•The interaction between protein phosphorylation and acetylation was studied.•TSA and NAM inhibited the deacetylation of MHC and actin.•Actomyosin dissociation was inhibited by MHC and actin protein ...acetylation.•Phosphorylation of MHC and actin were inhibited by its acetylation in vitro.•Total energy in acetylated actomyosin was lower than that in unacetylated actomyosin.
This study aimed to assess the effects of acetylation levels on actomyosin disassociation and phosphorylation of lamb during incubation at 4 °C. Samples of whole proteins from lamb longissimus thoracis muscles were prepared and assigned into three treatments (high, middle and low acetylation groups). The results showed that deacetylation of myosin heavy chain and actin was inhibited by lysine deacetylase inhibitor trichostatin A and nicotinamide in this study. Phosphorylation levels of myosin heavy chain and actin were inhibited by their acetylation during incubation in vitro. Actomyosin disassociation degree in high acetylation group was significantly lower than that in middle and low acetylation groups (P < 0.05). The ATPase activity in high acetylation group was significantly higher than that in middle and low acetylation groups (P < 0.05). In conclusion, acetylation of myosin heavy chain and actin inhibited actomyosin dissociation by inhibiting their phosphorylation at 4 °C in vitro.
•Calcium bound and covalently linked pectin analyzed in 26 food waste streams.•Uronic acid content, neutral sugars, acetylation and methylation degree determined.•Very wide diversity of pectin ...structures among vegetal food waste materials.•First wide database of pectin content and characterization.
In the present paper, 26 food waste streams were selected according to their exploitation potential and investigated in terms of pectin content. The isolated pectin, subdivided into calcium bound and alkaline extractable pectin, was fully characterized in terms of uronic acid and other sugar composition, methylation and acetylation degree. It was shown that many waste streams can be a valuable source of pectin, but also that pectin structures present a huge structural diversity, resulting in a broad range of pectin structures. These can have different physicochemical and biological properties, which are useful in a wide range of applications. Even if the data could not cover all the possible batch by batch and country variabilities, to date this represents the most complete pectin characterization from food waste streams ever reported in the literature with a homogeneous methodology.
Recent studies of N-terminal acetylation have identified new N-terminal acetyltransferases (NATs) and expanded the known functions of these enzymes beyond their roles as ribosome-associated ...co-translational modifiers. For instance, the identification of Golgi- and chloroplast-associated NATs shows that acetylation of N termini also happens post-translationally. In addition, we now appreciate that some NATs are highly specific; for example, a dedicated NAT responsible for post-translational N-terminal acetylation of actin was recently revealed. Other studies have extended NAT function beyond Nt acetylation, including functions as lysine acetyltransferases (KATs) and non-catalytic roles. Finally, emerging studies emphasize the physiological relevance of N-terminal acetylation, including roles in calorie-restriction-induced longevity and pathological α-synuclein aggregation in Parkinson’s disease. Combined, the NATs rise as multifunctional proteins, and N-terminal acetylation is gaining recognition as a major cellular regulator.
N-terminal acetylation, long considered a co-translational and static modification, recently stepped into the post-translational world, and several reports now suggest regulation and crosstalk with other modifications as well as moonlighting functions. Aksnes et al. review novel functions of N-terminal acetyltransferases, including the most recently described Nt acetylation of actin.
Mammals possess an intricate regulatory system for controlling flux through fuel utilization pathways in response to the dietary availability of particular macronutrients. Under fasting conditions, ...for instance, mammals initiate a whole body metabolic response that limits glucose utilization and favors fatty acid oxidation. Understanding the underlying mechanisms by which this process occurs will facilitate the development of new treatments for metabolic disorders such as type II diabetes and obesity. One of the recently identified components of the signal transduction pathway involved in metabolic reprogramming is PGC-1α. This transcriptional coactivator is able to coordinate the expression of a wide array of genes involved in glucose and fatty acid metabolism. The nutrient-mediated control of PGC-1α activity is tightly correlated with its acetylation state. In this review, we evaluate how the nutrient regulation of PGC-1α activity squares with the regulation of its acetylation state by the deacetylase Sirt1 and the acetyltransferase GCN5. We also propose an outline of additional experimental directives that will help to shed additional light on this very powerful transcriptional coactivator.
Currently, resistance to trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor, has become one major obstacle for improving the clinical outcome of patients with advanced HER2+ ...breast cancer. While cell behaviour can be modulated by long non‐coding RNAs (lncRNAs), the contributions of lncRNAs in progression and trastuzumab resistance of breast cancer are largely unknown. To this end, the involvement and regulatory functions of lncRNA SNHG14 in human breast cancer were investigated. RT‐qPCR assay showed that SNHG14 was up‐regulated in breast cancer tissues and associated with trastuzumab response. Gain‐ and loss‐of‐function experiments revealed that overexpression of SNHG14 promotes cell proliferation, invasion and trastuzumab resistance, whereas knockdown of SNHG14 showed an opposite effect. PABPC1 gene was identified as a downstream target of SNHG14, and PABPC1 mediates the SNHG14‐induced oncogenic effects. More importantly, ChIP assays demonstrated that lncRNA SNHG14 may induce PABPC1 expression through modulating H3K27 acetylation in the promoter of PABPC1 gene, thus resulting in the activation of Nrf2 signalling pathway. These data suggest that lncRNA SNHG14 promotes breast cancer tumorigenesis and trastuzumab resistance through regulating PABPC1 expression through H3K27 acetylation. Therefore, SNHG14 may serve as a novel diagnostic and therapeutic target for breast cancer patients.
Long-term manganese exposure causes a neurodegenerative disorder referred to as manganese poisoning, but the mechanism remains unclear and no specific treatment is available. Oxidative stress is ...widely recognised as one of the main causes of manganese-induced neurotoxicity. In recent years, the role of histone acetylation in neurodegenerative diseases has been widely concerned. curcumin is a natural polyphenol compound extracted from the rhizome of turmeric and exhibits both antioxidant and neuroprotective properties. Therefore, we aimed to investigate whether and how curcumin protects against manganese-induced neurotoxicity from the perspective of histone acetylation, based on the reversibility of histone acetylation modification. In this study, rats were treated with or without curcumin and subjected to long-term manganese exposure. Results that treatment of manganese decreased the protein expression of H3K18 acetylation and H3K27 acetylation at the promoters of oxidative stress-related genes and inhibited the expression of these genes. Nevertheless, curcumin increased the H3K27 acetylation level at the manganese superoxide dismutase (SOD2) gene promoter and promoted the expression of SOD2 gene. Oxidative damage in the rat striatum as well as learning and memory dysfunction were ameliorated after curcumin treatment. Taken together, our results suggest that the regulation of oxidative stress by histone acetylation may be a key mechanism of manganese-induced neurotoxicity. In addition, curcumin ameliorates Mn-induced neurotoxicity may be due to alleviation of oxidative damage mediated by increased activation of H3K27 acetylation at the SOD2 gene promoter.
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•Down-acetylation levels of H3K27 and H3K18 may inhibit the expression of OSR genes.•Curcumin ameliorates Mn-induced neurotoxicity in rat.•Curcumin increases the expression of SOD2 gene by the up-acetylation level of H3K27.
Lysine acetylation of proteins is a major post-translational modification that plays an important regulatory role in almost every aspect of cells, both eukaryotes and prokaryotes. Vibrio ...parahemolyticus, a model marine bacterium, is a worldwide cause of bacterial seafood-borne illness. Here, we conducted the first lysine acetylome in this bacterium through a combination of highly sensitive immune-affinity purification and high-resolution LC–MS/MS. Overall, we identified 1413 lysine acetylation sites in 656 proteins, which account for 13.6% of the total proteins in the cells; this is the highest ratio of acetyl proteins that has so far been identified in bacteria. The bioinformatics analysis of the acetylome showed that the acetylated proteins are involved in a wide range of cellular functions and exhibit diverse subcellular localizations. More specifically, proteins related to protein biosynthesis and carbon metabolism are the preferential targets of lysine acetylation. Moreover, two types of acetylation motifs, a lysine or arginine at the +4/+5 positions and a tyrosine, histidine, or phenylalanine at the +1/+2 positions, were revealed from the analysis of the acetylome. Additionally, protein interaction network analysis demonstrates that a wide range of interactions are modulated by protein acetylation. This study provides a significant beginning for the in-depth exploration of the physiological role of lysine acetylation in V. parahemolyticus.
Toll-like receptor (TLR) activation induces inflammatory responses in macrophages by activating temporally defined transcriptional cascades. Whether concurrent changes in the cellular metabolism that ...occur upon TLR activation influence the quality of the transcriptional responses remains unknown. Here, we investigated how macrophages adopt their metabolism early after activation to regulate TLR-inducible gene induction. Shortly after TLR4 activation, macrophages increased glycolysis and tricarboxylic acid (TCA) cycle volume. Metabolic tracing studies revealed that TLR signaling redirected metabolic fluxes to generate acetyl-Coenzyme A (CoA) from glucose resulting in augmented histone acetylation. Signaling through the adaptor proteins MyD88 and TRIF resulted in activation of ATP-citrate lyase, which in turn facilitated the induction of distinct LPS-inducible gene sets. We postulate that metabolic licensing of histone acetylation provides another layer of control that serves to fine-tune transcriptional responses downstream of TLR activation. Our work highlights the potential of targeting the metabolic-epigenetic axis in inflammatory settings.
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•Macrophages adopt a transient metabolic state in response to TLR4 activation•MyD88 and TRIF synergistically facilitate signaling-driven changes in metabolism•Increases in glycolysis and ATP-citrate lyase activity foster histone acetylation•ATP-citrate lyase governs gene induction of a distinct LPS responsive gene set
TLR4 activation by LPS induces defined transcriptional cascades. Lauterbach et al. provide evidence that TLR activation induces a transient metabolic state that supports the transcriptional response. Mechanistically, they show that concerted increases in glycolytic flux and ATP-citrate lyase activity foster histone acetylation.
The aggregation of the protein α‐synuclein (AS) is critical to the pathogenesis of Parkinson's disease. Although generally described as an unstructured monomer, recent evidence suggests that the ...native form of AS may be an α‐helical tetramer which resists aggregation. Here, we show that N‐terminal acetylation in combination with a mild purification protocol results in an oligomeric form of AS with partial α‐helical structure. N‐terminal acetylation of AS could have important implications for both the native and pathological structures and functions of AS. Through our demonstration of a recombinant expression system, our results represent an important step toward biochemical and biophysical characterization of this potentially important form of AS.
Nɛ-Acetylation of lysine residues represents a pivotal post-translational modification used by both eukaryotes and prokaryotes to modulate diverse biological processes. Mycobacterium tuberculosis is ...the causative agent of tuberculosis, one of the most formidable public health threats. Many aspects of the biology of M. tuberculosis remain elusive, in particular the extent and function of Nɛ-lysine acetylation. With a combination of anti-acetyllysine antibody-based immunoaffinity enrichment with high-resolution mass spectrometry, we identified 1128 acetylation sites on 658 acetylated M. tuberculosis proteins. GO analysis of the acetylome showed that acetylated proteins are involved in the regulation of diverse cellular processes including metabolism and protein synthesis. Six types of acetylated peptide sequence motif were revealed from the acetylome. Twenty lysine-acetylated proteins showed homology with acetylated proteins previously identified from Escherichia coli, Salmonella enterica, Bacillus subtilis and Streptomyces roseosporus, with several acetylation sites highly conserved among four or five bacteria, suggesting that acetylated proteins are more conserved. Notably, several proteins including isocitrate lyase involved in the persistence, virulence and antibiotic resistance are acetylated, and site-directed mutagenesis of isocitrate lyase acetylation site to glutamine led to a decrease of the enzyme activity, indicating major roles of KAc in these proteins engaged cellular processes. Our data firstly provides a global survey of M. tuberculosis acetylation, and implicates extensive regulatory role of acetylation in this pathogen. This may serve as an important basis to address the roles of lysine acetylation in M. tuberculosis metabolism, persistence and virulence.
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