Acetylated and methylated lysine residues in histone H3 play important roles in regulating yeast gene expression and other cellular processes. Previous studies have suggested that histone H3 acetylated and methylated lysine residues may functionally interact through ...

... recruitment of the checkpoint adaptor protein 53BP1; and acetylation of several lysine residues in the N-terminal ... to the repair machinery. Accessibility of Damaged Sites Acetylation of histone tail...

Smad proteins regulate gene expression in response to TGFbeta signaling. Here we present evidence that Smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of Smad7 on two lysine residues in its N terminus. Acetylation or mutation of these lysine ...

Like phosphorylation, acetylation of lysine residues within a protein is considered a biologically relevant modification that controls the activity of target proteins. During stress of cells, massive protein acetylation takes place. Here, we show that p38 mitogen-activated protein kinase (MAPK), which controls many ...

(E1p) that is involved in decarboxylation of pyruvate followed by reductive acetylation of lipoic acid covalently bound to a lysine residue of ...

... responsible for chromatin remodeling that is required for gene expression (1-3). HATs acetylate histones at the lysine residues ...

... responsible for chromatin remodeling that is required for gene expression (1-3). HATs acetylate histones at the lysine residues ...

... The combination of ATRA with HCQ increased acetylation of N-terminal lysine residues on histones H3/H4 as well as caused direct HAT activation. ...

Histone Deacetylase Activity Is Necessary for Oligodendrocyte Lineage Progression Mireya Marin 08854 Gene expression can be modulated by chromatin changes induced by histone acetylation and deacetylation. Acetylation of histone lysine residues by acetyltransferases is associated with transcriptionally

The aspirin esterase activity of human plasma is due to butyrylcholinesterase and albumin. Our goal was to identify the amino acid residues involved in the aspirin esterase activity of albumin. Fatty acid free human albumin and human plasma were treated with aspirin for 5 min to 24 h. Acetylated residues were identified by LC/MS/MS and ...

Acetylation of lysine residues is a post-translational modification with broad relevance to cellular signalling and disease biology. Enzymes that 'write' (histone acetyltransferases, HATs) and 'erase' (histone deacetylases, HDACs) acetylation sites are an area of extensive research in current drug development, but ...

Acetylation of lysine residues is a post-translational modification with broad relevance to cellular signalling and disease biology. Enzymes that �write� (histone acetyltransferases, HATs) and �erase� (histone deacetylases, HDACs) acetylation sites are an area of extensive ...

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 ?-amino groups of N-terminal residues and the ?-amino groups of lysine side ...

Acetylation of the four lysine residues and the amino group of the terminal serine residue of Escherichia coli acyl carrier protein has no effect on the ability of this protein to function in fatty acid synthesis. Subsequent trypsin hydrolysis resulting in complete inactivation cleaves a single arginyl peptide ...

Proteomic studies have identified a plethora of lysine acetylated proteins in eukaryotes and bacteria. Determining the individual lysine acetyltransferases responsible for each protein acetylation mark is crucial for elucidating the underlying regulatory mechanisms, but has been challenging due to limited ...

There is emerging recognition of a novel fuel and redox sensing regulatory program that controls cellular adaptation via nonhistone protein lysine residue acetyl posttranslation modifications. This program functions in tissues with high energy demand and oxidative capacity and is highly enriched in the heart. Deacetylation is regulated ...

There is emerging recognition of a novel fuel and redox sensing regulatory program that controls cellular adaptation via non-histone protein lysine-residue acetyl post-translation modifications. This program functions in tissues with high energy demand and oxidative capacity and is highly enriched in the heart. Deacetylation is regulated by ...

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 ...

We characterized the effect of histone acetylation on the structure of a nucleosome and the interactions between two nucleosomes. In this study, nucleosomes reconstituted with the Selex "Widom 601" sequence were acetylated with the Piccolo NuA4 complex, which acetylates mainly H4 N-terminal tail lysine ...

BackgroundIt has been shown that molecular interactions between site-specific chemical modifications such as acetylation and methylation on DNA-packing histones and conserved structural modules present in transcriptional proteins are closely associated with chromatin structural changes and gene activation. Unlike methyl-lysine that can interact with ...

Genomic imprinting is an epigenetic inheritance system characterized by parental allele-specific gene expression. Allele-specific DNA methylation and chromatin composition are two epigenetic modification systems that control imprinted gene expression. To get a general assessment of histone lysine acetylation at imprinted genes we measured allele-specific ...

Sensitivities of Bromodomain Factors 1 and 2 to Histone H4 Acetylation specific lysine residues within the tails (Grunstein, 1997). The acetylation level of a locus is established by the competition between histone Department of Oral Biology mond, 1998). However, the "histone code" hypothesisHarvard School of ...

Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression. We used two animal models of inflammation of the bowel and biopsy samples from patients with Crohn's disease (CD) to study the expression of acetylated histones (H) 3 and 4 in inflamed mucosa. ...

Using a variety of biochemical and cell-based approaches, we show that estrogen receptor a (ER?) is acetylated by the p300 acetylase in a ligand- and steroid receptor coactivator (SRC)-dependent manner. Using mutagenesis and mass spectrometry, we identified two conserved lysine residues in ER? (Lys266 and Lys268) that are the primary ...

BackgroundAcetylation of promoter nucleosomes is tightly correlated and mechanistically linked to gene activity. However, transcription is not necessary for promoter acetylation. It seems, therefore, that external and endogenous stimuli control histone acetylation and by this contribute to gene regulation. Photosynthetic genes in ...

Receptor-interacting protein 140 is a co-regulator for many transcription factors. Previous mass spectrometry studies showed that either phosphorylation or lysine acetylation of RIP140 directly enhanced its trans-repressive activity. In this study, we first identified p300 as a specific lysine acetyltransferase, and ...

The covalent attachment of ubiquitin to proteins regulates numerous processes in eukaryotic cells. Here we report the identification of 753 unique lysine ubiquitylation sites on 471 proteins using higher-energy collisional dissociation on the LTQ Orbitrap Velos. In total 5756 putative ubiquitin substrates were identified. Lysine ...

The posttranslational modification of histone and other chromatin proteins has a well recognized but poorly defined role in the physiology of gene expression. With implications for interfering with these epigenetic mechanisms, we now report the existence of a relatively abundant secondary modification of chromatin proteins, the N⁶-formylation of lysine ...

SUMMARYHuntington�s disease (HD) is an incurable neurodegenerative disease caused by neuronal accumulation of the mutant protein huntingtin. Improving clearance of the mutant protein is expected to prevent cellular dysfunction and neurodegeneration in HD. We report here that such clearance can be achieved by posttranslational modification of the mutant Huntingtin (Htt) by ...

Homocitrate synthase (HCS) catalyzes aldol-type condensation of acetyl coenzyme A (acetyl-CoA) and ?-ketoglutarate (?-KG) to synthesize homocitrate (HC), which is the first and committed step in the lysine biosynthetic pathway through ?-aminoadipate. As known in most enzymes catalyzing the first reactions in amino acid biosynthetic ...

In affinity selection, calcineurin selects from a population of randomly modified calmodulins those species with which it prefers to interact. The method shows that acetylation of lysines affects calmodulin so as to interfere with its ability to interact with calcineurin. Monoacetylation of any lysine of calmodulin reduces its affinity ...

Pax3 plays a role in regulating Hes1 and Neurog2 activity and thereby stem cell maintenance and neurogenesis. A mechanism for Pax3 regulation of these two opposing events, during caudal neural tube development, is examined in this study. Pax3 acetylation on C-terminal lysine residues K437 and K475 may be critical for proper regulation ...

Pax3 plays a role in regulating Hes1 and Neurog2 activity and thereby stem cell maintenance and neurogenesis. A mechanism for Pax3 regulation of these two opposing events, during caudal neural tube development, is examined in this study. Pax3 acetylation on C-terminal lysine residues K437 and K475 may be critical for proper regulation ...

The thyroid hormone receptor (TR)-alpha is a nuclear receptor that mediates both transrepression and ligand-dependent transactivation. Here we show that TRalpha is posttranslationally modified by acetylation in response to its own ligand (T(3)). Acetylation increases binding to DNA. Using mutagenesis, we identified three conserved ...

The nuclear factor (NF)-?B transcription factor has essential roles in inflammation and oncogenesis. Its ubiquitous RelA subunit is regulated by several post-translational modifications, including phosphorylation, ubiquitination and acetylation. Ubiquitination promotes the termination of RelA-dependent transcription, but its regulation is incompletely understood. Through mass ...

The microtubule associated protein tau promotes neuronal survival through binding and stabilization of MTs. Phosphorylation regulates tau�microtubule interactions and hyperphosphorylation contributes to the aberrant formation of insoluble tau aggregates in Alzheimer�s disease (AD) and related tauopathies¹. However, other pathogenic post-translational tau modifications ...

Post-translational modifications (PTMs) of histones play important roles in regulating the structure and function of chromatin in eukaryotes. Although histone PTMs were considered to mainly occur at the N-terminal tails of histones, recent studies have revealed that PTMs also exist in the histone-fold domains, which are commonly shared among the core histones H2A, H2B, H3, and H4. The ...

... Lysine acetylation or Nε-acetylation, identified initially on core histones in 1968 [6], is mediated by a group of enzymes called histone ...

The oncogenic potential of the HTLV-1 Tax protein involves activation of the NF-{kappa}B pathway, which depends on Tax phosphorylation, ubiquitination and sumoylation. We demonstrate that the nuclei of Tax-expressing cells, including HTLV-1 transformed T-lymphocytes, contain a pool of Tax molecules acetylated on lysine residue at amino ...

Pob3p is an essential component of the S. cerevisiae FACT complex (yFACT). Several lines of evidence indicate that the yFACT complex plays an important role in chromatin assembly including the observation that the pob3 Q308K allele is synthetically lethal with an allele of histone H4 that prevents the diacetylation of newly synthesized molecules. We have analyzed the genetic interactions between ...

BackgroundAn essential event during the replication cycle of HIV-1 is the integration of the reverse transcribed viral DNA into the host cellular genome. Our former report revealed that HIV-1 integrase (IN), the enzyme that catalyzes the integration reaction, is positively regulated by acetylation mediated by the histone acetyltransferase (HAT) p300.ResultsIn this study we ...

Human albumin is thought to hydrolyze esters because multiple equivalents of product are formed for each equivalent of albumin. Esterase activity with p-nitrophenyl acetate has been attributed to turnover at tyrosine 411. However, p-nitrophenyl acetate creates multiple, stable, acetylated adducts, a property contrary to turnover. Our goal was to identify ...

Malondialdehyde (MDA), a naturally occurring dialdehyde produced in the membrane lipid peroxidation, is known to react with lysine residues of proteins, but the MDA-lysine adducts generated in the proteins have not been characterized adequately. In the present study, we provide evidence that the enaminal-type ...

BackgroundThe involvement of histone acetylation in facilitating gene expression is well-established, particularly in the case of histones H3 and H4. It was previously shown in Saccharomyces cerevisiae that gene expression was significantly down-regulated and chromatin more condensed in stationary phase compared to exponential phase. We were therefore interested in ...

Sirtuins comprise a family of enzymes found in all organisms, where they play a role in diverse processes including transcriptional silencing, aging, regulation of transcription, and metabolism. The predominant reaction catalyzed by these enzymes is NAD⁺-dependent lysine deacetylation, although some sirtuins exhibit a weaker ADP-ribosyltransferase ...

Sirtuins comprise a family of enzymes found in all organisms, where they play a role in diverse processes including transcriptional silencing, aging, regulation of transcription, and metabolism. The predominant reaction catalyzed by these enzymes is NAD{sup +}-dependent lysine deacetylation, although some sirtuins exhibit a weaker ADP-ribosyltransferase activity. Although the ...

The distinct biochemical function of endoplasmic reticulum (ER) protein Calreticulin (CR) catalyzing the transfer of acyl group from acyloxycoumarin to a receptor protein was termed calreticulin transacylase (CRTAase). The present study, unlike the previous reports of others utilizing CR-deficient cells alone, dealt with the recombinant CR domains of Heamonchus contortus (rhCRTAase) in order to ...

Brd4 is a member of the bromodomains and extra terminal domain (BET) family of proteins that recognize acetylated chromatin structures through their bromodomains and act as transcriptional activators. Brd4 functions as an associated factor and positive regulator of P-TEFb, a Cdk9-cyclin T heterodimer that stimulates transcriptional elongation by RNA polymerase II. Here, the ...

Histone acetylation is a major mechanism to regulate gene transcription. This post-translational modification is modified in cancer cells. In various tumor types the levels of acetylation at several histone residues are associated to clinical aggressiveness. By using immunohistochemistry we show that acetylated ...

Rtt109 is a protein acetyltransferase (PAT) that is responsible for the acetylation of lysine-56 of histone 3 (H3K56) in yeast. H3K56 acetylation has been implicated in the weakening of the interaction between the histone core and the surrounding DNA in the nucleosomal particle. Rtt109, in cooperation with various histone chaperones, ...

Recent proteomics studies have revealed that protein acetylation is an abundant and evolutionarily conserved post-translational modification from prokaryotes to eukaryotes. Although an astonishing number of acetylated proteins have been identified in those studies, the acetyltransferases that target these proteins remain largely unknown. Here we ...

Acetylation of lysine residues is conserved in all three kingdoms; however, its role in prokaryotes is unknown. Here we demonstrate that acetylation enables the reference bacterium Escherichia coli to withstand environmental stress. Specifically, the bacterium reaches higher cell densities and becomes more ...

An important issue for chromatin remodeling complexes is how their bromodomains recognize particular acetylated lysine residues in histones. The Rsc4 subunit of the yeast remodeler RSC contains an essential tandem bromodomain (TBD) that binds acetylated K14 of histone H3 (H3K14ac). We report a series of crystal ...

An important issue for chromatin remodeling complexes is how their bromodomains recognize particular acetylated lysine residues in histones. The Rsc4 subunit of the yeast remodeler RSC contains an essential tandem bromodomain (TBD) that binds acetylated K14 of histone H3 (H3K14ac). We report a series of crystal ...

Transcription factor activity is often controlled through the dynamic use of post-translational modifications. Two such modifications are acetylation and sumoylation, which both occur on lysine residues, providing the opportunity for cross-talk at the molecular level. Here, we focussed on the ETS-domain transcription factor PEA3 and ...

Evidence suggesting that eukaryotes and archaea use reversible N^?-lysine (N^?-Lys) acetylation to modulate gene expression has been reported, but evidence for bacterial use of N^?-Lys acetylation for this purpose is lacking. Here, we report data in support of the notion ...

Methods that introduce posttranslational modifications in a general, mild, and non-sequence-specific manner using biologically produced peptides have great utility for investigation of the functions of these modifications. In this study, the substrate promiscuity of a lantibiotic synthetase was exploited for the preparation of phosphopeptides, glycopeptides, and peptides containing analogs of ...

We used two chemical modifiers, tetranitromethane (TNM) and acetic anhydride, which specifically target accessible tyrosine and lysine residues, respectively, to modify Syrian hamster recombinant PrP(90-231) (rPrP) and PrP27-30, aiming at finding locations of conformational change. Modified proteins...

Acetylation of the ?-amino group of lysine (Lys) is a reversible posttranslational modification recently discovered to be widespread, occurring on proteins outside the nucleus, in most subcellular locations in mammalian cells. Almost nothing is known about this modification in plants beyond the well-studied acetylation of histone ...

Acetylation of the ?-amino group of lysine (Lys) is a reversible posttranslational modification recently discovered to be widespread, occurring on proteins outside the nucleus, in most subcellular locations in mammalian cells. Almost nothing is known about this modification in plants beyond the well-studied acetylation of histone ...

The hallmark of mammalian spermiogenesis is the dramatic chromatin remodeling process wherein the nucleosomal histones are replaced by the transition proteins TP1, TP2, and TP4. Subsequently these transition proteins are replaced by the protamines P1 and P2. Hyperacetylation of histone H4 is linked to their replacement by transition proteins. Here we report that TP2 is ...

SIRT1, a histone/protein deacetylase, and AMP-activated protein kinase (AMPK) are key enzymes responsible for longevity and energy homeostasis. We examined whether a mechanistic connection exists between these molecules that involves the major AMPK kinase LKB1. Initial studies demonstrated that LKB1 is acetylated in cultured (HEK293T) cells, mouse white adipose tissue, and ...

C-terminal binding protein (CtBP) has been shown to bind to a highly conserved five-amino-acid motif (PXDLS) located very close to the C-terminus of adenovirus early region 1A proteins. It has also been demonstrated that amino acids C-terminal and N-terminal to this original proposed binding site contribute to the interaction. However, conflicting evidence has been presented to show that ...

Lysine acetylation/deacetylation is increasingly being recognized as common post-translational modification that appears to be broadly operational throughout the cell. The functional roles of these modifications, outside of the nucleus, have not been extensively studied. Moreover, as acetyl-CoA donates the acetyl ...

The pRb (retinoblastoma protein) tumour suppressor protein has a crucial role in regulating the G1- to S-phase transition, and its phosphorylation by cyclin-dependent kinases is an established and important mechanism in controlling pRb activity. In addition, the targeted acetylation of lysine (K) residues 873/874 in the ...

Studies on the aggregation of mutant proteins have provided new insights into the genetics of amyloid diseases and the role of the net charge of the protein on the rate, extent, and type of aggregate formation. In the present work, hen egg white lysozyme (HEWL) was employed as the model protein. Acetylation and (separately) citraconylation were employed to neutralize the ...

Histone acetyltransferase and histone deacetylase are enzymes responsible for histone acetylation and deacetylation, respectively, in which the histones are acetylated and deacetylated on lysine residues in the N-terminal tail and on the surface of the nucleosome core. These processes are considered the most ...

Acetylated histones are generally associated with active chromatin. The bromodomain has recently been identified as a protein module capable of binding to acetylated lysine residues, and hence is able to mediate the recruitment of factors to acetylated chromatin. Functional studies of ...

eIF5A (eukaryotic translation initiation factor 5A) is the only cellular protein containing hypusine [N?-(4-amino-2-hydroxybutyl)lysine]. eIF5A is activated by the post-translational synthesis of hypusine and the hypusine modification is essential for cell proliferation. In the present study, we report selective acetylation of the hypusine and/or ...

SYNOPSISThe eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein containing hypusine, [N^?-(4-amino-2-hydroxybutyl)lysine]. eIF5A is activated by the posttranslational synthesis of hypusine and the hypusine modification is essential for cell proliferation. In this study, we report selective acetylation of ...

The human immunodeficiency virus type 1 (HIV-1) potent transactivator Tat protein mediates pleiotropic effects on various cell functions. Posttranslational modification of Tat affects its activity during viral transcription. Tat binds to TAR and subsequently becomes acetylated on lysine residues by histone acetyltransferases. Novel ...

The human transcriptional positive coactivator 4 (PC4) activates several p53-dependent genes. It has been demonstrated that this is a consequence of direct interaction with p53. Previously, we have concluded that PC4 interacts mainly with the C-terminal negative regulatory domain of p53 through its DNA binding C-terminal half. NMR chemical shift perturbation studies with peptide fragments ...

Haptens causing type I allergy have been shown to predominantly form lysine adducts in the carrier protein, while many haptens giving rise to type IV allergy preferentially form adducts with cysteine residues. Hexahydrophthalic anhydride derivatives are strong sensitizers capable of inducing allergic rhinitis, asthma and urticaria (type I allergy) and ...

Dosage compensation ensures equal expression of X-linked genes in males and females. In Drosophila, equalization is achieved by hypertranscription of the male X chromosome. This process requires an RNA/protein containing dosage compensation complex (DCC). Here we use RNA interference of individual DCC components to define the order of complex assembly in Schneider cells. We show that interaction ...

Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is involved in base excision DNA repair (BER) and in regulation of gene expression, acting as a redox co-activator of several transcription factors. Recent findings highlight a novel role for APE1 in RNA metabolism, which is modulated by nucleophosmin (NPM1). The results reported in this article show that five ...

Covalent modifications of intracellular proteins, such as phosphorylation, are generally thought to occur as secondary or tertiary responses to neurotransmitters, following the intermediation of membrane receptors and second messengers such as cyclic AMP. By contrast, the gasotransmitter nitric oxide directly S-nitrosylates cysteine residues in diverse intracellular proteins. ...

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an ...

The role of lysines 2 and 81 as target sites for acetylation in full-length HMGB1 and truncated tail-less protein, respectively, has been studied by mutation analysis for the abilities of these proteins to bind and bend DNA. The DNA bending ability of truncated tail-less HMGB1 containing Lys-2 mutated to alanine does not differ from that of the wild-type ...

Changes in expression levels of genes encoding for proteins that control metabolic pathways are essential to maintain nutrient and energy homeostasis in individual cells as well as in organisms. An important regulated step in this process is accomplished through covalent chemical modifications of proteins that form complexes with the chromatin of gene promoters. The peroxisome proliferators gamma ...

... Accession Number : AD0290717. Title : DETERMINATION OF HAZE AND INSOLUBLE RESIDUE AFTER ACETYLATION OF WOODPULP. ...

The chemical modification of hemoglobin by aspirin (ASA) has been studied, both in intact human red cells and in purified hemoglobin solutions. After incubation of red cells with 20 mM [acetyl-1minus14C]ASA, incorporation of radioactivity into hemoglobin was observed in agreement with the results of Klotz and Tam (1973. Proc. Natl. Acad. Sci. U. S. A. 70: 1313-1315). In ...

Type III effector proteins from bacterial pathogens manipulate components of host immunity to suppress defence responses and promote pathogen development. In plants, host proteins targeted by some effectors called avirulence proteins are surveyed by plant disease resistance proteins referred to as �guards�. The Ralstonia solanacearum effector protein PopP2 triggers immunity in Arabidopsis ...

A wide variety of nuclear regulators and enzymes are subjected to acetylation of the lysine residue, which regulates different aspects of protein functions. The MYST family histone acetyltransferase, human ortholog of MOF (hMOF), plays critical roles in transcription activation by acetylating nucleosomal H4K16. In ...

Hypoxia-inducible factor 1 alpha (HIF1?) is an essential part of the HIF-1 transcriptional complex that regulates angiogenesis, cellular metabolism and cancer development. In VHL-null kidney cancer cell lines, we previously reported that HIF1? proteins can be acetylated and inhibited by histone deacetylase inhibitors (HDACi) or specific siRNA against HDAC4. To investigate the ...

Abstract We have investigated the effects of 2 weeks of insulin-like growth factor-1 (IGF-1) supplementation (5??g/kg per day) and 6 weeks of exercise training (60% of the maximal oxygen consumption [VO(2) max]) on neurogenesis, DNA damage/repair, and sirtuin content in the hippocampus of young (3 months old) and old (26 months old) rats. Exercise improved the spatial memory of the old group, but ...

Protein ubiquitination is a post-translational modification (PTM) that regulates various aspects of protein function by different mechanisms. Global profiling of PTMs usually relies on purification and sequencing of PTM-containing peptides from proteolytic digests. Characterization of ubiquitination has lagged behind that of smaller PTMs, such as phosphorylation and ...

The copper-containing quinoenzyme semicarbazide-sensitive amine oxidase (EC 1.4.3.21; SSAO) is a multifunctional protein. In some tissues, such as the endothelium, it also acts as vascular-adhesion protein 1 (VAP-1), which is involved in inflammatory responses and in the chemotaxis of leukocytes. Earlier work had suggested that lysine might function as a recognition molecule ...

There are two main pathways in eukaryotic cells for the repair of DNA double-strand breaks: homologous recombination and nonhomologous end joining. Because eukaryotic genomes are packaged in chromatin, these pathways are likely to require the modulation of chromatin structure. One way to achieve this is by the acetylation of lysine ...

There are two main pathways in eukaryotic cells for the repair of DNA double-strand breaks: homologous recombination and nonhomologous end joining. Because eukaryotic genomes are packaged in chromatin, these pathways are likely to require the modulation of chromatin structure. One way to achieve this is by the acetylation of lysine ...

BackgroundThe proto-oncogene, c-Abl encodes a ubiquitously expressed tyrosine kinase that critically governs the cell death response induced by genotoxic agents such as ionizing radiation and cisplatin. The catalytic function of Abl, which is essential for executing DNA damage response (DDR), is normally tightly regulated but upregulated several folds upon IR exposure due to ATM-mediated ...

ABSTRACT: BACKGROUND: The proto-oncogene, c-Abl encodes a ubiquitously expressed tyrosine kinase that critically governs the cell death response induced by genotoxic agents such as ionizing radiation and cisplatin. The catalytic function of Abl, which is essential for executing DNA damage response (DDR), is normally tightly regulated but upregulated several folds upon IR exposure due to ...

The tumor suppressor p53 induces apo pto sis by altering the transcription of pro-apo pto tic targets in the nucleus and by a direct, nontranscriptional role at the mitochondria. Although the post-translational modifications regulating nuclear apo pto tic functions of p53 have been thoroughly characterized, little is known of how transcription-independent functions are controlled. We and others ...

Recent studies reveal that posttranslational modifications on chromatin proteins, especially histones, organize genomic DNA and mediate various cellular responses to environmental influences. Quantitative mass spectrometric analysis is a powerful approach to reveal these dynamic events on chromatin in a systematic manner. Here, the effects of arsenic exposure on histone epigenetic state were ...

The peptidase and esterase activities of rabbit pulmonary angiotensin converting enzyme (ACE) are rapidly abolished on reaction with 1-fluoro-2,4-dinitrobenzene (Dnp-F). Inactivation follows first-order kinetics with respect to the reagent and is accompanied by stoichiometric incorporation of 3,5-({sup 3}H)Dnp, indicating that the effect is due to a specific modification of the enzyme. Thin-layer ...

Autoacetylation of the p300 histone acetyltransferase controls the transition between VP16-mediated chromatin acetylation and preinitiation complex (PIC) assembly. Currently, it is unknown if and how autoacetylated p300 is deacetylated. We found that the NAD(+)-dependent histone deacetylase SIRT2 deacetylates p300 in vitro and in cells. SIRT2 deacetylates ...

Most published work on post-translational histone modifications focuses on small covalent alterations such as acetylation, methylation and phosphorylation. By contrast, fewer data are available on the modification of histones by ADP-ribose. Discussion of the biological significance of histone ADP-ribosylation has often been restricted to functions of the modifying enzymes, ...

The transcriptional and chromatin profile of the promoter, first exon and first intron of the human TH gene were analyzed in human neuroblastoma BE(2)-C-16 and human renal carcinoma 293FT cell lines. The latter is a cell culture system that is not permissive for TH gene expression, whereas the former has a 50% cell fraction that tests positive for TH. The engineering of a 6.3 kb recombinant human ...

The activity of the p53 gene product is regulated by a plethora of posttranslational modifications. An open question is whether such posttranslational changes act redundantly or dependently upon one another. We show that a functional interference between specific acetylated and phosphorylated residues of p53 influences cell fate. ...

Blue light-induced transcription in Neurospora crassa is regulated by the White Collar-1 (WC-1) photoreceptor. We report that residue K14 of histone H3 associated with the light-inducible albino-3 (al-3) promoter becomes transiently acetylated after photoinduction. This acetylation depends on WC-1. The relevance of this chromatin ...

The cotranslational modification of N-terminal acetylation is ubiquitous among eukaryotes and has been reported to have a wide range of biological effects. The human N-terminal acetyltransferase (NAT) Naa50p (NAT5/SAN) acetylates the ?-amino group of proteins containing an N-terminal methionine residue and is essential for proper ...

Propionylation has been identified recently as a new type of protein post-translational modification. Bacterial propionyl-CoA synthetase and human histone H4 are propionylated at specific lysine residues that have been known previously to be acetylated. However, other proteins subject to this modification remain to be identified, and ...

Methylation of histone H3 lysine 4 (H3K4me) is an evolutionarily conserved modification whose role in the regulation of gene expression has been extensively studied. In contrast, the function of H3K4 acetylation (H3K4ac) has received little attention because of a lack of tools to separate its function from that of H3K4me. Here we show that, in addition to ...

Reversible posttranslational modification of internal lysines in many cellular or viral proteins is now emerging as part of critical signalling processes controlling a variety of cellular functions beyond chromatin and transcription. This paper aims at demonstrating the role of lysine acetylation in the cytoplasm driving and ...

Lysine acetylation (LysAc), a form of reversible protein post translational modification previously known only for histone proteins in plants, is shown to be wide spread in Arabidopsis. Sixty five lysine modification sites were identified on 58 proteins, which operate in a wide variety of pathways/...

A detailed {sup 1}H NMR analysis of ligand binding to the human plasminogen kringle 4 domain has been carried out at 300 MHz. The ligands that were investigated are N{sup {alpha}}-acetyl-L-lysine, L-lysine methyl ester, N{sup {alpha}}-acetyl-L-lysine methyl ester, L-lysine hydroxamic acid, ...

Metal-dependent histone deacetylases (HDACs) catalyze the hydrolysis of acetyl-l-lysine side chains in histone and nonhistone proteins to yield l-lysine and acetate. This chemistry plays a critical role in the regulation of numerous biological processes. Aberrant HDAC activity is implicated in various diseases, and HDACs are validated targets for drug ...

Rtt109, also known as KAT11, is a recently characterized fungal-specific histone acetyltransferase (HAT) that modifies histone H3 lysine 56 (H3K56) to promote genome stability. Rtt109 does not show sequence conservation with other known HATs and depends on association with either of two histone chaperones, Asf1 or Vps75, for HAT activity. Here we report the X-ray crystal ...

Rtt109, also known as KAT11, is a recently characterized fungal-specific histone acetyltransferase (HAT) that modifies histone H3 lysine 56 (H3K56) to promote genome stability. Rtt109 does not show sequence conservation with other known HATs and depends on association with either of two histone chaperones, Asf1 or Vps75, for HAT activity. Here we report the X-ray crystal ...

... differentiation. Oxygen is a substrate for the extremely important post- translational hydroxylation of proline and lysine residues in collagen. ...

Nat4, also designated NatD, was previously shown to acetylate the N termini of histones H2A and H4, which have SGGKG and SGRGK N termini (O. K. Song, X. Wang, J. H. Waterborg, and R. Sternglanz, J. Biol. Chem. 278:38109-38112, 2003). The analysis of chimeric proteins with various N-terminal segments of histone H4 fused to iso-1-cytochrome c revealed that efficient ...

Human exposure to trihalomethanes such as chloroform has been associated with both cancer and reproductive toxicity. While there is little evidence for chloroform mutagenicity or DNA adduct formation, in vivo studies in rats have demonstrated adduction to histones and other nuclear proteins. Histones play a key role in controlling DNA expression particularly through the ...

Acetic anhydride in anhydrous acetone-triethylamine reacts with decalcified bone collagen in two ways. It completely acetylates the e-amino groups of lysine and hydroxylysine and causes a progressive change in the protein matrix, such that increasing amounts of degraded peptides become soluble in alkaline phosphate solution. The peptides produced have ...

Histone acetyltransferases (HATs) catalyze the transfer of an acetyl group from an acetyl-coenzyme A donor molecule to specific lysine residues within proteins. The acetylation state of proteins, particularly histones, is known to modulate their intermolecular binding properties and control ...

Modification of proteins of the translational apparatus is common in many organisms. In the yeast Saccharomyces cerevisiae, we provide evidence for the methylation of Rpl1ab, a well conserved protein forming the ribosomal L1 protuberance of the large subunit that functions in the release of tRNA from the exit site. We show that the intact mass of Rpl1ab is 14 Da larger than its calculated mass ...

Signaling through the kinase Akt regulates many biological functions. Akt is activated during growth factor stimulation through a process that requires binding of Akt to phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), which promotes membrane localization and phosphorylation of Akt by the upstream kinase PDK1 (phosphoinositide-dependent protein kinase 1). We show that Akt and PDK1 are ...

This paper introduces a flexible assay for characterizing the activities of the histone deacetylase enzymes. The approach combines mass spectrometry with self-assembled monolayers that present acetylated peptides and enables a label-free and one-step assay of this biochemical activity. The assay was used to characterize the activity of HDAC8 toward peptides taken from the ...

In recent years, protein lysine acetylation has emerged as a prominent and conserved regulatory posttranslational modification that is abundant on numerous enzymes involved in the processes of intermediary metabolism. Well-characterized mitochondrial processes of carbon utilization are enriched in acetyl-lysine modifications. Although ...

The type I collagen alpha chains with or without non-helical ... of pyruvate followed by reductive acetylation of lipoic acid covalently bound to a lysine ...

Cloning and Characterization of an alpha-amylase Gene from the ... of pyruvate followed by reductive acetylation of lipoic acid covalently bound to a lysine ...

The horse heart cytochrome c contains nineteen lysine residues that constitute 18% of the amino acid residues in the protein. These lysine residues are widely spread throughout the structure of the protein. Acylation of cytochrome c with succinic anhydride produces different partially ...

Post-translational modifications of histones play important roles in regulating chromatin dynamics and epigenetic inheritance during mitosis. The epigenetic significance and stability of histone H3-lysine 9 (H3K9) modifications have been well studied in interphase cells, whereas not as much in mitotic cells. Here, we inspected mitosis-coupled alterations in the global ...

Activated phagocytes produce the highly reactive oxidant hypochlorous acid (HOCl) via the myeloperoxidase-catalysed reaction of hydrogen peroxide with chloride ions. HOCl reacts readily with a number of susceptible targets on apolipoprotein B-100 of low-density lipoprotein (LDL), resulting in uncontrolled uptake of HOCl-modified LDL by macrophages. We have investigated the effects of vitamin C ...

Furan is a rodent hepatotoxicant and carcinogen. Since this compound is an important industrial intermediate and has been detected in heat-processed foods and smoke, humans are likely exposed to this toxic compound. Characterization of urinary metabolites of furan will lead to the development of biomarkers to assess human health risks associated with furan exposure. Previous studies indicate that ...

Histone variant H3.3 is associated with transcriptionally active chromatin and accumulates at loci undergoing preparation for V(D)J recombination, a DNA rearrangement required for the assembly of antigen receptors and development of B and T lymphocytes. Here we demonstrate that the RAG1 V(D)J recombinase protein promotes ubiquitylation of H3.3 that has been heavily acetylated ...

Silent chromatin formation in Saccharomyces cerevisiae begins with the recruitment of silent information regulator (Sir) proteins to silencers at the silent mating-type loci and to telomere ends. Next, Sir2/3/4 proteins propagate across these loci as histones are deacetylated by the NAD(+)-dependent histone deacetylase Sir2p, ultimately resulting in the cessation of transcription and in the loss ...

Esa1 is the only essential histone acetyltransferase (HAT) in budding yeast. It is the catalytic subunit of at least two multiprotein complexes, NuA4 and Piccolo NuA4 (picNuA4), and its essential function is believed to be its catalytic HAT activity. To examine the role of Esa1 in DNA damage repair, we isolated viable esa1 mutants with a range of hypersensitivities to the toposide camptothecin. ...

The NAD-dependent histone deacetylase Sirt1 is a negative regulator of T cell activation. Here we report that Sirt1 inhibits T cell activation by suppressing the transcription of Bcl2-associated factor 1 (Bclaf1), a protein required for T cell activation. Sirt1-null T cells have increased acetylation of the histone 3 lysine 56 residue ...

N-terminal tails of H2A, H2B, H3 and H4 histone families are subjected to posttranslational modifications that take part in transcriptional regulation mechanisms, such as transcription factor binding and gene expression. Regulation mechanisms under control of histone modification are important but remain largely unclear, despite of emerging datasets for comprehensive analysis of histone ...

Recruitment of modifiers and remodelers to specific DNA sites within chromatin plays a critical role in controlling gene expression. The study of globin gene regulation provides a convergence point within which to address these issues in the context of tissue-specific and developmentally regulated expression. In this regard, erythroid Kr�ppel-like factor (EKLF) is critical. EKLF is a red ...

Histone acetylation plays a role in the regulation of gene transcription. Yet it is not known whether post-mortem brain tissue is suitable for the analysis of histone acetylation. To examine this question, nucleosomes were isolated from frontal cortex of nine subjects which were obtained at short times after death and immediately frozen at -80�C or ...

Histone modifications, such as acetylation and methylation, are important epigenetic marks that regulate diverse biological processes that use chromatin as the template, including transcription. Dysregulation of histone acetylation and methylation leads to the silencing of tumor suppressor genes and contributes to cancer progression. Inhibitors of enzymes ...

Proteolytic processing events are essential to physiological processes such as reproduction, development, and host responses, as well as regulating proteins in cancer; therefore, there is a significant need to develop robust approaches for characterizing such events. The current mass spectrometry (MS)-based proteomics techniques employs a �bottom-up� strategy, which does not allow for ...

Sirtuins are NAD(+)-dependent class III histone deacetylases, which catalyze the deacetylation of acetyl-lysine residues of histones and other protein substrates yielding the deacetylated protein, nicotinamide and 2'-O-acetyl-ADP-ribose. Two lysine amide derivatives containing dansyl (Dns) or ...

N?-acetyl-?-lysine is an archaeal compatible solute whose synthesis is mediated by the sequential reactions of the lysine-2,3-aminomutase AblA and the acetyltransferase AblB. ?-Lysine serves as the precursor and is converted by AblA to ?-lysine, and AblB then acetylates this intermediate to ...

ABSTRACT: The biochemical landscape of lysine acetylation has expanded from a small number of proteins in the nucleus to a multitude of proteins in the cytoplasm. Since the first report confirming acetylation of the tumor suppressor protein p53 by a lysine acetyltransferase (KAT), there has been a surge in the ...

The biochemical landscape of lysine acetylation has expanded from a small number of proteins in the nucleus to a multitude of proteins in the cytoplasm. Since the first report confirming acetylation of the tumor suppressor protein p53 by a lysine acetyltransferase (KAT), there has been a surge in the identification ...

Hat1p and Hat2p are the two subunits of a type B histone acetyltransferase from Saccharomyces cerevisiae that acetylates free histone H4 on lysine 12 in vitro. However, the role for these gene products in chromatin function has been unclear, as deletions of the HAT1 and/or HAT2 gene displayed no obvious phenotype. We have now identified a role for Hat1p ...

Tumor suppressor HIC1 (hypermethylated in cancer 1) is a gene that is essential for mammalian development, epigenetically silenced in many human tumors, and involved in a complex pathway regulating P53 tumor suppression activity. HIC1 encodes a sequence-specific transcriptional repressor containing five Kr�ppel-like C₂H₂ zinc fingers and an ...

Figure 3: Scheme illustrating the regulation of FoxO transcription factors and their potential role in the atrophy program. Legend:AKT is activated by growth factors and by physical activity and phosphorylates FoxO, inducing its translocation from the nucleus to the cytoplasm. Conversely, AMPK phosphorylates FoxO, increasing its transcriptional activity. Various other activators of FoxO are also ...

Previously we have shown that the presence of 3-nitrotyrosine within a peptide sequence severely depletes the peptide backbone fragments typically observed following electron capture dissociation (ECD) mass spectrometry. Instead, ECD of nitrated peptides is characterised by abundant losses of small neutrals (hydroxyl radicals, water and ammonia). Here, we investigate the origin of ammonia loss by ...

In eukaryotic cell nuclei, chromatin states dictated by different combinations of post-translational modifications of histones, such as acetylation, methylation and monoubiquitination of lysine residues, are part of the multitude of epigenomes involved in the fine-tuning of all genetic functions and in particular transcription. During ...

Histone deacetylases (HDACs) remove an acetyl group from lysine residues of target proteins to regulate cellular processes. Small-molecule inhibitors of HDACs cause cellular growth arrest, differentiation and/or apoptosis, and some are used clinically as anticancer drugs. In animal models, HDAC inhibitors are therapeutic for several ...

Proteins can be acetylated at the alpha-amino group of the N-terminal amino acid (methionine or the penultimate amino acid after methionine removal) or at the epsilon-amino group of internal lysines. In eukaryotes the majority of proteins are N-terminally acetylated, while this is extremely rare in bacteria. A variety of studies about ...

BackgroundNF-?B regulates the expression of a large number of target genes involved in the immune and inflammatory response, apoptosis, cell proliferation, differentiation and survival. We have earlier reported that p65, a subunit of NF-?B, is acetylated in vitro and in vivo at three different lysines (K310, K314 and K315) by the histone acetyltransferase ...

Methylation of histone H3 lysine 4 (H3K4me) is an evolutionarily conserved modification whose role in the regulation of gene expression has been extensively studied. In contrast, the function of H3K4 acetylation (H3K4ac) has received little attention because of a lack of tools to separate its function from that of H3K4me. Here we show that, in addition to ...

Rats were exposed to whole-body x radiation and killed at intervals of 2, 12, and 24 h later. Histones were separated from purified nuclei of liver cells. The intensity of histone acetylation was assessed according to incorporation of acetyl groups from /sup 14/CH/sub 3/COOH injected intraperitoneally. A graph is presented to show intensity of ...

6-N-(3-/sup 3/H)Trimethyl-DL-lysine was synthesized from 6-N-acetyl-L-lysine by the following chemical scheme: 6-N-acetyl-L-lysine ..-->.. 2-keto-6-N-acetylcaproic acid ..-->.. 2-(3-/sup 3/H)keto-6-N-acetylcaproic acid ..-->.. 2-(3-/sup 3/H)keto-6-N-acetylcaproic acid oxime ..-->.. 6-N-(3-/sup ...

Butyrate, a known histone deacetylase inhibitor (HDACi) and product of fibre fermentation, is postulated to mediate the protective effect of dietary fibre against colon cancer. The transcription factor Sp1 is a target of acetylation and is known to be associated with class I HDACs, including HDAC1. Sp1 is a ubiquitous transcription factor and Sp1-regulated genes include those ...

We report here that the MYST histone acetyltransferase HBO1 (histone acetyltransferase bound to ORC; MYST2/KAT7) is essential for postgastrulation mammalian development. Lack of HBO1 led to a more than 90% reduction of histone 3 lysine 14 (H3K14) acetylation, whereas no reduction of acetylation was detected at other histone ...