all domains of life. Furthermore, protein products produced from all three classes of defective mRNAs are more likely to malfunction. It is not surprising then that these truncated nascent protein products are subject to degradation. Over the past few years, many studies have begun to document a central role for the ribosome in initiating the RNA and protein quality control processes. The ribosome appears to be responsible for recognizing the target mRNAs as well as for recruiting the factors required to carry out the processes of ribosome rescue and nascent protein decay. WIREs RNA 2017, 8:e1366. doi: 10.1002/wrna.1366 For further resources related to this article, please visit the WIREs website.
Topics: Animals; Humans; Peptide Chain Elongation, Translational; Peptide Chain Termination, Translational; Protein Biosynthesis; RNA, Messenger; Ribosomes
PubMed: 27193249
DOI: 10.1002/wrna.1366