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Signal Transduction and Targeted Therapy Dec 2022Metabolic reprogramming is involved in the pathogenesis of not only cancers but also neurodegenerative diseases, cardiovascular diseases, and infectious diseases. With... (Review)
Review
Metabolic reprogramming is involved in the pathogenesis of not only cancers but also neurodegenerative diseases, cardiovascular diseases, and infectious diseases. With the progress of metabonomics and proteomics, metabolites have been found to affect protein acylations through providing acyl groups or changing the activities of acyltransferases or deacylases. Reciprocally, protein acylation is involved in key cellular processes relevant to physiology and diseases, such as protein stability, protein subcellular localization, enzyme activity, transcriptional activity, protein-protein interactions and protein-DNA interactions. Herein, we summarize the functional diversity and mechanisms of eight kinds of nonhistone protein acylations in the physiological processes and progression of several diseases. We also highlight the recent progress in the development of inhibitors for acyltransferase, deacylase, and acylation reader proteins for their potential applications in drug discovery.
Topics: Acyltransferases; Acylation; Proteins; Protein Processing, Post-Translational
PubMed: 36577755
DOI: 10.1038/s41392-022-01245-y -
Journal of Experimental & Clinical... Apr 2022Metabolites are intermediate products of cellular metabolism catalysed by various enzymes. Metabolic remodelling, as a biochemical fingerprint of cancer cells, causes... (Review)
Review
Metabolites are intermediate products of cellular metabolism catalysed by various enzymes. Metabolic remodelling, as a biochemical fingerprint of cancer cells, causes abnormal metabolite accumulation. These metabolites mainly generate energy or serve as signal transduction mediators via noncovalent interactions. After the development of highly sensitive mass spectrometry technology, various metabolites were shown to covalently modify proteins via forms of lysine acylation, including lysine acetylation, crotonylation, lactylation, succinylation, propionylation, butyrylation, malonylation, glutarylation, 2-hydroxyisobutyrylation and β-hydroxybutyrylation. These modifications can regulate gene expression and intracellular signalling pathways, highlighting the extensive roles of metabolites. Lysine acetylation is not discussed in detail in this review since it has been broadly investigated. We focus on the nine aforementioned novel lysine acylations beyond acetylation, which can be classified into two categories: histone acylations and nonhistone acylations. We summarize the characteristics and common functions of these acylation types and, most importantly, provide a glimpse into their fine-tuned control of tumorigenesis and potential value in tumour diagnosis, monitoring and therapy.
Topics: Acetylation; Acylation; Carcinogenesis; Histones; Humans; Lysine; Protein Processing, Post-Translational
PubMed: 35428309
DOI: 10.1186/s13046-022-02338-w -
Cell Mar 2023A generalizable strategy with programmable site specificity for in situ profiling of histone modifications on unperturbed chromatin remains highly desirable but...
A generalizable strategy with programmable site specificity for in situ profiling of histone modifications on unperturbed chromatin remains highly desirable but challenging. We herein developed a single-site-resolved multi-omics (SiTomics) strategy for systematic mapping of dynamic modifications and subsequent profiling of chromatinized proteome and genome defined by specific chromatin acylations in living cells. By leveraging the genetic code expansion strategy, our SiTomics toolkit revealed distinct crotonylation (e.g., H3K56cr) and β-hydroxybutyrylation (e.g., H3K56bhb) upon short chain fatty acids stimulation and established linkages for chromatin acylation mark-defined proteome, genome, and functions. This led to the identification of GLYR1 as a distinct interacting protein in modulating H3K56cr's gene body localization as well as the discovery of an elevated super-enhancer repertoire underlying bhb-mediated chromatin modulations. SiTomics offers a platform technology for elucidating the "metabolites-modification-regulation" axis, which is widely applicable for multi-omics profiling and functional dissection of modifications beyond acylations and proteins beyond histones.
Topics: Acylation; Chromatin; Chromosome Mapping; Histones; Proteome; Cell Survival
PubMed: 36868209
DOI: 10.1016/j.cell.2023.02.007 -
International Journal of Molecular... Jan 2019Lipid modification is an important post-translational modification. S-acylation is unique among lipid modifications, as it is reversible and has thus attracted much... (Review)
Review
Lipid modification is an important post-translational modification. S-acylation is unique among lipid modifications, as it is reversible and has thus attracted much attention. We summarize some proteins that have been shown experimentally to be S-acylated in plants. Two of these S-acylated proteins have been matched to the S-acyl transferase. More importantly, the first protein thioesterase with de-S-acylation activity has been identified in plants. This review shows that S-acylation is important for a variety of different functions in plants and that there are many unexplored aspects of S-acylation in plants.
Topics: Acylation; Lipid Metabolism; Models, Biological; Monomeric GTP-Binding Proteins; Plant Proteins; Protein Processing, Post-Translational; Transcription Factors
PubMed: 30699892
DOI: 10.3390/ijms20030560 -
Cell Chemical Biology Jul 2022A critical step in repurposing the cellular translation machinery for the synthesis of polymeric products is the acylation of transfer RNA (tRNA) with unnatural... (Review)
Review
A critical step in repurposing the cellular translation machinery for the synthesis of polymeric products is the acylation of transfer RNA (tRNA) with unnatural monomers. Toward this goal, flexizymes, ribozymes capable of aminoacylation, have emerged as a uniquely adept tool for charging tRNA with ever increasingly diverse substrates. In this review, we present a library of monomer substrates that have been tested for tRNA acylation with the flexizyme system. From this mile-high view, we provide insights for understanding the chemical factors that influence flexizyme-mediated tRNA acylation. We conclude that flexizymes are primitive esterification catalysts that display a modest binding affinity to the monomer's aromatic recognition element. Together, these robust, yet flexible, flexizyme systems provide researchers with unprecedented access for preparing unnatural acyl-tRNA and the opportunity to repurpose the translation machinery for the synthesis of novel biologically derived structures beyond native proteins and peptides.
Topics: Acylation; Catalysis; Peptides; RNA, Catalytic; RNA, Transfer; Transfer RNA Aminoacylation
PubMed: 35413283
DOI: 10.1016/j.chembiol.2022.03.012 -
Journal of Cell Science Jun 2024An important mechanism of gene expression regulation is the epigenetic modification of histones. The cofactors and substrates for these modifications are often... (Review)
Review
An important mechanism of gene expression regulation is the epigenetic modification of histones. The cofactors and substrates for these modifications are often intermediary metabolites, and it is becoming increasingly clear that the metabolic and nutritional state of cells can influence these marks. These connections between the balance of metabolites, histone modifications and downstream transcriptional changes comprise a metabolic signaling program that can enable cells to adapt to changes in nutrient availability. Beyond acetylation, there is evidence now that histones can be modified by other acyl groups. In this Cell Science at a Glance article and the accompanying poster, we focus on these histone acylation modifications and provide an overview of the players that govern these acylations and their connections with metabolism.
Topics: Animals; Humans; Acylation; Epigenesis, Genetic; Histones; Protein Processing, Post-Translational
PubMed: 38842578
DOI: 10.1242/jcs.261250 -
Journal of Proteome Research Jan 2021Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization,... (Review)
Review
Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization, activity, stability, and complex formation. The deregulation of protein -acylation contributes to many diseases such as cancer and neurodegenerative disorders. The past decade has witnessed substantial progress in proteomic analysis of protein -acylation, which significantly advanced our understanding of -acylation biology. In this review, we summarized the techniques for the enrichment of -acylated proteins or peptides, critically reviewed proteomic studies of protein -acylation at eight different levels, and proposed major challenges for the -acylproteomics field. In summary, proteome-scale analysis of protein -acylation comes of age and will play increasingly important roles in discovering new disease mechanisms, biomarkers, and therapeutic targets.
Topics: Acylation; Lipoylation; Protein S; Proteome; Proteomics
PubMed: 33253586
DOI: 10.1021/acs.jproteome.0c00409 -
Clinical Science (London, England :... Mar 2020Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Metabolic dysfunction is a fundamental core mechanism underlying CVDs.... (Review)
Review
Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Metabolic dysfunction is a fundamental core mechanism underlying CVDs. Previous studies generally focused on the roles of long-chain fatty acids (LCFAs) in CVDs. However, a growing body of study has implied that short-chain fatty acids (SCFAs: namely propionate, malonate, butyrate, 2-hydroxyisobutyrate (2-HIBA), β-hydroxybutyrate, crotonate, succinate, and glutarate) and their cognate acylations (propionylation, malonylation, butyrylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, crotonylation, succinylation, and glutarylation) participate in CVDs. Here, we attempt to provide an overview landscape of the metabolic pattern of SCFAs in CVDs. Especially, we would focus on the SCFAs and newly identified acylations and their roles in CVDs, including atherosclerosis, hypertension, and heart failure.
Topics: Acetylation; Animals; Cardiovascular Diseases; Fatty Acids, Volatile; Humans
PubMed: 32219347
DOI: 10.1042/CS20200128 -
Chemistry (Weinheim An Der Bergstrasse,... Sep 2022Acylated nucleoside analogues play an important role in medicinal chemistry and are extremely useful precursors to various other nucleoside analogues. However,...
Acylated nucleoside analogues play an important role in medicinal chemistry and are extremely useful precursors to various other nucleoside analogues. However, chemoselective acylation of nucleosides usually requires several protection and deprotection steps due to the competing nucleophilicity of hydroxy and amino groups. In contrast, direct protecting-group-free chemoselective acylation of nucleosides is a preferred strategy due to lower cost and fewer overall synthetic steps. Herein, a simple and efficient chemoselective acylation of nucleosides and nucleotides under mild reaction conditions, giving either O- or N-acylated products respectively with excellent chemoselectivity is reported.
Topics: Acylation; Chemistry, Pharmaceutical; Nucleosides; Nucleotides
PubMed: 35730928
DOI: 10.1002/chem.202201661 -
Critical Reviews in Food Science and... 2023Anthocyanins are naturally occurring bioactive compounds found mainly in fruits, vegetables, and grains. They are usually extracted due to their biological properties... (Review)
Review
Anthocyanins are naturally occurring bioactive compounds found mainly in fruits, vegetables, and grains. They are usually extracted due to their biological properties and great potential for technological applications. These compounds have characteristic pH-dependent colorations that are natural dyes since they come in different colors. However, they are susceptible to processing conditions, remarkably light, temperature, and oxygen. The acylated anthocyanins showed better stability characteristics, and therefore, an acylation process of these compounds could improve their applications. The enzymatic acylation was effective and showed promising results. The current review provides an overview of the works that performed enzymatic acylation of anthocyanins and studies on the stability, antioxidant activity, and lipophilicity. In general, enzymatically acylated anthocyanins showed better stability to light and temperature than non-acylated compounds. In addition, they were liposoluble, a characteristic that allows their addition to products with lipid matrices. The results showed that these compounds formed by enzymatic acylation have perspectives of application mainly as natural colorants in food products. Therefore, the enzymatic acylation of anthocyanins appears viable to increase the industrial applicability of anthocyanins. There are still some gaps to be filled in process optimization, the reuse of enzymes, and toxicity analysis of the acylated compounds formed.
Topics: Anthocyanins; Antioxidants; Temperature; Acylation; Fruit
PubMed: 35191785
DOI: 10.1080/10408398.2022.2041541