Acetylation: Formation of an acetyl derivative. (Stedman, 25th ed)Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.Histone Acetyltransferases: Enzymes that catalyze acyl group transfer from ACETYL-CoA to HISTONES forming CoA and acetyl-histones.p300-CBP Transcription Factors: A family of histone acetyltransferases that is structurally-related to CREB-BINDING PROTEIN and to E1A-ASSOCIATED P300 PROTEIN. They function as transcriptional coactivators by bridging between DNA-binding TRANSCRIPTION FACTORS and the basal transcription machinery. They also modify transcription factors and CHROMATIN through ACETYLATION.Acetyltransferases: Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1.Lysine: An essential amino acid. It is often added to animal feed.Histone Deacetylases: Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. The enzyme family can be divided into at least three structurally-defined subclasses. Class I and class II deacetylases utilize a zinc-dependent mechanism. The sirtuin histone deacetylases belong to class III and are NAD-dependent enzymes.Histone Deacetylase Inhibitors: Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains.Hydroxamic Acids: A class of weak acids with the general formula R-CONHOH.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.CREB-Binding Protein: A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.E1A-Associated p300 Protein: A member of the p300-CBP transcription factors that was originally identified as a binding partner for ADENOVIRUS E1A PROTEINS.Nucleosomes: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Histone Deacetylase 1: A histone deacetylase subtype that is found along with HISTONE DEACETYLASE 2; RETINOBLASTOMA-BINDING PROTEIN 4; and RETINOBLASTOMA-BINDING PROTEIN 7 as core components of histone deacetylase complexes.Sirtuin 1: A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation.Histone Deacetylase 2: A histone deacetylase subtype that is found along with HISTONE DEACETYLASE 1; RETINOBLASTOMA-BINDING PROTEIN 4; and RETINOBLASTOMA-BINDING PROTEIN 7 as core components of histone deacetylase complexes.Epigenesis, Genetic: A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Butyrates: Derivatives of BUTYRIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxypropane structure.Chromatin Immunoprecipitation: A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.Acetyl Coenzyme A: Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent.Methylation: Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Chromatin Assembly and Disassembly: The mechanisms effecting establishment, maintenance, and modification of that specific physical conformation of CHROMATIN determining the transcriptional accessibility or inaccessibility of the DNA.Sirtuin 3: A sirtuin family member found primarily in MITOCHONDRIA. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Sirtuins: A homologous family of regulatory enzymes that are structurally related to the protein silent mating type information regulator 2 (Sir2) found in Saccharomyces cerevisiae. Sirtuins contain a central catalytic core region which binds NAD. Several of the sirtuins utilize NAD to deacetylate proteins such as HISTONES and are categorized as GROUP III HISTONE DEACETYLASES. Several other sirtuin members utilize NAD to transfer ADP-RIBOSE to proteins and are categorized as MONO ADP-RIBOSE TRANSFERASES, while a third group of sirtuins appears to have both deacetylase and ADP ribose transferase activities.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Arylamine N-Acetyltransferase: An enzyme that catalyzes the transfer of acetyl groups from ACETYL-COA to arylamines. It can also catalyze acetyl transfer between arylamines without COENZYME A and has a wide specificity for aromatic amines, including SEROTONIN. However, arylamine N-acetyltransferase should not be confused with the enzyme ARYLALKYLAMINE N-ACETYLTRANSFERASE which is also referred to as SEROTONIN ACETYLTRANSFERASE.Sirtuin 2: A sirtuin family member found primarily in the CYTOPLASM. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.Acetic Anhydrides: Compounds used extensively as acetylation, oxidation and dehydrating agents and in the modification of proteins and enzymes.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.N-Terminal Acetyltransferase A: An N-terminal acetyltransferase subtype that consists of the Naa10p catalytic subunit and the Naa15p auxiliary subunit. The structure of this enzyme is conserved between lower and higher eukaryotes. It has specificity for N-terminal SERINE; ALANINE; THREONINE; GLYCINE; VALINE; and CYSTINE residues and acts on nascent peptide chains after the removal of the initiator METHIONINE by METHIONYL AMINOPEPTIDASES.Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester.Sulfamethazine: A sulfanilamide anti-infective agent. It has a spectrum of antimicrobial action similar to other sulfonamides.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.N-Terminal Acetyltransferase E: An N-terminal acetyltransferase subtype that consists of the Naa50p catalytic subunit, and the Naa10p and Naa15p auxiliary subunits. It has specificity for the N-terminal METHIONINE of peptides where the next amino acid in the chain is hydrophobic.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Anacardic Acids: A group of 6-alkyl SALICYLIC ACIDS that are found in ANACARDIUM and known for causing CONTACT DERMATITIS.Cell Line, Tumor: A cell line derived from cultured tumor cells.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.N-Terminal Acetyltransferases: Enzymes that catalyze the transfer of an acetyl group, usually from ACETYL COENZYME A, to the N-terminus of a peptide chain.Acetylesterase: An enzyme that catalyzes the conversion of acetate esters and water to alcohols and acetate. EC 3.1.1.6.Acetate-CoA Ligase: An enzyme that catalyzes the formation of CoA derivatives from ATP, acetate, and CoA to form AMP, pyrophosphate, and acetyl CoA. It acts also on propionates and acrylates. EC 6.2.1.1.Acetates: Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Chromosomal Proteins, Non-Histone: Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Histone-Lysine N-Methyltransferase: An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine. EC 2.1.1.43.

UK-18892, a new aminoglycoside: an in vitro study. (1/6505)

UK-18892 is a new aminoglycoside antibiotic, a derivative of kanamycin A structurally related to amikacin. It was found to be active against a wide range of pathogenic bacteria, including many gentamicin-resistant strains. The spectrum and degree of activity of UK-18892 were similar to those of amikacin, and differences were relatively minor. UK-18892 was about twice as active as amikacin against gentamicin-susceptible strains of Pseudomonas aeruginosa. Both amikacin and UK-18892 were equally active against gentamicin-resistant strains of P. aeruginosa. There were no appreciable differences in the activity of UK-18892 and amikacin against Enterobacteriaceae and Staphylococcus aureus. Cross-resistance between these two antimicrobials was also apparent.  (+info)

Prodigious substrate specificity of AAC(6')-APH(2"), an aminoglycoside antibiotic resistance determinant in enterococci and staphylococci. (2/6505)

BACKGROUND: High-level gentamicin resistance in enterococci and staphylococci is conferred by AAC(6')-APH(2"), an enzyme with 6'-N-acetyltransferase and 2"-O-phosphotransferase activities. The presence of this enzyme in pathogenic gram-positive bacteria prevents the successful use of gentamicin C and most other aminoglycosides as therapeutic agents. RESULTS: In an effort to understand the mechanism of aminoglycoside modification, we expressed AAC(6')-APH(2") in Bacillus subtilis. The purified enzyme is monomeric with a molecular mass of 57 kDa and displays both the expected aminoglycoside N-acetyltransferase and O-phosphotransferase activities. Structure-function analysis with various aminoglycosides substrates reveals an enzyme with broad specificity in both enzymatic activities, accounting for AAC(6')-APH(2")'s dramatic negative impact on clinical aminoglycoside therapy. Both lividomycin A and paromomycin, aminoglycosides lacking a 6'-amino group, were acetylated by AAC(6')-APH(2"). The infrared spectrum of the product of paromomycin acetylation yielded a signal consistent with O-acetylation. Mass spectral and nuclear magnetic resonance analysis of the products of neomycin phosphorylation indicated that phosphoryl transfer occurred primarily at the 3'-OH of the 6-aminohexose ring A, and that some diphosphorylated material was also present with phosphates at the 3'-OH and the 3"'-OH of ring D, both unprecedented observations for this enzyme. Furthermore, the phosphorylation site of lividomycin A was determined to be the 5"-OH of the pentose ring C. CONCLUSIONS: The bifunctional AAC(6')-APH(2") has the capacity to inactivate virtually all clinically important aminoglycosides through N- and O-acetylation and phosphorylation of hydroxyl groups. The extremely broad substrate specificity of this enzyme will impact on future development of aminoglycosides and presents a significant challenge for antibiotic design.  (+info)

Probing interactions between HIV-1 reverse transcriptase and its DNA substrate with backbone-modified nucleotides. (3/6505)

BACKGROUND: To gain a molecular understanding of a biochemical process, the crystal structure of enzymes that catalyze the reactions involved is extremely helpful. Often the question arises whether conformations obtained in this way appropriately reflect the reactivity of enzymes, however. Rates that characterize transitions are therefore compulsory experiments for the elucidation of the reaction mechanism. Such experiments have been performed for the reverse transcriptase of the type 1 human immunodeficiency virus (HIV-1 RT). RESULTS: We have developed a methodology to monitor the interplay between HIV-1 RT and its DNA substrate. To probe the protein-DNA interactions, the sugar backbone of one nucleotide was modified by a substituent that influenced the efficiency of the chain elongation in a characteristic way. We found that strand elongation after incorporation of the modified nucleotide follows a discontinuous efficiency for the first four nucleotides. The reaction efficiencies could be correlated with the distance between the sugar substituent and the enzyme. The model was confirmed by kinetic experiments with HIV-1 RT mutants. CONCLUSIONS: Experiments with HIV-1 RT demonstrate that strand-elongation efficiency using a modified nucleotide correlates well with distances between the DNA substrate and the enzyme. The functional group at the modified nucleotides acts as an 'antenna' for steric interactions that changes the optimal transition state. Kinetic experiments in combination with backbone-modified nucleotides can therefore be used to gain structural information about reverse transcriptases and DNA polymerases.  (+info)

High-throughput screening of small molecules in miniaturized mammalian cell-based assays involving post-translational modifications. (4/6505)

BACKGROUND: Fully adapting a forward genetic approach to mammalian systems requires efficient methods to alter systematically gene products without prior knowledge of gene sequences, while allowing for the subsequent characterization of these alterations. Ideally, these methods would also allow function to be altered in a temporally controlled manner. RESULTS: We report the development of a miniaturized cell-based assay format that enables a genetic-like approach to understanding cellular pathways in mammalian systems using small molecules, rather than mutations, as the source of gene-product alterations. This whole-cell immunodetection assay can sensitively detect changes in specific cellular macromolecules in high-density arrays of mammalian cells. Furthermore, it is compatible with screening large numbers of small molecules in nanoliter to microliter culture volumes. We refer to this assay format as a 'cytoblot', and demonstrate the use of cytoblotting to monitor biosynthetic processes such as DNA synthesis, and post-translational processes such as acetylation and phosphorylation. Finally, we demonstrate the applicability of these assays to natural-product screening through the identification of marine sponge extracts exhibiting genotype-specific inhibition of 5-bromodeoxyuridine incorporation and suppression of the anti-proliferative effect of rapamycin. CONCLUSIONS: We show that cytoblots can be used for high-throughput screening of small molecules in cell-based assays. Together with small-molecule libraries, the cytoblot assay can be used to perform chemical genetic screens analogous to those used in classical genetics and thus should be applicable to understanding a wide variety of cellular processes, especially those involving post-transitional modifications.  (+info)

A novel H2A/H4 nucleosomal histone acetyltransferase in Tetrahymena thermophila. (5/6505)

Recently, we reported the identification of a 55-kDa polypeptide (p55) from Tetrahymena macronuclei as a catalytic subunit of a transcription-associated histone acetyltransferase (HAT A). Extensive homology between p55 and Gcn5p, a component of the SAGA and ADA transcriptional coactivator complexes in budding yeast, suggests an immediate link between the regulation of chromatin structure and transcriptional output. Here we report the characterization of a second transcription-associated HAT activity from Tetrahymena macronuclei. This novel activity is distinct from complexes containing p55 and putative ciliate SAGA and ADA components and shares several characteristics with NuA4 (for nucleosomal H2A/H4), a 1.8-MDa, Gcn5p-independent HAT complex recently described in yeast. A key feature of both the NuA4 and Tetrahymena activities is their acetylation site specificity for lysines 5, 8, 12, and 16 of H4 and lysines 5 and 9 of H2A in nucleosomal substrates, patterns that are distinct from those of known Gcn5p family members. Moreover, like NuA4, the Tetrahymena activity is capable of activating transcription from nucleosomal templates in vitro in an acetyl coenzyme A-dependent fashion. Unlike NuA4, however, sucrose gradient analyses of the ciliate enzyme, following sequential denaturation and renaturation, estimate the molecular size of the catalytically active subunit to be approximately 80 kDa, consistent with the notion that a single polypeptide or a stable subcomplex is sufficient for this H2A/H4 nucleosomal HAT activity. Together, these data document the importance of this novel HAT activity for transcriptional activation from chromatin templates and suggest that a second catalytic HAT subunit, in addition to p55/Gcn5p, is conserved between yeast and Tetrahymena.  (+info)

Virus infection leads to localized hyperacetylation of histones H3 and H4 at the IFN-beta promoter. (6/6505)

Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP. In this report, we show that virus infection of cells results in a dramatic hyperacetylation of histones H3 and H4 that is localized to the IFN-beta promoter. Furthermore, expressing a truncated version of IRF-3, which lacks a p300/CBP interaction domain, suppresses both histone hyperacetylation and activation of the IFN-beta gene. Thus, coactivator-mediated localized hyperacetylation of histones may play a crucial role in inducible gene expression.  (+info)

Gibberellic acid stabilises microtubules in maize suspension cells to cold and stimulates acetylation of alpha-tubulin. (7/6505)

Gibberellic acid is known to stabilise microtubules in plant organs against depolymerisation. We have now devised a simplified cell system for studying this. Pretreatment of a maize cell suspension with gibberellic acid for just 3 h stabilised protoplast microtubules against depolymerisation on ice. In other eukaryotes, acetylation of alpha-tubulin is known to correlate with microtubule stabilisation but this is not established in plants. By isolating the polymeric tubulin fraction from maize cytoskeletons and immunoblotting with the antibody 6-11B-1, we have demonstrated that gibberellic acid stimulates the acetylation of alpha-tubulin. This is the first demonstrated link between microtubule stabilisation and tubulin acetylation in higher plants.  (+info)

Expanded lysine acetylation specificity of Gcn5 in native complexes. (8/6505)

The coactivator/adaptor protein Gcn5 is a conserved histone acetyltransferase, which functions as the catalytic subunit in multiple yeast transcriptional regulatory complexes. The ability of Gcn5 to acetylate nucleosomal histones is significantly reduced relative to its activity on free histones, where it predominantly modifies histone H3 at lysine 14. However, the association of Gcn5 in multisubunit complexes potentiates its nucleosomal histone acetyltransferase activity. Here, we show that the association of Gcn5 with other proteins in two native yeast complexes, Ada and SAGA (Spt-Ada-Gcn5-acetyltransferase), directly confers upon Gcn5 the ability to acetylate an expanded set of lysines on H3. Furthermore Ada and SAGA have overlapping, yet distinct, patterns of acetylation, suggesting that the association of specific subunits determines site specificity.  (+info)

Global alterations in histone acetylation levels have been observed in both normal and cancer cells and can be prognostic of clinical outcome. However, unlike site-specific acetylation changes that can affect transcription of particular genes, the reason for genome-wide changes has been less clear. Because acetyl-coA molecules required for histone acetylation and acetate anions generated by histone deacetylation are required for many metabolic processes, McBrian and colleagues hypothesized that metabolic or physiologic cues might affect global histone acetylation levels. Systematic testing of the effects of culture medium components on histone acetylation revealed that decreased sodium bicarbonate concentrations resulting in lowered extracellular and intracellular pH led to a rapid, marked reduction in total levels of histone H3 and H4 acetylation at multiple lysine residues. These pH-dependent changes were specific to histone acetylation, as histone methylation was unaffected and required ...
Protein acetylation affects gene expression, as well as other processes in cells, and it might be dependent on the availability of the metals. However, whether iron chelating compounds (siderophores) can have an effect on the acetylation process in plant roots is largely unknown. In the present study, western blotting and confocal microscopy was used to examine the degree of acetylation of histone H3 and alpha tubulin in Pinus sylvestris root cells in the presence of structurally different siderophores. The effect of metabolites that were produced by pathogenic and mycorrhizal fungi was also assessed. No effect was observed on histone acetylation. By contrast, the metabolites of the pathogenic fungus were able to decrease the level of microtubule acetylation, whereas treatment with iron-free ferrioxamine (DFO) was able to increase it. This latter was not observed when ferrioxamine-iron complexes were used. The pathogen metabolites induced important modifications of cytoskeleton organization.
Pathogen infection triggers complex molecular perturbations within host cells that results in either resistance or susceptibility. Protein acetylation is an emerging biochemical modification that appears to play central roles during host-pathogen interactions. To date, research in this area has focused on two main themes linking protein acetylation to plant immune signaling. Firstly, it has been established that proper gene expression during defense responses requires modulation of histone acetylation within target gene promoter regions. Second, some pathogens can deliver effector molecules that encode acetyltransferases directly within the host cell to modify acetylation of specific host proteins. Collectively these findings suggest that the acetylation level for a range of host proteins may be modulated to alter the outcome of pathogen infection. This review will focus on summarizing our current understanding of the roles of protein acetylation in plant defense and highlight the utility of proteomics
AbstractLysine acetylation is a reversible post-translational modification (PTM) which has been linked to many biological and pathological implications. Hence, localization of lysine acetylation is essential for deciphering the mechanism of such implications. Whereas many acetylated lysines in human proteins have been localized through experimental approaches in wet lab, it still fails to reach completion. In the present study, we proposed a novel feature extraction approach, bi-relative adapted binomial score Bayes (BRABSB), combined with support vector machines (SVMs) to construct a human-specific lysine acetylation predictor, which yields, on average, a sensitivity of 83.91%, a specificity of 87.25% and an accuracy of 85.58%, in the case of 5-fold cross validation experiments. Results obtained through the validation on independent data sets show that the proposed approach here outperforms other existing lysine acetylation predictors. Furthermore, due to the fact that global analysis of human ...
Posttranslational modification of proteins by acetylation and phosphorylation regulates most cellular processes in living organisms. Surprisingly, the evolutionary conservation of phosphorylated serine and threonine residues is only marginally higher than that of unmodified serines and threonines. With high-resolution mass spectrometry, we identified 1981 lysine acetylation sites in the proteome of Drosophila melanogaster. We used data sets of experimentally identified acetylation and phosphorylation sites in Drosophila and humans to analyze the evolutionary conservation of these modification sites between flies and humans. Site-level conservation analysis revealed that acetylation sites are highly conserved, significantly more so than phosphorylation sites. Furthermore, comparison of lysine conservation in Drosophila and humans with that in nematodes and zebrafish revealed that acetylated lysines were significantly more conserved than were nonacetylated lysines. Bioinformatics analysis using ...
The process of histone acetylation at lysine residues by histone acetyltransferase (HAT) is an important epigenetic marker and can be measured with the use of histone lysine acetylation antibodies . Acetylation of histones...
TY - JOUR. T1 - Acetylation of retinal histones in diabetes increases inflammatory proteins. T2 - Effects of minocycline and manipulation of histone acetyltransferase (HAT) and histone deacetylase (HDAC). AU - Kadiyala, Chandra Sekhar Rao. AU - Zheng, Ling. AU - Du, Yunpeng. AU - Yohannes, Elizabeth. AU - Kao, Hung Ying. AU - Miyagi, Masaru. AU - Kern, Timothy S.. PY - 2012/7/27. Y1 - 2012/7/27. N2 - Histone acetylation was significantly increased in retinas from diabetic rats, and this acetylation was inhibited in diabetics treated with minocycline, a drug known to inhibit early diabetic retinopathy in animals. Histone acetylation and expression of inflammatory proteins that have been implicated in the pathogenesis of diabetic retinopathy were increased likewise in cultured retinal Müller glia grown in a diabetes-like concentration of glucose. Both the acetylation and induction of the inflammatory proteins in elevated glucose levels were significantly inhibited by inhibitors of histone ...
Our collaboration with the group of Prof. Zheng on histone acetylation has led to a combined experimental/computational paper available from the Journal of Biological Chemistry.
The distribution of acetylated isoforms of histone H4 along Chinese hamster chromosomes has been studied by immunostaining with antibodies recognizing H4 acetylated at defined lysines in its N-terminal domain. The heterochromatic long arm of the X chromosome in both female (CHO) and male (DON) cell lines is underacetylated at three out of four lysines (5, 8, and 12). In contrast, the level of acetylation at lysine 16, which is the first to be acetylated in mammals, was similar in X chromosomes and autosomes. Labeling of the cells with bromodeoxyuridine (BrdU) to mark late-replicating chromosome domains, followed by double immunostaining with antibodies to BrdU and acetylated H4, showed a close, though not perfect, correlation between late replication and low levels of H4 acetylation. The results show that levels of histone acetylation are associated with the replication timing of defined domains on both the X chromosome and autosomes, but the exceptions we observe suggest that this link is not absolute
Newly synthesized histone H4 is deposited in a diacetylated isoform in a wide variety of organisms. In Tetrahymena a specific pair of residues, lysines 4 and 11, have been shown to undergo this modification in vivo. In this report, we demonstrate that the analogous residues, lysines 5 and 12, are acetylated in Drosophila and HeLa H4. These data strongly suggest that deposition-related acetylation sites in H4 have been highly, perhaps absolutely, conserved. In Tetrahymena and Drosophila newly synthesized histone H3 is also deposited in several modified forms. Using pulse-labeled H3 we have determined that, like H4, a specific, but distinct, subset of lysines is acetylated in these organisms. In Tetrahymena, lysines 9 and 14 are highly preferred sites of acetylation in new H3 while in Drosophila, lysines 14 and 23 are strongly preferred. No evidence has been obtained for acetylation of newly synthesized H3 in HeLa cells. Thus, although the pattern and sites of deposition-related acetylation appear ...
Many studies have shown that SIRT3 deficiency results in increased mitochondrial acetylation and reduced activity of numerous mitochondrial enzymes (Newman et al, 2012). SIRT3 protein levels are increased upon fasting and calorie restriction (Shi et al, 2005; Palacios et al, 2009; Hirschey et al, 2010; Tao et al, 2010; Newman et al, 2012), and increased SIRT3 activity has been suggested to regulate metabolism under these conditions. However, with the exception of a single study (Fan et al, 2014), a regulatory axis between enzyme‐catalyzed acetylation and SIRT3‐mediated deacetylation has not been demonstrated. A hallmark of protein regulation by posttranslational modifications is site‐specific, enzyme‐catalyzed modification that mostly occurs in a conditional manner. However, there is little evidence of enzyme‐catalyzed, site‐specific acetylation in mitochondria, and several studies suggest that most mitochondrial acetylation occurs nonenzymatically (Wagner & Payne, 2013; Pougovkina ...
Long-lasting memories require specific gene expression programmes that are, in part, orchestrated by epigenetic mechanisms. Of the epigenetic modifications identified in cognitive processes, histone acetylation has spurred considerable interest. Whereas increments in histone acetylation have consistently been shown to favour learning and memory, a lack thereof has been causally implicated in cognitive impairments in neurodevelopmental disorders, neurodegeneration and ageing. As histone acetylation and cognitive functions can be pharmacologically restored by histone deacetylase inhibitors, this epigenetic modification might constitute a molecular memory aid on the chromatin and, by extension, a new template for therapeutic interventions against cognitive frailty.. Read more → ...
Histone acetylation is a hallmark of chromatin that has an open structure that can be accessed by DNA and RNA polymerases as well as transcription factors, resulting in the activation of gene transcription (Filippakopoulos and Knapp, 2014). Correspondingly, histone methylation increases the basicity and hydrophobicity of histone tails and the affinity of certain proteins, such as transcription factors, toward DNA (Teperino et al., 2010), thus affecting the gene expression. In this database, we have collected 584 non-redundant protein data of 8 organisms including H. sapiens, M. musculus, R. norvegicus, D. melanogaster, C. elegans, A. thaliana, S. pombe and S. cerevisiae from the literature. The data are further classified into 15 families for histone acetylation writers, erasers and readers and 32 families for histone methylation writers, erasers and readers, respectively. WERAM 1.0 is a comprehensive Eukaryotic Writers, Erasers and Readers protein of Histone Acetylation and Methylation system ...
This study shows that Rb is a key regulator of differentiation and that acetylation is an important modification during this process. We have investigated the role of Rb acetylation in keratinocyte differentiation by mutating the major acetylation sites, lysines 873 and 874, to arginine and then determining the ability of the mutant to restore differentiation in Rb-knockdown keratinocytes. Mutation of the acetylation sites did not affect the ability of Rb to inhibit the proliferation, probably because of the fact that RbRR can interact with and inhibit E2F1 (Markham et al., 2006). This also suggests that inhibition of E2F family members is not sufficient to induce terminal differentiation, as has previously reported in the Saos-2 cell line (Sellers et al., 1998). However, unlike wild-type Rb, the acetylation mutant is unable to induce either early or late differentiation markers and, because Rb is acetylated relatively late during differentiation, this suggests that either the early events are ...
1. Acetylation Databases. (1) PhosphoSitePlus: (PSP) is a comprehensive, manually curated and interactive resource on post-translational modifications (PTM). PSP contains encompasses 130000 non-redundant modification sites, manily on phosphorylation, ubiquitinylation and acetylation (Hornbeck, et al., 2004). (2) g2pDB: A Database Mapping Protein Post-Translational Modifications to Genomic Coordinates. The original data comes mainly from published studies, many of which involve the investigation of post-translational modification acceptor site assignments, e.g., phosphorylation, ubiquitination, SUMOylation, acetylation, and N-linked glycosylation sites. (Keegan S, et al., 2016). (3) dbPTM 2.0: integrates experimentally verified PTMs from several databases, and to annotate the predicted PTMs on Swiss-Prot proteins , 2,071 acetylation sites were included while most of which were N-alpha-terminal ones (Lee TY, et al., 2006) . (4) HPRD release 9: HPRD currently contains information for 16,972 PTMs ...
TY - JOUR. T1 - Metabolic control of methylation and acetylation. AU - Su, Xiaoyang. AU - Wellen, Kathryn E.. AU - Rabinowitz, Joshua D.. PY - 2016/2/1. Y1 - 2016/2/1. N2 - Methylation and acetylation of DNA and histone proteins are the chemical basis for epigenetics. From bacteria to humans, methylation and acetylation are sensitive to cellular metabolic status. Modification rates depend on the availability of one-carbon and two-carbon substrates (S-adenosylmethionine, acetyl-CoA, and in bacteria also acetyl-phosphate). In addition, they are sensitive to demodification enzyme cofactors (α-ketoglutarate, NAD+) and structural analog metabolites that function as epigenetic enzyme inhibitors (e.g., S-adenosylhomocysteine, 2-hydroxyglutarate). Methylation and acetylation likely initially evolved to tailor protein activities in microbes to their metabolic milieu. While the extracellular environment of mammals is more tightly controlled, the combined impact of nutrient abundance and metabolic enzyme ...
|P>Eukaryotic transcription is a highly regulated process, and acetylation plays a major role in this regulation. Acetylation can occur on histones, DNA-binding TF (Transcription Factors), acetylases, nuclear import factors, non-nuclear proteins (Alpha-tubulin) and proteins that shuttle from the nucleus to [...]
Regulation of gene expression is mediated by several mechanisms including DNA methylation, ATP-dependent chromatin remodeling, and posttranslational modifications of histones. One of the major modifications of histones consists of the dynamic acetylation and deacetylation of ε-amino groups of lysine residues present in the tail of core histones.1 The enzymes responsible for this reversible acetylation/deacetylation process are histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively.2 While HATs act as transcriptional coactivators, HDACs are part of transcriptional corepressor complexes.
The two cotranslational processes, cleavage of N‐terminal methionine residues and N‐terminal acetylation, are by far the most common modifications, occurring on the vast majority of proteins. Proteins from prokaryotes, mitochondria and chloroplasts initiate with formylmethionine, whereas proteins from the cytosol of eukaryotes initiate with methionine. The formyl group is removed from prokaryotic proteins by a deformylase, resulting in methionine at the N‐termini. The methionine at the N‐termini is cleaved from nascent chains of most prokaryotic and eukaryotic proteins. N‐terminal acetylation occurs subsequently on certain of the proteins, either containing or lacking the methionine residue. This N‐terminal acetylation occurs on more than one‐half of eukaryotic proteins, but seldom on prokaryotic proteins (Driessen et al., 1985; Kendall et al., 1990).. Because the N‐terminal region of yeast iso‐1‐cytochrome c (iso‐1) is dispensable for biosynthesis, function and ...
TY - JOUR. T1 - The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. AU - Liu, Xin. AU - Wang, Ling. AU - Zhao, Kehao. AU - Thompson, Paul R.. AU - Hwang, Yousang. AU - Marmorstein, Ronen. AU - Cole, Philip A.. PY - 2008/2/14. Y1 - 2008/2/14. N2 - The transcriptional coactivator p300/CBP (CREBBP) is a histone acetyltransferase (HAT) that regulates gene expression by acetylating histones and other transcription factors. Dysregulation of p300/CBP HAT activity contributes to various diseases including cancer. Sequence alignments, enzymology experiments and inhibitor studies on p300/CBP have led to contradictory results about its catalytic mechanism and its structural relation to the Gcn5/PCAF and MYST HATs. Here we describe a high-resolution X-ray crystal structure of a semi-synthetic heterodimeric p300 HAT domain in complex with a bi-substrate inhibitor, Lys-CoA. This structure shows that p300/CBP is a distant cousin of other structurally characterized HATs, but ...
The 70kDa ribosomal protein S6 kinases (S6K1 and S6K2) play important roles in the regulation of protein synthesis, cell growth and survival. S6Ks are activated in response to mitogen stimulation and nutrient sufficiency by the phosphorylation of conserved serine and threonine residues. Here we show for the first time, that in addition to phosphorylation, S6Ks are also targeted by lysine acetylation. Following mitogen stimulation, S6Ks interact with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6Ks can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300. Furthermore, it appears that the acetylation sites targeted by p300 lie within the divergent C-terminal regulatory domains of both S6K1 and S6K2. Acetylation of S6K1 and 2 is increased upon the inhibition of class I/II histone deacetylases (HDACs) by trichostatin-A, while the enhancement of S6K1 acetylation by nicotinamide suggests the additional involvement of sirtuin ...
Caltag Medsystems provide a range of kits to study histone acetylation and histone deacetylation which is involved the addition or removal of an acetyl group on lysine residues in the N-terminal tail and on the surface of the nucelosome core of histone proteins. Acetylated and deacetylated histones are considered epigenetic tags within chromatin by relaxing (euchromatin) or tightening (heterochromatin) chromatin structure, subsequently increasing or decreasing gene transcription levels. Kits are available for Histone Acetylation Quantification, Histone Acetyltransferase (HAT) Assays, and Histone Deacetylase (HDAC) Assays.
Nucleosome structure incorporated histone acetylation site prediction in arabidopsis thaliana. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The epithelial to mesenchymal transition (EMT) enables epithelial cells with a migratory mesenchymal phenotype. It is activated in cancer cells and is involved in invasion, metastasis and stem-like properties. ZEB1, an E-box binding transcription factor, is a major suppressor of epithelial genes in lung cancer. In the present study, we show that in H358 non-small cell lung cancer cells, ZEB1 downregulates EpCAM (coding for an epithelial cell adhesion molecule), ESRP1 (epithelial splicing regulatory protein), ST14 (a membrane associated serine protease involved in HGF processing) and RAB25 (a small G-protein) by direct binding to these genes. Following ZEB1 induction, acetylation of histone H4 and histone H3 on lysine 9 (H3K9) and 27 (H3K27) was decreased on ZEB1 binding sites on these genes as demonstrated by chromatin immunoprecipitation. Of note, decreased H3K27 acetylation could be also detected by western blot and immunocytochemistry in ZEB1 induced cells. In lung cancers, H3K27 acetylation level
Jun dimerization protein-2 (JDP2) is a component of the AP-1 transcription factor that represses transactivation mediated by the Jun family of proteins. Here, we examine the functional mechanisms of JDP2 and show that it can inhibit p300-mediated acetylation of core histones in vitro and in vivo. Inhibition of histone acetylation requires the N-terminal 35 residues and the DNA-binding region of JDP2. In addition, we demonstrate that JDP2 has histone-chaperone activity in vitro. These results suggest that the sequence-specific DNA-binding protein JDP2 may control transcription via direct regulation of the modification of histones and the assembly of chromatin.
© 2014 The Authors. Gene transcription responds to stress and metabolic signals to optimize growth and survival. Histone H3 (H3) lysine 4 trimethylation (K4me3) facilitates state changes, but how levels are coordinated with the environment is unclear. Here, we show that isomerization of H3 at the alanine 15-proline 16 (A15-P16) peptide bond is influenced by lysine 14 (K14) and controls gene-specific K4me3 by balancing the actions of Jhd2, the K4me3 demethylase, and Spp1, a subunit of the Set1 K4 methyltransferase complex. Acetylation at K14 favors the A15-P16. trans conformation and reduces K4me3. Environmental stress-induced genes are most sensitive to the changes atK14 influencing H3 tail conformation and K4me3. By contrast, ribosomal protein genes maintain K4me3, required for their repression during stress, independently of Spp1, K14, and P16. Thus, the plasticity in control of K4me3, via signaling to K14 and isomerization at P16, informs distinct gene regulatory mechanisms and processes involving
Protein acetylation plays a critical regulatory role in eukaryotes but until recently its significance and function in bacteria and the archaea were obscure. It is now clear, however, that prokaryotes have the capacity to acetylate both the α-amino groups of N-terminal residues and the ε-amino group …
Histone acetyltransferase (HATs) proteins are involved in histone acetylation, or the addition of an acetyl group to lysine residues in the N-terminal tail and on the surface of the nucelosome core of histone proteins. They...
On the other hand, if acetylation is reduced, 53BP1 outcompetes BRCA1 at a break and the non-homologous end-joining tool repairs the break. This mechanism can help explain resistance to a promising chemotherapy called PARP inhibition seen in patients and mouse models with BRCA1 mutations. Work from several other research teams surprisingly has shown that if neither BRCA nor 53BP1 are available, then the homologous recombination system goes into action even in the absence of BRCA1 and BRCA1 mutant cancer cells become resistant to PARP inhibitors. Because of this, Greenberg says, there are some possible applications for making PARP chemotherapy more sensitive: "If you could inhibit specific acetylation events, then a patients response to PARP inhibitors might be enhanced by hyperactivating 53BP1 binding to breaks in the context of BRCA1 deficient cancers. Whats more, measuring the levels of acetylation at H4 might predict how responsive an individual is to PARP inhibitors." "The story didnt ...
Sir3 N-terminal acetylation stabilizes the interaction of Sir3 BAH with the NCP(a) Superposition of the structures of the N-terminally acetylated (pink) and una
Reversible acetylation of histone and non-histone proteins is one of the most abundant post-translational modifications in eukaryotic cells. Protein acetylation and deacetylation are achieved by the antagonistic actions of two families of enzymes, histone acetyltransferases (HATs) and histone deacet …
Statement of Research Interests. My research interests focus on the regulation of gene transcription in eukaryotic organisms, and the consequences of this regulation for downstream developmental events. In particular, I am interested in how factors such as covalent modifications of histones, chromatin structure/architecture, and gene organization may act and interact to influence gene expression.. Impact of histone acetylation on plant development. Background on HATs and Histone Acetylation. One area of current research investigates the biological role of the histone acetyltransferase (HAT) enzyme GCN5 in developmental pathways in the model plant Arabidopsis thaliana. GCN5 can covalently modify histones (chromatin proteins) by catalyzing the addition of acetyl group to specific lysine residues. This modification is hypothesized to affect histone-DNA contacts or provide binding sites for other factors involved in regulating transcription (the histone code hypothesis), but the exact biochemical ...
We have also investigated the potential roles of several signaling pathways, which could mediate apoptosis in the NPC cells upon treatment by bortezomib/SAHA. Bortezomib was found to potentiate SAHAs acetylation of histones H3 and H4 in the NPC cells. Furthermore, the histone acetylation was ROS- and caspase-8-dependent as both NAC- and caspase-8-specific inhibitor, Z-IETD-FMK, could markedly reduce the acetylation of the histones. The results were similar to the induction of caspase-8-dependent histone acetylation by combination of HDAC and proteasome inhibitors in leukemic cells (21). One of the major effects mediated by histone hyperacetylation is upregulation of tumor suppressor genes (9). However, we did not find any upregulation of retinoblastoma (Rb) or p53 in the bortezomib/SAHA-treated NPC cells (refer to Supplementary Fig. S2A). The p53 expression was repressed by the combination treatment in HA cells, whereas such repression was not found in C666-1 cells. Because enhanced apoptosis ...
Figure 3. Genetically encoded N-epsilon lysine acetylation allows the high resolution X-ray structures of acetylated proteins and their complexes to be solved. The high resolution structure of acetyl lysine from acetylated cyclophilin (left) showing the experimental density. Right, Acetylated cyclophilin in complex with cyclosporine. Water molecules (blue spheres) that are ordered at the protein small molecule interface in the unacetylated complex) rearrange in the acetylated complex.. The acetylation of a cyclophilin at Lys125 was identified in a proteomics screen. We subsequently demonstrated that a substantial proportion of CYPA is acetylated in HeLa cells and human T cell lines, suggesting that the acetylated form of the protein is biologically relevant. To test this, recombinant CYPA bearing homogenous acetylation at Lys125 was prepared by overexpression in E. coli using an acetyllysyl-tRNA synthetase-tRNACUA pair, allowing detailed biophysical and enzymatic characterization of acetylated ...
p53 is the most well-characterized tumor suppressor, and its tumor-suppressive functions are dysregulated in more than 50% of human tumor tissues (29). The MDM2 oncogene is frequently amplified in many tumor tissues to functionally inactivate p53 (5), suggesting that inhibition of MDM2 activity might provide a robust method for cancer prevention. Previous studies have demonstrated that p300 cooperates with MDM2 and triggers p53 polyubiquitination as a ubiquitin E4 ligase (11, 30). Here, we propose a novel regulatory mechanism for p300 via acetylation-dependent control of the oncogenic function of MDM2. Specifically, p300 directly acetylates MDM2, a process that channels that E3 ligase activity away from MDM2 autoubiquitination to concentrate on promoting p53 ubiquitination, in part because of acetylation-induced alteration of intramolecular interaction of MDM2. Thus, p300 may regulate p53 ubiquitination through multiple regulatory mechanisms.. Furthermore, we identified that acetylation of MDM2 ...
BioAssay record AID 632979 submitted by ChEMBL: Inhibition of HDAC4 in human HL60 cells assessed as increase in histone H4 acetylation at 1 ug/ml after 24 hrs by Western blot analysis.
Reversible acetylation of histone and nonhistone proteins plays pivotal role in cellular homeostasis. Dysfunction of histone acetyltransferases (HATs) leads to several diseases including cancer, neurodegenaration, asthma, diabetes, AIDS, and cardiac hypertrophy. We describe the synthesis and characterization of a set of p300-HAT-specific small-molecule inhibitors from a natural nonspecific HAT inhibitor, garcinol, which is highly toxic to cells. We show that the specific inhibitor selectively represses the p300-mediated acetylation of p53 in vivo. Furthermore, inhibition of p300-HAT down regulates several genes but significantly a few important genes are also upregulated. Remarkably, these inhibitors were found to be nontoxic to T cells, inhibit histone acetylation of HIV infected cells, and consequently inhibit the multiplication of HIV.. ...
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Histone deacetylation and rDNA silencing.Transcriptionally silenced regions of eukaryotic genomes are generally hypoacetylated. In S. cerevisiae, the HM loci and telomeres are hypoacetylated on histones H3 and H4, with an acetylation pattern similar to that in higher eukaryotes (10). The yeast RPD3 gene product is the proposed catalytic component of a large multiprotein histone deacetylase complex (HDB) which acts in targeted transcriptional repression (40, 64). Sin3p, another subunit of HDB, acts to target the complex to specific Pol II promoters through association with specific DNA binding proteins (41). Sap30p is also a member of this complex (84). Paradoxically,rpd3 and sin3 mutations increase silencing atHM loci (77), telomeres (23, 64), and the rDNA (this study). Similarly, Drosophila TPE is enhanced by null mutations of its RPD3 homolog (23). In another study, sap30 mutants strengthened all types of silencing in yeast, including the rDNA (37). These findings were completely consistent ...
Histones are proteins in close contact with the DNA in the nucleus of a cell. They function to maintain the organization of DNA, and recent studies have shown that histones regulate the expression of genes. Histones can be modified by biochemical processes such as addition or removal of acetyl groups, known as acetylation and deacetylation. Such modifications have been shown to control genetic mechanisms important for memory storage in brain cells.. Ottavio Arancio, M.D. and colleagues studied mice that had been genetically altered to exhibit Alzheimer-like pathology. They found that long-term potentiation-a cellular model of memory formation in the brain-was reduced by drugs that prevent deacetylation of histones. Furthermore, acetylation of histones in these animals was greatly reduced after a behavioral training session in comparison to normal mice. They have proposed to extend these studies to examine whether impairments in histone acetylation or deacetylation are involved in the memory ...
To determine whether PKM2 K62 and K305 are direct SIRT2 deacetylation targets, we generated a series of PKM2 K62 and K305 mutants, including Flag-PKM2, Flag-PKM2K62R, Flag-PKM2K305R, and Flag-PKM2K62R/K305R. In these mutants, the substitution of a lysine with an arginine mimics constitutive deacetylation (9). These vectors were subsequently transfected into HEK-293T cells, and an in vitro deacetylation assay was performed. These results showed that PKM2−K305R and PKM2−K62/K305R exhibited lower acetylation levels as compared with PKM2-K62R (Fig. 3D, lanes 3 and 4 vs. lane 2), suggesting that lysine 305, but not 62, is deacetylated by SIRT2. Thus, when K305 is mutated, only K62 can be acetylated, and as such, the greater acetylation in the presence of K62R means that K305 was the primary contributor to the acetylation, as has been shown by other (30), whereas the lower acetylation in the presence of K305R means that K62 was not acetylated.. A tissue culture deacetylation assay was performed ...
TRIP-Brs are a recently discovered set of proteins whose functions remain poorly characterized. Here we report the identification of TRIP-Br3 as a member of the TRIP-Br family along with evidence showing that TRIP-Brs interact with bromodomain-containing transcriptional cofactors PCAF, STAF65γ, and KAP1. PCAF, a histone acetyltransferase; STAF65γ, a protein associated with histone acetylation activity; and KAP1, a corepressor, influence the transcriptional activity of TRIP-Brs differentially. Finally, while all three TRIP-Brs are localized to the nucleus, TRIP-Br2 and TRIP-Br3 are also present in the cytoplasm through interaction with CRM1. Our results suggest that different TRIP-Brs function by interacting with a wide variety of bromodomain-containing transcriptional regulators in different subcellular locales ...
Histone acetylation plays a key role in the regulation of eukaryotic gene expression. Histone acetylation and deacetylation are catalyzed by multisubunit complexes. The protein encoded by this gene is a component of the histone deacetylase complex, which includes SIN3, SAP30, HDAC1, HDAC2, RbAp46, RbAp48, and other polypeptides. This protein directly interacts with SIN3 and enhances SIN3-mediated transcriptional repression when tethered to the promoter. A pseudogene has been identified on chromosome 2. [provided by RefSeq, Dec 2008] ...
Histone deacetylase (HDAC) inhibitors are undergoing clinical trials as anticancer agents, but some exhibit resistance mechanisms linked to anti-apoptotic Bcl-2 functions, such as BH3-only protein silencing. HDAC inhibitors that reactivate BH3-only family members might offer an improved therapeutic approach. We show here that a novel seleno-α-keto acid triggers global histone acetylation in human colon cancer cells and activates apoptosis in a p21-independent manner. Profiling of multiple survival factors identified a critical role for the BH3-only member Bcl-2-modifying factor (Bmf). On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein 3 (Sp3) transcription factor exchange and recruitment of p300. Treatment with a p300 inhibitor or transient overexpression of exogenous HDAC8 interfered with BMF induction, whereas RNAi-mediated silencing of STAT3 activated the target gene. This is the first report to
Specific genes that affect neuronal plasticity are crucial for long-term memory (Kandel et al., 2014). However, the molecules translated by these genes last only from several hours to several days, which may not maintain sufficient protein levels for long-term memory. In recent studies, epigenetics has been demonstrated to be the basis for the sustained regulation of gene transcription (Woldemichael et al., 2014). Specifically, histone acetylation has been thoroughly investigated in many mental diseases in recent years. Acetylation may occur in specific sites in histones and is regulated by two classes of enzymes, including histone acetyltransferase (HAT) and histone deacetylase (HDAC) (Szyf, 2014). The deacetylation of histones is induced by HDACs to ensure that DNA is tightly associated with histones and chromatin is "closed" for transcription (Narlikar et al., 2002; Penney and Tsai, 2014).. It has been reported that the nonspecific inhibitors of HDACs may significantly improve the performance ...
XRCC4-like factor (XLF) is the most recently discovered core member of the nonhomologous end joining (NHEJ) machinery. XLF enhances ligation of DNA ends by DNA ligase IV (LIG4) and functionally interacts with KU70. Previous results showed that some polymorphic changes in LIG4 impact on the efficiency of double strand breaks (DSBs) repair. A random Caucasian population sample was screened for XLF polymorphic mutations with similar functional impact. This analysis identified two novel noncoding single nucleotide polymorphisms (SNPs). To address the regulation of XLF and KU70, the acetylation status of both proteins were analysed. It has been found that XLF undergoes acetylation both in vitro and in vivo and the acetylation sites were mapped in vitro by mass spectrometry. Preliminary analysis has indicated that XLF deacetylation might be histone-deacetylase (HDAC3) dependent. For KU70, it has been found that lysine residues K317, K331 and K338 are critical for NHEJ. Cells overexpressing ...
Supplier: ProMab Technologies Type of Product: Monoclonal Antibody Description: HDAC3: histone deacetylase 3, also known as HD3, RPD3, RPD3-2. Entrez Protein NC_000005. Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters
View Notes - S10GenQuiz3Key from BIOL 283 at UMass (Amherst). A1. Youve isolated a mutant cell line that contains histones resistant to acetylation. What phenotype do you predict for this mutant? a.
There are comments on PubPeer for publication: Acetylation of RTN-1C regulates the induction of ER stress by the inhibition of HDAC activity in neuroectodermal tumors (2009)
Development of drugs that target epigenetic signaling mechanisms is a new and exciting strategy for the treatment of cancer. Epigenetic processes including chemical modifications to DNA and also to the histone proteins that package the DNA in chromatin play a central role in gene expression and regulation. One of the most frequently occurring modifications is the acetylation of lysine residues (Kac) and deregulation of this process has been associated with many common diseases, such as cancer, diabetes, obesity and Alzheimers disease. Historically, most therapeutic development has focused on the group of enzymes that "write" and "erase" acetylation marks on histones. But more recently, epigenetic "reader" proteins that sense the presence of these epigenetic marks are also being explored as novel therapeutic targets ...
Acetylation of H3 lysine 56 (H3K56Ac). H3K56Acx is required for genome stability.[88][89] H3K56 is acetylated by the p300/ ... Lysine acetylation[edit]. Addition of an acetyl group has a major chemical effect on lysine as it neutralises the positive ... Lysine acetylation appears to be less precise in meaning than methylation, in that histone acetyltransferases tend to act on ... H3K56 acetylation is also required to stabilise stalled replication forks, preventing dangerous replication fork collapses.[93] ...
This acetylation is catalyzed by acetyltransferases. This acetylation affects cell growth, mitosis, and apoptosis.[18] ... Acetylation *Acetyl-CoA is also the source of the acetyl group incorporated onto certain lysine residues of histone and ... The acetylation of CoA is determined by the carbon sources.[3][4] ... Ethanol also serves as a carbon source for acetylation of CoA utilizing the enzyme alcohol dehydrogenase.[8] ...
Main article: N-terminal acetylation. N-terminal acetylation is a form of protein modification that can occur in both ... It has been suggested that N-terminal acetylation can prevent a protein from following a secretory pathway.[4] ... "Towards a Functional Understanding of Protein N-Terminal Acetylation". PLoS Biology. 9: e1001074. doi:10.1371/journal.pbio. ...
some de-acetylation. Elimination half-life. 66-80 minutes. Excretion. Unchanged, in bile and urine. ...
Acetylation of alcohols and aminesEdit. Alcohols and amines are readily acetylated.[10] For example, the reaction of acetic ... Acetylation of aromatic ringsEdit. Aromatic rings are acetylated by acetic anhydride. Usually acid catalysts are used to ... Acetic anhydride is a versatile reagent for acetylations, the introduction of acetyl groups to organic substrates.[9] In these ... Similarly it is used in the production of aspirin (acetylsalicylic acid), which is prepared by the acetylation of salicylic ...
The EHD3 protein suffers three kinds of amino acid modifications: Acetylation. It consists of attaching an acetyl group at the ... "Acetylation". www.uniprot.org. Retrieved 2016-10-16. Chukkapalli, Sahiti; Amessou, Mohamed; Dekhil, Hafedh; Dilly, Ashok Kumar ...
Hydrolysis, reduction and acetylation yielded 136. Formation of a thiolactam followed by condensation with ethyl bromoacetate ...
Some acetylations involve terpenes like geraniol.[24] Those molecules are called meroterpenes (a chemical compound having a ...
This acetylation pattern has been seen during histone synthesis. Another example is acetylation of H4K16, which has been ... In general, histone acetylation increases gene expression.. In general, histone acetylation is linked to transcriptional ... However, acetylation is not always associated with enhanced transcriptional activity. For instance, acetylation of H4K12 has ... In flies, acetylation of H4K16 on the male X chromosome by MOF in the context of the MSL complex is correlated with ...
Selective acetylation of enzyme". Biochemistry. 7 (3): 913-919. doi:10.1021/bi00843a005. Schmidt, Donald E.; F.H. Westheimer ( ...
See also histone acetylation. The reverse is called deacetylation. formylation alkylation, the addition of an alkyl group, e.g ... Polevoda B, Sherman F; Sherman (2003). "N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of ... Yang XJ, Seto E; Seto (2008). "Lysine acetylation: codified crosstalk with other posttranslational modifications". Mol Cell. 31 ... acetylation, the addition of an acetyl group, either at the N-terminus of the protein or at lysine residues. ...
Col E, Gilquin B, Caron C, Khochbin S (2002). "Tat-controlled protein acetylation". J. Biol. Chem. 277 (40): 37955-60. doi: ... Randhawa GS, Bell DW, Testa JR, Feinberg AP (1998). "Identification and mapping of human histone acetylation modifier gene ... "UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation". EMBO J. 20 (12): ... "UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation". EMBO J. 20 (12): ...
"Acetylation of sulfanilamide by liver homogenates and extracts". J. Biol. Chem. 160 (1): 173-90. ...
Acetylation to N2-acetylphenelzine is a minor pathway. Phenelzine may also interact with cytochrome P450 enzymes, inactivating ...
Tabor H, Mehler AH, Stadtman ER (1953). "The enzymatic acetylation of amines". J. Biol. Chem. 204 (1): 127-138. PMID 13084583. ... Weissbach H, Redfield BG, Axelrod J (1961). "The enzymic acetylation of serotonin and other naturally occurring amines". ...
Friedman S, Fraenkel G (Dec 1955). "Reversible enzymatic acetylation of carnitine". Archives of Biochemistry and Biophysics. 59 ...
Tubulin acetylation is one of the signaling pathways for Na+ and K+-ATPase activity. Tubulin acetylation is also involved in ... Tubulin acetylation by ATAT1 has been shown to be elevated by the cell exposure to UV irradiation, as well as its exposure to ... The acetylation is used y the cell as a marker for these stable microtubules. ATAT1 specifically acetylates 'Lys-40' in alpha ... There are some cases in which the mutation of the gene might cause a reduction in the acetylation of the microtubules. Like for ...
Acetylation occurs on the lysine residues found at the amino N-terminal of histone tails. Histone acetylation is most commonly ... Valproic acid treatment increased mutant Htt H3 and H4 acetylation levels comparable to wild-type Htt in Drosophila models.[18] ... These studies have elucidated a decrease in acetylation of lysines 18 and 23 on N-terminal tails of histone 3 (H3K18 and H3K23 ... alpha-synuclein, the protein encoded by SNCA, can associate with histones and prevent their acetylation in concert with the ...
Acetylation is the most highly studied of these modifications. For example, acetylation of the K14 and K9 lysines of the tail ... acetylation at one position is likely to function differently from acetylation at another position. Also, multiple ... The acetylation event converts the positively charged amine group on the side chain into a neutral amide linkage. This removes ... For example, lysine acetylation may create a binding site for chromatin-modifying enzymes (or transcription machinery as well ...
Golebiowski F, Kasprzak KS (2007). "Inhibition of core histones acetylation by carcinogenic nickel(II)". Mol. Cell. Biochem. ... 2006). "Substrate and functional diversity of lysine acetylation revealed by a proteomics survey". Mol. Cell. 23 (4): 607-18. ...
Histone acetylation is also an important process in transcription. Histone acetyltransferase enzymes (HATs) such as CREB- ... During repair of DNA damages some individual repair events can alter the methylation of DNA and/or the acetylations or ... These are (1) histone acetylations and histone methylations, (2) DNA methylation at CpG sites, and (3) epigenetic ... Chronic nicotine intake in mice alters brain cell epigenetic control of gene expression through acetylation of histones. This ...
"Histone acetylation controls the inactive X chromosome replication dynamics". Nature Communications. 2. doi:10.1038/ncomms1218 ...
acetylation, Ubiquitination, SUMOylation, methylation, hydroxylation Methionine Met N-acetylation (N-terminus), oxidation to ... acetylation, the addition of an acetyl group, either at the N-terminus [10] of the protein or at lysine residues.[11] See also ... Phosphorylation, O-linked glycosylation, N-acetylation (N-terminus) Threonine Thr Phosphorylation, O-linked glycosylation, N- ... This acetylation is an activating mark for pronociceptin. The nociceptin/nociceptin opioid receptor system is involved in the ...
acetylation. Acetylation of the lysine amino groups is chemically analogous to the acetylation of the N-terminus. Functionally ... acetylation −. C. (. =. O. ). −. C. H. 3. {\displaystyle \mathrm {-C(=O)-CH_{3}} }. ... Similar to acetylation. Instead of a simple methyl group, the myristoyl group has a tail of 14 hydrophobic carbons, which make ... however, the acetylation of lysine residues is used to regulate the binding of proteins to nucleic acids. The cancellation of ...
Turner BM, O'Neill LP, Allan IM (1989). "Histone H4 acetylation in human cells. Frequency of acetylation at different sites ... 2001). "Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core ... Lusic M, Marcello A, Cereseto A, Giacca M (2004). "Regulation of HIV-1 gene expression by histone acetylation and factor ...
Acetylation is one such reaction. Some modifications include those for histones, p53, and tubulins. ... Acetylation is a vital chemical reaction that is important for co-translational and post-translational modification of proteins ... Some of the important Acetylation reactions include:-. N-alpha-terminal acetylation. This is the acetylation reaction of the N- ... Lysine acetylation and deacetylation. The histone acetylation and deacetylation occurs on the lysine residues in the N-terminal ...
Protein acetylation plays a critical regulatory role in eukaryotes but until recently its significance and function in bacteria ... Protein acetylation in prokaryotes Proteomics. 2011 Aug;11(15):3012-22. doi: 10.1002/pmic.201000812. Epub 2011 Jun 14. ... Like phosphorylation, acetylation appears to be an ancient reversible modification that can be present at multiple sites in ... Protein acetylation plays a critical regulatory role in eukaryotes but until recently its significance and function in bacteria ...
The lysine acetylation of STAT3 is also elevated in cancer cells. Since the acetylation of STAT3 is important for its oncogenic ... The acetylation of p53 is indispensable for its activation. It has been reported that the acetylation level of p53 will ... "Protein Acetylation: Much More than Histone Acetylation". Cayman Chemical. Archived from the original on 2014-02-28. Zhao S, Xu ... There are three major acetylation sites on p53: K164, K120 and C terminus. If only one of the acetylation sites is defected, ...
Acetylation control of cancer cell metabolism.. Lin R, Zhou X, Huang W, Zhao D, Lv L, Xiong Y, Guan KL, Lei QY1. ... Lysine acetylation plays an essential role in metabolism. Five individual studies have identified that a large number of ... the dysfunction of acetylation regulation in tumorigenesis and their potential role in cancer metabolism therapy. ... This review focuses on recent advances in the acetylation regulation of metabolic enzymes involved in the Warburg effect, ...
3. Nε-Acetylation. Acetylation occurring on the epsilon-amino group of lysine residues (. -acetylation) was discovered on ... Constitutively mimicking de-acetylation at K42 induced a nearly 60% increase in LCAD activity. Furthermore, acetylation at only ... acetylation focused almost exclusively on histone substrates [21-23]. It was not until 1996 that Taunton et al. purified the ... Mitochondrial acetylation biology is an infant field of study that, in the future, will have the potential to bridge our ...
Acetylation. Acetylation. In March 1996, a laboratory from the University of Rochester announced the discovery of an enzyme ... Now probably acetylation is one of the hottest topics in gene regulation.. Alliss lab succeeded in purifying a nuclear HAT ... Histone proteins have been known for years to be marked by other modifications besides acetylation, such as methylation, ... a homolog to yeast Gcn5p linking histone acetylation to gene activation, Cell, 84:843-851, 1996. (Cited in more than 250 ...
Increased histone acetylation has long been linked to gene activation, but little is known about how acetylation levels are ... The subunit-exchange model of histone acetylation.. Roth SY1, Allis CD. ...
David Dannheisig investigates the influence of lysine129 acetylation on the biological function of survivin including ... In his research, David Dannheisig investigates the influence of lysine129 acetylation on the biological function of survivin ... Zellbiologie Cancer Cell Biology Protein Interaction Studies Survivin Acetylation ...
For N-terminal acetylation in Drosophila, the (X)PX-rule (proline at first or second position inhibits acetylation) was used to ... It remains to be clarified whether differential histone acetylation is essential for H. volcanii or whether the acetylation of ... In contrast to eukaryotes, acetylation in E. coli occurs posttranslationally. Acetylation of S12 has been shown to stablize the ... The reason why the degree of N-terminal acetylation was overlooked for so long is probably that the acetylation typically is ...
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Acetylation is the process of adding an acetyl radical to a protein while a hydrogen atoms leaves it so that an acetate is ... Acetylation is one of the most studied processes in epigenetics. If proteins can control how DNA is replicated and the amount ... For acetylation to occur, N-alpha-acetyltransferases have to be present. There are three common variations of these that are ... There is a way acetylation is triggered by cellular proteins and when the reaction begins, chemicals are added to the DNA- ...
The acetylation pattern is regulated by HAT and HADC enzymes and, in turn, sets the local chromatin structure. In this way, ... Acetylation is the process where an acetyl functional group is transferred from one molecule (in this case, Acetyl-Coenzyme A) ... Acetylation has the effect of changing the overall charge of the histone tail from positive to neutral. Nucleosome formation is ... Acetylation removes the positive charge on the histones, thereby decreasing the interaction of the N termini of histones with ...
Control of metabolism by acetylation appears to be evolutionarily conserved: Wang et al. found that the ability of the ... Acetylation regulated various enzymes by distinct mechanisms, directly activating some, inhibiting one, and controlling the ... Now, two papers suggest that acetylation may represent an important regulatory mechanism controlling the function of metabolic ... Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux. Science 327, 1004-1007 (2010). [ ...
... Trends Genet. 2004 Apr;20(4):206-13. doi: 10.1016/j.tig.2004.02. ... Recent studies point to the importance of enzymes that control histone acetylation as stress-responsive regulators of gene ...
These defects can be reversed by restoring αK40 acetylation levels (18). On the other hand, elevated levels of αK40 acetylation ... Effects of α-tubulin acetylation on microtubule structure and stability. Lisa Eshun-Wilson, Rui Zhang, Didier Portran, Maxence ... Effects of α-tubulin acetylation on microtubule structure and stability. Lisa Eshun-Wilson, Rui Zhang, Didier Portran, Maxence ... 1986) The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules. J Cell Biol 103: ...
... by histone acetylation of the chromatin associated with the p21WAF1 gene and that HDAC inhibitor-induced histone acetylation ... by the degree of acetylation of the gene-associated histones and that this induced increase in acetylation is gene selective. ... 2B and 5A). No change in the levels of histone H4 acetylation was detected after culture with SAHA (Fig. 5B). Taken together, ... In this study, we have examined the effects of SAHA on the acetylation of histones in the chromatin of the p21WAF1 gene. We ...
Inhibition of histone acetylation requires the N-terminal 35 residues and the DNA-binding region of JDP2. In addition, we ... Here, we examine the functional mechanisms of JDP2 and show that it can inhibit p300-mediated acetylation of core histones in ... Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2. *Chunyuan Jin1,2. nAff8, ... Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat. Genet. 37, ...
In histone acetylation and deacetylation, the histones are acetylated and deacetylated on lysine residues ... In histone acetylation and deacetylation, the histones are acetylated and deacetylated on lysine residues in the N-terminal ... Acetylation brings in a negative charge, acting to neutralise the positive charge on the histones and decreases the interaction ... The source of the acetyl group in histone acetylation is Acetyl-Coenzyme A, and in histone deacetylation the acetyl group is ...
Increased levels of acetylation of mitochondrial proteins involved in energy metabolism subsequently contribute to the ... Heart Failure Linked To Increased Acetylation Of Mitochondrial Proteins. by Shirley Johanna on February 26, 2016 at 5:44 PM ... Using an unbiased screen to look for changes in protein acetylation, the researchers profiled heart tissue from 5 end-stage ... Further, in a mouse model, they detected elevated levels of mitochondrial protein acetylation at the earliest stages of heart ...
The rate of acetylation of hemoglobulin increased with pH up to approximately pH 8,5. Structural studies were done on ... There was no difference in the rate of acetylation of oxy- and deoxyhemoglobin. ASA acetylated column-purified hemoglobin A ... Quantitation of the extent of acetylation by densitometric scanning of gels agreed very well with estimates obtained from ...
Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux. By Qijun Wang, Yakun Zhang, Chen ... Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux. By Qijun Wang, Yakun Zhang, Chen ... Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux Message Subject. (Your Name) has ... Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown. We ...
... Thevenet L., Mejean C., Moniot B., Bonneaud ... We show that acetylation participates in the nuclear localisation of SRY by increasing SRY interaction with importin beta, ... In this study, we demonstrate that interaction of the human SRY with histone acetyltransferase p300 induces the acetylation of ... we suggest that acetylation and deacetylation of SRY may be important mechanisms for regulating SRY activity during mammalian ...
Protein acetylation is an emerging biochemical modification that appears to play central roles during host-pathogen ... To date, research in this area has focused on two main themes linking protein acetylation to plant immune signaling. Firstly, ... Collectively these findings suggest that the acetylation level for a range of host proteins may be modulated to alter the ... To date, research in this area has focused on two main themes linking protein acetylation to plant immune signaling. Firstly, ...
"Acetylation" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... This graph shows the total number of publications written about "Acetylation" by people in Harvard Catalyst Profiles by year, ... Class I HDAC inhibitors enhance YB-1 acetylation and oxidative stress to block sarcoma metastasis. EMBO Rep. 2019 12 05; 20(12 ... Below are the most recent publications written about "Acetylation" by people in Profiles. ...
We next examined whether the acetylation status of RelA regulates its assembly with IκBα. The acetylation of RelA induced by ... Acetylation levels of RelA determined by [3H]sodium acetate labeling (19) are shown in the upper panel. The total amount of T7- ... Acetylation of endogenous RelA was assessed by [3H]sodium acetate labeling (19) and is shown in the upper panel. The level of ... Duration of Nuclear NF-κB Action Regulated by Reversible Acetylation. By Lin-feng Chen, Wolfgang Fischle, Eric Verdin, Warner C ...
  • We found that acetylation of E2F1 is, instead, required to stabilize the protein in response to doxorubicin. (elsevier.com)
  • Acetic anhydride is a versatile reagent for acetylations , the introduction of acetyl groups to organic substrates. (wikipedia.org)
  • Our results unveil a differential role of P/CAF and p300 in acetylation-induced stabilization of E2F1, thus supporting a specific role for P/CAF HAT activity in E2F1-dependent apoptosis in response to DNA damage. (elsevier.com)
  • Acetylation (or in IUPAC nomenclature ethanoylation) describes a reaction that introduces an acetyl functional group into a chemical compound. (wikipedia.org)
  • Acetylation refers to the process of introducing an acetyl group (resulting in an acetoxy group) into a compound, namely the substitution of an acetyl group for an active hydrogen atom. (wikipedia.org)
  • Acetylation is the process where an acetyl functional group is transferred from one molecule (in this case, Acetyl-Coenzyme A) to another. (wikipedia.org)
  • Hi everybody, during a conversation with some chemists, I ve been told that formaldehyde reversing X-linking (high temperature and high salt concentration) may result in a loss of histone acetylation levels due to some similarities between the nature of bond that formaldehyde and the acetyl-group have. (protocol-online.org)
  • In Salmonella enterica, the lysine acetylation status of acetyl-CoA synthetase is regulated by CobB deacetylase, a Sir2 homolog in bacteria ( 21 , 26 ), as well as Pat acetyltransferase ( 27 ). (mcponline.org)
  • It has been shown that Pat is responsible for the acetylation and inactivation of Acs ( 2 ), while removal of the acetyl moiety of AcsAc by the CobB deacetylase reactivates the enzyme ( 12 ) ( Fig. 1 ). (asm.org)
  • Histone acetylation by histone acetyl transferases (HATs) and ATP-dependent chromatin remodelers (ADCRs) are implicated in chromatin remodeling, but the interplay between HATs and ADCRs in this process has not been fully elucidated. (nii.ac.jp)
  • Their results confirmed the formation of an acetyl-enzyme intermediate within the catalytic triad, suggesting a double-displacement mechanism for the O- acetylation reaction catalyzed by XOAT1. (plantcell.org)
  • The authors conclude that XOAT1 catalyzes xylan 2- O -acetylation through a double displacement bi-bi reaction involving the formation of an acetyl-enzyme intermediate. (plantcell.org)
  • Staphylococcus aureus (S. aureus), an opportunistic commensal pathogen, is highly resistant to lysozyme, because of the O-acetylation of peptidoglycan by O-acetyl transferase (oatA). (amrita.edu)
  • Cells of E. faecalis in the viable but nonculturable (VBNC) state had the highest levels of peptidoglycan O acetylation. (asm.org)
  • For each species and strain examined, the extent of peptidoglycan O acetylation is not stoichiometric but instead ranges typically between 20% and 70% relative to the muramic acid content. (asm.org)
  • Our data indicate that peptidoglycan O-acetylation plays an important role in S. aureus mediated septic arthritis. (amrita.edu)
  • Consistent with this computational analysis, the experimental data confirmed decrease in the growth, lysozyme induced lysis, and lysozyme resistance, due to peptidoglycan O-acetylation in S. aureus. (amrita.edu)
  • This is the first study to show significant changes in histone acetylation levels in the course of tumor progression from normal breast epithelium to in situ and invasive ductal carcinoma. (aacrjournals.org)
  • These results demonstrate that although TSA treatment induces a global increase in histone acetylation, specific locations of the genome, such as the MMTV promoter may be relatively unaffected. (uio.no)
  • The mcl1-101 mutation causes reduced CENP-A(Cnp1) in the central domain and an aberrant increase in histone acetylation in both domains.Mcl1 forms S-phase-specific nuclear foci, which colocalize with those of PCNA and Pol alpha.These results suggest that Mcl1 and Pol alpha are required for propagation of centromere chromatin structures during DNA replication. (nih.gov)
  • The mcl1-101 mutation causes reduced CENP-A(Cnp1) in the central domain and an aberrant increase in histone acetylation in both domains. (nih.gov)
  • Different NATs are responsible for the acetylation of nascent protein N-terminal, and the acetylation was found to be irreversible so far. (wikipedia.org)
  • This review will focus on summarizing our current understanding of the roles of protein acetylation in plant defense and highlight the utility of proteomics approaches to uncover the complete repertoire of acetylation changes triggered by pathogen infection. (frontiersin.org)
  • One PTM, lysine acetylation, has been traditionally studied in the context of nuclear histone modifications and is well known to influence changes in gene expression [ 1 ]. (hindawi.com)
  • Firstly, it has been established that proper gene expression during defense responses requires modulation of histone acetylation within target gene promoter regions. (frontiersin.org)
  • Based on these premises, we aimed to test the hypothesis that changes of histone acetylation also occur in patients with multiple sclerosis (MS), an inflammatory disease of the CNS, and that these changes are associated with widespread aberrant modulation of gene expression. (jneurosci.org)
  • Through a statistical analysis of conditional independence, we found that H4 acetylation may not have significant direct impact on global gene expression. (harvard.edu)
  • Increased histone acetylation is typically associated with an open chromatin state and higher gene expression levels, so rRNA transcript levels were measured in the 32E03-transgenic plants expressing both low and high levels of the effector. (plantcell.org)
  • This study demonstrates that sulfatide interaction with BRD1 mediates acetylation and is important for regulation of integrin αV gene expression. (aacrjournals.org)
  • Using high-resolution cryo-EM maps of acetylated and deacetylated microtubules, in conjunction with molecular-dynamics methods, we found that acetylation restricts the range of motion of the αK40 loop. (pnas.org)
  • View detailed Acetylation product specifications, including CAS number, molecular weight, molecular formula and chemical structure, by clicking on the product name. (scbt.com)
  • Molecular genetic basis of rapid and slow acetylation in mice. (aspetjournals.org)
  • The molecular genetic basis of N-acetylation polymorphism has been investigated in inbred mouse models of the human acetylation polymorphism. (aspetjournals.org)
  • now present structural and mechanistic details of XOAT1 that advance our understanding of the molecular mechanism of polysaccharide acetylation in plant cell walls. (plantcell.org)
  • We show that the Arabidopsis T-DNA insertion mutants of REDUCED WALL ACETYLATION 2 (rwa2), previously identified as having reduced O-acetylation of both pectins and hemicelluloses, exhibit pleiotrophic phenotype on the leaf surface. (osti.gov)
  • We studied the REDUCED WALL ACETYLATION (RWA) gene family of the hardwood model Populus to evaluate its potential for improving saccharification. (diva-portal.org)
  • Posttranslational modifications of alpha tubulin: detyrosination and acetylation differentiate populations of interphase microtubules in cultured cells. (rupress.org)
  • What is a slow acetylator and what is the role of acetylation in the pathophysiology of Stevens-Johnson syndrome (SJS)? (medscape.com)
  • There was no difference in the rate of acetylation of oxy- and deoxyhemoglobin. (greenmedinfo.com)
  • The rate of acetylation of hemoglobulin increased with pH up to approximately pH 8,5. (greenmedinfo.com)
  • The phenol group of glycyl tyrosine is acetylated by ketene under the conditions used in the acetylation of pepsin and the effect of pH on the rate of acetylation is similar in the two cases. (rupress.org)
  • Herein, we describe a novel and an efficient route for methylation and acetylation of aza-heteroarenes using PEG-400 under O 2 and TsOH·H 2 O for the first time by tuning the reaction conditions using a different set of starting materials. (rsc.org)
  • We identified multiple phosphorylation and acetylation sites and found that both modifications stabilise binding of ε and δ subunits. (nature.com)
  • Both of these modifications have been implicated as critical for NF-κB transactivation capacity, and thus, our results suggest that defects in key phosphorylation and acetylation events are important for the inhibition of NF-κB activity (and subsequent T cell function) in anergic CD8 + T cells. (jimmunol.org)
  • The implications of mitochondrial acetylation for the aging process will be discussed, as well as its potential implications for the unique and localized metabolic states that occur during the aging-associated conditions of heart failure and cancer growth. (hindawi.com)
  • The purpose of this study was to examine in detail the physiologic and acetylation changes of the heart that occur over time in a model of FRDA heart failure. (curefa.org)
  • This study was conducted to determine whether the slow acetylation phenotype is associated with an increased risk of hypersensitivity to TMP-SMX in patients with HIV infection. (ovid.com)
  • Of the 28 HIV-infected subjects, 20 (71%) expressed a slow acetylation phenotype and eight (29%) a fast phenotype. (ovid.com)
  • Of the 16 HIV-infected subjects with prior TMP-SMX hypersensitivity, 15 (94%) had a slow acetylation phenotype, whereas only five out of 12 (42%) non-hypersensitive subjects had a slow acetylation phenotype (P>0.01). (ovid.com)
  • A slow acetylation phenotype is a risk factor for hypersensitivity to TMP-SMX in HIV-infected subjects. (ovid.com)
  • In this study, we have investigated the mechanism by which INF2, a formin mutated in degenerative renal and neurological hereditary disorders, controls microtubule acetylation. (rupress.org)
  • The effect of INF2 silencing on microtubule acetylation was also observed in epithelial ECV304 cells, but not in Jurkat T cells. (rupress.org)
  • In this review, we bring together information indicating that such acetylation is widespread and that it is likely to regulate fundamental cellular processes. (nih.gov)