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Molecular Cell Aug 2018The billions of proteins inside a eukaryotic cell are organized among dozens of sub-cellular compartments, within which they are further organized into protein... (Review)
Review
The billions of proteins inside a eukaryotic cell are organized among dozens of sub-cellular compartments, within which they are further organized into protein complexes. The maintenance of both levels of organization is crucial for normal cellular function. Newly made proteins that fail to be segregated to the correct compartment or assembled into the appropriate complex are defined as orphans. In this review, we discuss the challenges faced by a cell of minimizing orphaned proteins, the quality control systems that recognize orphans, and the consequences of excess orphans for protein homeostasis and disease.
Topics: Protein Biosynthesis; Protein Transport; Proteins; Proteolysis; Proteostasis
PubMed: 30075143
DOI: 10.1016/j.molcel.2018.07.001 -
Cold Spring Harbor Perspectives in... Dec 2018More than 40 different neurological diseases are caused by microsatellite repeat expansions that locate within translated or untranslated gene regions, including 5' and... (Review)
Review
More than 40 different neurological diseases are caused by microsatellite repeat expansions that locate within translated or untranslated gene regions, including 5' and 3' untranslated regions (UTRs), introns, and protein-coding regions. Expansion mutations are transcribed bidirectionally and have been shown to give rise to proteins, which are synthesized from three reading frames in the absence of an AUG initiation codon through a novel process called repeat-associated non-ATG (RAN) translation. RAN proteins, which were first described in spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1), have now been reported in a growing list of microsatellite expansion diseases. This article reviews what is currently known about RAN proteins in microsatellite expansion diseases and experiments that provide clues on how RAN translation is regulated.
Topics: Central Nervous System Diseases; Genetic Predisposition to Disease; Humans; Microsatellite Repeats; Protein Biosynthesis
PubMed: 29891563
DOI: 10.1101/cshperspect.a033019 -
Seminars in Cell & Developmental Biology Dec 2018The transition from oocyte to embryo marks the onset of development. This process requires complex regulation to link developmental signals with profound changes in mRNA... (Review)
Review
The transition from oocyte to embryo marks the onset of development. This process requires complex regulation to link developmental signals with profound changes in mRNA translation, cell cycle control, and metabolism. This control is beginning to be understood for most organisms, and research in the fruit fly Drosophila melanogaster has generated new insights. Recent findings have increased our understanding of the roles played by hormone and Ca signaling events as well as metabolic remodeling crucial for this transition. Specialized features of the structure and assembly of the meiotic spindle have been identified. The changes in protein levels, mRNA translation, and polyadenylation that occur as the oocyte becomes an embryo have been identified together with key aspects of their regulation. Here we highlight these important developments and the insights they provide on the intricate regulation of this dramatic transition.
Topics: Animals; Drosophila; Embryo, Mammalian; Embryonic Development; Humans; Meiosis; Oocytes; Oogenesis; Protein Biosynthesis
PubMed: 29448071
DOI: 10.1016/j.semcdb.2018.02.019 -
Genomics Jan 2021Deregulation of protein synthesis may be involved in multiple aspects of cancer, such as gene expression, signal transduction and drive specific cell biological... (Review)
Review
Deregulation of protein synthesis may be involved in multiple aspects of cancer, such as gene expression, signal transduction and drive specific cell biological responses, resulting in promoting cancer growth, invasion and metastasis. Study the molecular mechanisms about translational control may help us to find more effective anti-cancer drugs and develop novel therapeutic opportunities. Recently, the researchers had focused on targeting translational machinery to overcome cancer, and various small molecular inhibitors targeting translation factors or pathways have been tested in clinical trials and exhibited improving outcomes in several cancer types. There is no doubt that an insight into the class of translation regulation protein would provide new target for pharmacologic intervention and further provide opportunities to develop novel anti-tumor therapeutic interventions. In this review, we summarized the developments of translational control in cancer survival and progression et al, and highlighted the therapeutic approach targeted translation regulation to overcome the cancer.
Topics: Animals; Antineoplastic Agents; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Protein Biosynthesis; Ribosomal Proteins
PubMed: 33189778
DOI: 10.1016/j.ygeno.2020.11.011 -
Aging Dec 2018Aging is characterized by the accumulation of damage and other deleterious changes, leading to the loss of functionality and fitness. Age-related changes occur at most... (Review)
Review
Aging is characterized by the accumulation of damage and other deleterious changes, leading to the loss of functionality and fitness. Age-related changes occur at most levels of organization of a living organism (molecular, organellar, cellular, tissue and organ). However, protein synthesis is a major biological process, and thus understanding how it changes with age is of paramount importance. Here, we discuss the relationships between lifespan, aging, protein synthesis and translational control, and expand this analysis to the various aspects of proteome behavior in organisms with age. Characterizing the consequences of changes in protein synthesis and translation fidelity, and determining whether altered translation is pathological or adaptive is necessary for understanding the aging process, as well as for developing approaches to target dysfunction in translation as a strategy for extending lifespan.
Topics: Aging; Gene Expression Regulation; Humans; Protein Biosynthesis; Proteome
PubMed: 30562164
DOI: 10.18632/aging.101721 -
Cold Spring Harbor Perspectives in... Jul 2019The translation of messenger RNAs (mRNAs) into proteins is a key event in the regulation of gene expression. This is especially true in the cancer setting, as many... (Review)
Review
The translation of messenger RNAs (mRNAs) into proteins is a key event in the regulation of gene expression. This is especially true in the cancer setting, as many oncogenes and transforming events are regulated at this level. Cancer-promoting factors that are translationally regulated include cyclins, antiapoptotic factors, proangiogenic factors, regulators of cell metabolism, prometastatic factors, immune modulators, and proteins involved in DNA repair. This review discusses the diverse means by which cancer cells deregulate and reprogram translation, and the resulting oncogenic impacts, providing insights into the complexity of translational control in cancer and its targeting for cancer therapy.
Topics: Animals; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Protein Biosynthesis; RNA, Messenger
PubMed: 29959193
DOI: 10.1101/cshperspect.a032896 -
Immunology Dec 2018Formation of supramolecular assemblies appears to be a general mechanism in immune signalling pathways. These supramolecular assemblies appear to form through a... (Review)
Review
Formation of supramolecular assemblies appears to be a general mechanism in immune signalling pathways. These supramolecular assemblies appear to form through a nucleated polymerization mechanism. This review examines selected immune signalling pathways that involve supramolecular assemblies, describes the concepts of protein polymerization, and discusses how those concepts of protein polymerization implicate new elegant ways for signal amplification, setting threshold and noise reduction in these pathways.
Topics: Cytokines; Humans; Inflammasomes; Protein Biosynthesis; Protein Multimerization; Receptors, Cell Surface; Signal Transduction
PubMed: 30144032
DOI: 10.1111/imm.12995 -
Seminars in Cell & Developmental Biology Jul 2015Amino acids have a dual role in cellular metabolism, as they are both the building blocks for protein synthesis and intermediate metabolites which fuel other... (Review)
Review
Amino acids have a dual role in cellular metabolism, as they are both the building blocks for protein synthesis and intermediate metabolites which fuel other biosynthetic reactions. Recent work has demonstrated that deregulation of both arms of amino acid management are common alterations seen in cancer. Among the most highly consumed nutrients by cancer cells are the amino acids glutamine and serine, and the biosynthetic pathways that metabolize them are required in various cancer subtypes and the object of current efforts to target cancer metabolism. Also altered in cancer are components of the machinery which sense amino acid sufficiency, nucleated by the mechanistic target of rapamycin (mTOR), a key regulator of cell growth via modulation of key processes including protein synthesis and autophagy. The precise ways in which altered amino acid management supports cellular transformation remain mostly elusive, and a fuller mechanistic understanding of these processes will be important for efforts to exploit such alterations for cancer therapy.
Topics: Citric Acid Cycle; Glutamine; Humans; Neoplasms; Protein Biosynthesis; Serine; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 26277542
DOI: 10.1016/j.semcdb.2015.08.002 -
Nature Reviews. Molecular Cell Biology Aug 2018During protein synthesis, ribosomes encounter many roadblocks, the outcomes of which are largely determined by substrate availability, amino acid features and reaction... (Review)
Review
During protein synthesis, ribosomes encounter many roadblocks, the outcomes of which are largely determined by substrate availability, amino acid features and reaction kinetics. Prolonged ribosome stalling is likely to be resolved by ribosome rescue or quality control pathways, whereas shorter stalling is likely to be resolved by ongoing productive translation. How ribosome function is affected by such hindrances can therefore have a profound impact on the translational output (yield) of a particular mRNA. In this Review, we focus on these roadblocks and the resumption of normal translation elongation rather than on alternative fates wherein the stalled ribosome triggers degradation of the mRNA and the incomplete protein product. We discuss the fundamental stages of the translation process in eukaryotes, from elongation through ribosome recycling, with particular attention to recent discoveries of the complexity of the genetic code and regulatory elements that control gene expression, including ribosome stalling during elongation, the role of mRNA context in translation termination and mechanisms of ribosome rescue that resemble recycling.
Topics: Animals; Eukaryota; Gene Expression; Gene Expression Regulation; Protein Biosynthesis; RNA, Messenger; Ribosomes
PubMed: 29760421
DOI: 10.1038/s41580-018-0011-4 -
The Journal of Biological Chemistry Nov 2015Emerging evidence indicates that protein synthesis and degradation are necessary for the remodeling of synapses. These two processes govern cellular protein turnover,... (Review)
Review
Emerging evidence indicates that protein synthesis and degradation are necessary for the remodeling of synapses. These two processes govern cellular protein turnover, are tightly regulated, and are modulated by neuronal activity in time and space. The anisotropic anatomy of the neurons presents a challenge for the study of protein turnover, but the understanding of protein turnover in neurons and its modulation in response to activity can help us to unravel the fine-tuned changes that occur at synapses in response to activity. Here we review the key experimental evidence demonstrating the role of protein synthesis and degradation in synaptic plasticity, as well as the turnover rates of specific neuronal proteins.
Topics: Animals; Humans; Nerve Tissue Proteins; Neurons; Protein Biosynthesis; Proteolysis; Synapses
PubMed: 26453306
DOI: 10.1074/jbc.R115.657130