-
Eukaryotic Cell Dec 2014Cells sense and appropriately respond to the physical conditions and availability of nutrients in their environment. This sensing of the environment and consequent... (Review)
Review
Cells sense and appropriately respond to the physical conditions and availability of nutrients in their environment. This sensing of the environment and consequent cellular responses are orchestrated by a multitude of signaling pathways and typically involve changes in transcription and metabolism. Recent discoveries suggest that the signaling and transcription machineries are regulated by signals which are derived from metabolism and reflect the metabolic state of the cell. Acetyl coenzyme A (CoA) is a key metabolite that links metabolism with signaling, chromatin structure, and transcription. Acetyl-CoA is produced by glycolysis as well as other catabolic pathways and used as a substrate for the citric acid cycle and as a precursor in synthesis of fatty acids and steroids and in other anabolic pathways. This central position in metabolism endows acetyl-CoA with an important regulatory role. Acetyl-CoA serves as a substrate for lysine acetyltransferases (KATs), which catalyze the transfer of acetyl groups to the epsilon-amino groups of lysines in histones and many other proteins. Fluctuations in the concentration of acetyl-CoA, reflecting the metabolic state of the cell, are translated into dynamic protein acetylations that regulate a variety of cell functions, including transcription, replication, DNA repair, cell cycle progression, and aging. This review highlights the synthesis and homeostasis of acetyl-CoA and the regulation of transcriptional and signaling machineries in yeast by acetylation.
Topics: Acetyl Coenzyme A; Acetylation; Animals; Homeostasis; Humans; Protein Processing, Post-Translational; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 25326522
DOI: 10.1128/EC.00189-14 -
Methods in Molecular Biology (Clifton,... 2015Aberrations in epigenome that include alterations in DNA methylation, histone acetylation, and miRNA (microRNA) expression may govern the progression of colorectal... (Review)
Review
Aberrations in epigenome that include alterations in DNA methylation, histone acetylation, and miRNA (microRNA) expression may govern the progression of colorectal cancer (CRC). These epigenetic changes affect every phase of tumor development from initiation to metastasis. Since epigenetic alterations can be reversed by DNA demethylating and histone acetylating agents, current status of the implication of epigenetic therapy in CRC is discussed in this article. Interestingly, DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) have shown promising results in controlling cancer progression. The information provided here might be useful in developing personalized medicine approaches.
Topics: Acetylation; Colorectal Neoplasms; DNA Methylation; Epigenesis, Genetic; Histones; Humans
PubMed: 25421691
DOI: 10.1007/978-1-4939-1804-1_40 -
Biochimica Et Biophysica Acta. Gene... Sep 2023Circadian rhythm is a roughly 24-h wake and sleep cycle that almost all of the organisms on the earth follow when they execute their biological functions and... (Review)
Review
Circadian rhythm is a roughly 24-h wake and sleep cycle that almost all of the organisms on the earth follow when they execute their biological functions and physiological activities. The circadian clock is mainly regulated by the transcription-translation feedback loop (TTFL), consisting of the core clock proteins, including BMAL1, CLOCK, PERs, CRYs, and a series of accessory factors. The circadian clock and the downstream gene expression are not only controlled at the transcriptional and translational levels but also precisely regulated at the post-translational modification level. Recently, it has been discovered that CLOCK exhibits lysine acetyltransferase activities and could acetylate protein substrates. Core clock proteins are also acetylated, thereby altering their biological functions in the regulation of the expression of downstream genes. Studies have revealed that many protein acetylation events exhibit oscillation behavior. However, the biological function of acetylation on circadian rhythm has only begun to explore. This review will briefly introduce the acetylation and deacetylation of the core clock proteins and summarize the proteins whose acetylation is regulated by CLOCK and circadian rhythm. Then, we will also discuss the crosstalk between lysine acetylation and the circadian clock or other post-translational modifications. Finally, we will briefly describe the possible future perspectives in the field.
Topics: CLOCK Proteins; Lysine; Acetylation; Circadian Rhythm; Protein Processing, Post-Translational
PubMed: 37453648
DOI: 10.1016/j.bbagrm.2023.194958 -
Journal of Neurochemistry Aug 2022Lysine acetylation is a reversible post-translational modification (PTM) involved in multiple physiological functions. Recent studies have demonstrated the involvement...
Lysine acetylation is a reversible post-translational modification (PTM) involved in multiple physiological functions. Recent studies have demonstrated the involvement of protein acetylation in modulating the biology of Schwann cells (SCs) and regeneration of the peripheral nervous system (PNS). However, the mechanisms underlying these processes remain partially understood. Here, we characterized the acetylome of the mouse sciatic nerve (SN) and investigated the cellular distribution of acetylated proteins. We identified 483 acetylated proteins containing 1442 acetylation modification sites in the SN of adult C57BL/6 mice. Bioinformatics suggested that these acetylated SN proteins were mainly located in the myelin sheath, mitochondrial inner membrane, and cytoskeleton, and highlighted the significant differences between the mouse SN and brain acetylome. Manual annotation further indicated that most acetylated proteins (> 45%) were associated with mitochondria, energy metabolism, and cytoskeleton and cell adhesion. We verified three newly discovered acetylation-modified proteins, including neurofilament light polypeptide (NEFL), neurofilament medium/high polypeptide (NFM/H), and periaxin (PRX). Immunofluorescence illustrated that the acetylated proteins, including acetylated alpha-tubulin, were mainly co-localized with S100-positive SCs. Herein, we provided a comprehensive acetylome for the mouse SN and demonstrated that acetylated proteins in the SN were predominantly located in SCs. These results will extend our understanding and promote further study of the role and mechanism of protein acetylation in SC development and PNS regeneration.
Topics: Acetylation; Animals; Lysine; Mice; Mice, Inbred C57BL; Protein Processing, Post-Translational; Proteome; Sciatic Nerve
PubMed: 35585794
DOI: 10.1111/jnc.15648 -
Comprehensive Reviews in Food Science... Jan 2021Meat quality plays an important role in the purchase decision of consumers, affecting producers and retailers. The formation mechanisms determining meat quality are... (Review)
Review
Meat quality plays an important role in the purchase decision of consumers, affecting producers and retailers. The formation mechanisms determining meat quality are intricate, as several endogenous and exogenous factors contribute during antemortem and postmortem periods. Abundant research has been performed on meat quality; however, unexpected variation in meat quality remains an issue in the meat industry. Protein posttranslational modifications (PTMs) regulate structures and functions of proteins in living tissues, and recent reports confirmed their importance in meat quality. The objective of this review was to provide a summary of the research on the effects of PTMs on meat quality. The effects of four common PTMs, namely, protein phosphorylation, acetylation, S-nitrosylation, and ubiquitination, on meat quality were discussed, with emphasis on the effects of protein phosphorylation on meat tenderness, color, and water holding capacity. The mechanisms and factors that may affect the function of protein phosphorylation are also discussed. The current research confirms that meat quality traits are regulated by multiple PTMs. Cross talk between different PTMs and interactions of PTMs with postmortem biochemical processes need to be explored to improve our understanding on factors affecting meat quality.
Topics: Acetylation; Meat; Phosphorylation; Protein Processing, Post-Translational; Proteins
PubMed: 33443799
DOI: 10.1111/1541-4337.12668 -
Autophagy 2018PIK3C3/VPS34 (phosphatidylinositol 3-kinase catalytic subunit type 3) converts phosphatidylinositol (PtdIns) to phosphatidylinositol-3-phosphate (PtdIns3P), sustaining...
PIK3C3/VPS34 (phosphatidylinositol 3-kinase catalytic subunit type 3) converts phosphatidylinositol (PtdIns) to phosphatidylinositol-3-phosphate (PtdIns3P), sustaining macroautophagy/autophagy and endosomal transport. So far, facilitating the assembly of the PIK3C3/VPS34-BECN1-PIK3R4/VPS15/p150 core complex at distinct membranes is the only known way to activate PIK3C3/VPS34 in cells. We have recently revealed a novel mechanism that regulates PIK3C3/VPS34 activation; cellular PIK3C3/VPS34 is repressed under nutrient-rich conditions by EP300/p300-mediated acetylation. Following nutrient-deprivation that drops EP300 activity, PIK3C3/VPS34 is liberated by deacetylation. Intriguingly, while deacetylation of the N-terminal K29 residue accounts for core complex formation, deacetylation at the C-terminal K771 site determines the binding of PIK3C3/VPS34 to its substrate PtdIns. In vitro and in cell evidence shows that EP300-dependent acetylation and deacetylation is a switch for turning off/on PIK3C3/VPS34 in which deacetylation of K771 is required for its full activation. This PIK3C3/VPS34 activation mechanism is utilized not only by starvation-induced autophagy but also by autophagy without the involvement of AMPK, MTORC1 or ULK1. These findings suggest an alternative circuit in cells for PIK3C3/VPS34 activation, which is involved in membrane transformations in response to metabolic and nonmetabolic cues.
Topics: Acetylation; Autophagy; Autophagy-Related Protein-1 Homolog; Autophagy-Related Proteins; Class III Phosphatidylinositol 3-Kinases
PubMed: 28980854
DOI: 10.1080/15548627.2017.1385676 -
Nature Communications Sep 2022Covalent attachment of ubiquitin (Ub) to proteins is a highly versatile posttranslational modification. Moreover, Ub is not only a modifier but itself is modified by...
Covalent attachment of ubiquitin (Ub) to proteins is a highly versatile posttranslational modification. Moreover, Ub is not only a modifier but itself is modified by phosphorylation and lysine acetylation. However, the functional consequences of Ub acetylation are poorly understood. By generation and comprehensive characterization of all seven possible mono-acetylated Ub variants, we show that each acetylation site has a particular impact on Ub structure. This is reflected in selective usage of the acetylated variants by different E3 ligases and overlapping but distinct interactomes, linking different acetylated variants to different cellular pathways. Notably, not only electrostatic but also steric effects contribute to acetylation-induced changes in Ub structure and, thus, function. Finally, we provide evidence that p300 acts as a position-specific Ub acetyltransferase and HDAC6 as a general Ub deacetylase. Our findings provide intimate insights into the structural and functional consequences of Ub acetylation and highlight the general importance of Ub acetylation.
Topics: Acetylation; Acetyltransferases; Lysine; Protein Processing, Post-Translational; Static Electricity; Ubiquitin; Ubiquitin-Protein Ligases
PubMed: 36114200
DOI: 10.1038/s41467-022-33087-1 -
Current Genetics May 2016Nε-acetylation is emerging as an abundant post-translational modification of bacterial proteins. Two mechanisms have been identified: one is enzymatic, dependent on an... (Review)
Review
Nε-acetylation is emerging as an abundant post-translational modification of bacterial proteins. Two mechanisms have been identified: one is enzymatic, dependent on an acetyltransferase and acetyl-coenzyme A; the other is non-enzymatic and depends on the reactivity of acetyl phosphate. Some, but not most, of those acetylations are reversed by deacetylases. This review will briefly describe the current status of the field and raise questions that need answering.
Topics: Acetylation; Acetyltransferases; Bacterial Proteins; Humans; Organophosphates; Protein Processing, Post-Translational
PubMed: 26660885
DOI: 10.1007/s00294-015-0552-4 -
Protein and Peptide Letters 2020The semi-synthetic acetoxycoumarins are known to acetylate proteins using novel enzymatic Calreticulin Transacetylase (CRTAase) system in cells. However, the...
BACKGROUND
The semi-synthetic acetoxycoumarins are known to acetylate proteins using novel enzymatic Calreticulin Transacetylase (CRTAase) system in cells. However, the nonenzymatic protein acetylation by polyphenolic acetates is not known.
OBJECTIVE
To investigate the ability of 7-acetoxy-4-methyl coumarin (7-AMC) to acetylate proteins non-enzymatically in the test tube.
METHODS
We incubated 7-AMC with BSA and analyzed the protein acetylation using Western blot technique. Further, BSA induced biophysical changes in the spectroscopic properties of 7-AMC was analyzed using Fluorescence spectroscopy.
RESULTS
Using pan anti-acetyl lysine antibody, herein we demonstrate that 7-AMC acetylates Bovine Serum Albumin (BSA) in time and concentration dependent manner in the absence of any enzyme. 7-AMC is a relatively less fluorescent molecule compared to the parental compound, 7- hydroxy-4-methylcoumarin (7-HMC), however the fluorescence of 7-AMC increased by two fold on incubation with BSA, depending on the time of incubation and concentration of BSA. Analysis of the reaction mixture of 7-AMC and BSA after filtration revealed that the increased fluorescence is associated with the compound of lower molecular weight in the filtrate and not residual BSA, suggesting that the less fluorescent 7-AMC undergoes self-hydrolysis in the presence of protein to give highly fluorescent parental molecule 7-HMC and acetate ion in polar solvent (phosphate buffered saline, PBS). The protein augmented conversion of 7-AMC to 7-HMC was found to be linearly related to the protein concentration.
CONCLUSION
Thus protein acetylation induced by 7-AMC could also be non-enzymatic in nature and this molecule can be exploited for quantification of proteins.
Topics: Acetylation; Animals; Cattle; Coumarins; Serum Albumin, Bovine
PubMed: 32133945
DOI: 10.2174/0929866527666200305143016 -
FASEB Journal : Official Publication of... Nov 2019Impaired glycolysis has pathologic effects on the occurrence and progression of liver diseases, and it appears that glycolysis is increased to different degrees in... (Review)
Review
Impaired glycolysis has pathologic effects on the occurrence and progression of liver diseases, and it appears that glycolysis is increased to different degrees in different liver diseases. As an important post-translational modification, reversible lysine acetylation regulates almost all cellular processes, including glycolysis. Lysine acetylation can occur enzymatically with acetyltransferases or nonenzymatically with acetyl-coenzyme A. Accompanied by the progression of liver diseases, there seems to be a temporal and spatial variation between enzymatic and nonenzymatic acetylations in the regulation of glycolysis. Here, we summarize the most recent findings on the functions and targets of acetylation in controlling glycolysis in the different stages of liver diseases. In addition, we discuss the differences and causes between enzymatic and nonenzymatic acetylations in regulating glycolysis throughout the progression of liver diseases. Then, we review these new discoveries to provide the potential implications of these findings for therapeutic interventions in liver diseases.-Li, J., Wang, T., Xia, J., Yao, W., Huang, F. Enzymatic and nonenzymatic protein acetylations control glycolysis process in liver diseases.
Topics: Acetylation; Acetyltransferases; Escherichia coli Proteins; Glycolysis; Humans; Liver Diseases; Protein Processing, Post-Translational
PubMed: 31370704
DOI: 10.1096/fj.201901175R