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Acetylation (or in IUPAC nomenclature ethanoylation) is an organic esterification reaction with acetic acid. It introduces an acetyl functional group into a chemical compound. Such compounds are termed acetate esters or acetates. Deacetylation is the opposite reaction, the removal of an acetyl group from a chemical compound.

Acetylation of wood

Since the beginning of the 20th century, acetylation of wood was researched as a method to upgrade the durability of wood in resistance against rotting processes and molds. Secondary benefits include the improvement of dimensional stability, improved surface hardness, and no decrease in mechanical properties due to the treatment.

The physical properties of any material are determined by its chemical structure. Wood contains an abundance of chemical groups called free hydroxyls. Free hydroxyl groups adsorb and release water according to changes in the climatic conditions to which the wood is exposed. This is an explanation as to why wood swells and shrinks. It is also believed that the digestion of wood by enzymes initiates at the free hydroxyl sites – which is one of the principal reasons why wood is prone to decay.

Acetylation changes the free hydroxyls within the wood into acetyl groups. This is done by reacting the wood with acetic anhydride, which comes from acetic acid (known as vinegar when in its dilute form). When the free hydroxyl group is transformed to an acetyl group, the ability of the wood to absorb water is greatly reduced, rendering the wood more dimensionally stable and, because it is no longer digestible, extremely durable.

In 2007, Titan Wood, a London-based company, with production facilities in The Netherlands, achieved cost-effective commercialization and began large-scale production of acetylated wood under the trade name "Accoya".

References

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 [[File:aspirin synthesis.png|thumb|400px|[[Salicylic acid]] is acetylated to form [[aspirin]]]]
 '''Acetylation''' (or in [[IUPAC nomenclature]] '''ethanoylation''') is an organic [[esterification]] reaction with [[acetic acid]]. It introduces an [[acetyl]] [[functional group]] into a [[chemical compound]]. Such compounds are termed acetate esters or acetates. '''Deacetylation''' is the opposite reaction, the removal of an acetyl group from a chemical compound.
-Both acetylation and deacetylation reactions occur within living cells as [[drug metabolism]], by enzymes in the liver and other organs (e. g., the brain). Pharmaceuticals frequently employ acetylation to enable such esters to cross the [[blood-brain barrier]] (and [[placenta]]), where they are deacetylated by enzymes ([[carboxylesterase]]s) in a manner similar to [[acetylcholine]]. Examples of acetylated pharmaceuticals are [[diacetylmorphine]] (heroin), [[acetylsalicylic acid]] (aspirin), [[THC-O-acetate]], and [[diacerein]]. Conversely, drugs such as [[isoniazid]] are acetylated within the liver during drug metabolism. A drug that depends on such metabolic transformations in order to act is termed a [[prodrug]].
-For esterification reactions outside of cells, [[acetic anhydride]] is commonly used.
-== Protein acetylation ==
-Acetylation is an important modification of proteins in [[cell (biology)|cell biology]]; and proteomics studies have identified thousands of acetylated mammalian proteins.<ref>{{cite journal | vauthors = Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M | s2cid = 206520776 | title = Lysine acetylation targets protein complexes and co-regulates major cellular functions | journal = Science | volume = 325 | issue = 5942 | pages = 834–840 | year = 2009 | pmid = 19608861 | doi = 10.1126/science.1175371 | bibcode = 2009Sci...325..834C }}</ref><ref>{{cite journal | vauthors = Fritz KS, Galligan JJ, Hirschey MD, Verdin E, Petersen DR | title = Mitochondrial acetylome analysis in a mouse model of alcohol-induced liver injury utilizing SIRT3 knockout mice | journal = J. Proteome Res. | volume = 11 | issue = 3 | pages = 1633–1643 | year = 2012 | pmid = 22309199 | pmc = 3324946 | doi = 10.1021/pr2008384 }}</ref><ref>{{cite web| vauthors = Brook T |title=Protein Acetylation: Much More than Histone Acetylation |url=https://www.caymanchem.com/app/template/Article.vm/article/2152 |publisher=Cayman Chemical |url-status=dead |archive-url=https://web.archive.org/web/20140228141824/https://www.caymanchem.com/app/template/Article.vm/article/2152 |archive-date=2014-02-28 }}</ref> Acetylation occurs as a co-translational and [[post-translational modification]] of [[protein]]s, for example, [[histone]]s, [[p53]], and [[tubulin]]s. Among these proteins, [[chromatin]] proteins and metabolic enzymes are highly represented, indicating that acetylation has a considerable impact on [[gene expression]] and [[metabolism]]. In [[bacteria]], 90% of proteins involved in central metabolism of ''[[Salmonella enterica]]'' are acetylated.<ref>{{cite journal | vauthors = Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL | title = Regulation of cellular metabolism by protein lysine acetylation | journal = Science | volume = 327 | issue = 5968 | pages = 1000–1004 | year = 2010 | pmid = 20167786 | pmc = 3232675 | doi = 10.1126/science.1179689 | bibcode = 2010Sci...327.1000Z | first3 = Wenqing }}</ref><ref>{{cite journal | vauthors = Wang Q, Zhang Y, Yang C, Xiong H, Lin Y, Yao J, Li H, Xie L, Zhao W, Yao Y, Ning ZB, Zeng R, Xiong Y, Guan KL, Zhao S, Zhao GP | display-authors = 6 | title = Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux | journal = Science | volume = 327 | issue = 5968 | pages = 1004–7 | date = February 2010 | pmid = 20167787 | pmc = 4183141 | doi = 10.1126/science.1179687 | bibcode = 2010Sci...327.1004W }}</ref>
-=== N-terminal acetylation===
-[[File:Protein-acetylation-nterminal.svg|thumb|450px|N-terminal acetylation by [[N-terminal acetyltransferase]]s (NATs).]]
-[[N-terminal]] acetylation is one of the most common co-translational covalent modifications of proteins in [[eukaryotes]], and it is crucial for the regulation and function of different proteins. N-terminal acetylation plays an important role in the synthesis, stability and localization of proteins. About 85% of all human proteins and 68% in [[yeast]] are acetylated at their Nα-terminus.<ref name="Van Damme e1002169">{{cite journal | vauthors = Van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J, Martinho RG, Gevaert K, Arnesen T | title = NatF contributes to an evolutionary shift in protein N-terminal acetylation and is important for normal chromosome segregation | journal = PLOS Genet. | volume = 7 | issue = 7 | pages = e1002169 | year = 2011 | pmid = 21750686 | pmc = 3131286 | doi = 10.1371/journal.pgen.1002169 }}</ref> Several proteins from [[prokaryotes]] and [[archaea]] are also modified by N-terminal acetylation.
-N-terminal Acetylation is catalyzed by a set of enzyme complexes, the [[N-terminal acetyltransferase]]s (NATs). NATs transfer an acetyl group from [[acetyl-coenzyme A]] (Ac-CoA) to the α-amino group of the first [[amino acid]] residue of the protein. Different NATs are responsible for the acetylation of nascent protein N-terminal, and the acetylation was found to be irreversible so far.<ref>{{cite journal | vauthors = Starheim KK, Gevaert K, Arnesen T | title = Protein N-terminal acetyltransferases: when the start matters | journal = Trends Biochem. Sci. | volume = 37 | issue = 4 | pages = 152–161 | year = 2012 | pmid = 22405572 | doi = 10.1016/j.tibs.2012.02.003 }}</ref>
-==== N-terminal acetyltransferases ====
-To date, seven different NATs have been found in humans - NatA, NatB, NatC, NatD, NatE, NatF and NatH. Each of these different enzyme complexes is specific for different amino acids or amino acid sequences which is shown in the following table.
-'''Table 1. The Composition and Substrate specificity of NATs.'''
-{| class="wikitable"
-|-
-! NAT!! Subunits (catalytic subunits are in '''bold'''.) !! Substrates
-|-
-| NatA|| '''[[N-alpha-acetyltransferase 10|Naa10]]''' (Ard1) Naa15 (Nat1) || [[serine|Ser]]-, [[alanine|Ala]]-, [[glycine|Gly]]-, Thr-, [[valine|Val]]-, [[cysteine|Cys]]- [[N-termini]]
-|-
-| NatB || '''[[NAA20 (gene)|Naa20]]''' (Nat3) Naa25 (Mdm20) || [[methionine|Met]]-[[glutamic acid|Glu]]-, [[methionine|Met]]-[[Aspartic acid|Asp]]-, [[methionine|Met]]-[[Asparagine|Asn]]-, [[methionine|Met]]-[[glutamine|Gln]]- [[N-termini]]
-|-
-| NatC || '''Naa30''' (Mak3) Naa35 (Mak10) Naa38 (Mak31) || [[methionine|Met]]-[[leucine|Leu]]-, [[methionine|Met]]-Ile-, [[methionine|Met]]-Trp-, [[methionine|Met]]-[[phenylalanine|Phe]]- [[N-termini]]
-|-
-| NatD || '''Naa40''' (Nat4) || [[serine|Ser]]-[[glycine|Gly]]-[[glycine|Gly]]-, [[serine|Ser]]-[[glycine|Gly]]-[[arginine|Arg]]- [[N-termini]]
-|-
-| NatE || '''Naa50''' (Nat5) Naa10 (Ard1) Naa15 (Nat1)  || [[methionine|Met]]-Leu-, [[methionine|Met]]-[[alanine|Ala]]-, [[methionine|Met]]-[[lysine|Lys]]-, [[methionine|Met]]-[[methionine|Met]]- [[N-termini]]
-|-
-| NatF || '''Naa60''' || [[methionine|Met]]-[[lysine|Lys]]-, [[methionine|Met]]-[[leucine|Leu]]-, [[methionine|Met]]-Ile-, [[methionine|Met]]-Trp-, [[methionine|Met]]-[[Phenylalanine|Phe]]- [[N-termini]]
-|-
-| NatH || '''Naa80''' || [[Actin]]- [[N-termini]]
-|}
-===== NatA =====
-[[File:NatA.png|alt=|thumb|317x317px|Crystal structure of the NatA complex (Naa10 and Naa15) from ''[[Schizosaccharomyces pombe]]''. The green chains represent the auxiliary subunit Naa15 and the cyan chains the catalytic subunit Naa10.<ref name="pmid23912279">{{cite journal | vauthors = Liszczak G, Goldberg JM, Foyn H, Petersson EJ, Arnesen T, Marmorstein R | title = Molecular basis for N-terminal acetylation by the heterodimeric NatA complex | journal = Nat. Struct. Mol. Biol. | volume = 20 | issue = 9 | pages = 1098–105 | year = 2013 | pmid = 23912279 | pmc = 3766382 | doi = 10.1038/nsmb.2636 }}</ref> (PDB ID: [http://www.rcsb.org/structure/4KVM 4KVM])]]
-NatA is composed of two subunits, the catalytic [[Protein subunit|subunit]] Naa10 and the auxiliary subunit Naa15. NatA subunits are more complex in higher [[eukaryotes]] than in lower eukaryotes. In addition to the genes ''NAA10'' and ''NAA15'', the mammal-specific genes ''NAA11'' and ''NAA16'', make functional gene products, which form different active NatA complexes. Four possible hNatA catalytic-auxiliary dimers are formed by these four proteins. However, Naa10/Naa15 is the most abundant NatA.<ref>{{cite journal | vauthors = Starheim KK, Gromyko D, Velde R, Varhaug JE, Arnesen T | title = Composition and biological significance of the human Nalpha-terminal acetyltransferases | journal = BMC Proceedings | volume = 3 Suppl 6 | issue = Suppl 6 | pages = S3 | year = 2009 | pmid = 19660096 | pmc = 2722096 | doi = 10.1186/1753-6561-3-s6-s3 }}</ref>
-NatA acetylates [[serine|Ser]], [[alanine|Ala]]-, [[glycine|Gly]]-, Thr-, [[valine|Val]]- and [[cysteine|Cys]] [[N-termini]] after the initiator [[methionine]] is removed by methionine amino-peptidases. These amino acids are more frequently expressed in the N-terminal of proteins in eukaryotes, so NatA is the major NAT corresponding to the whole number of its potential substrates.<ref>{{cite journal | vauthors = Arnesen T, Van Damme P, Polevoda B, Helsens K, Evjenth R, Colaert N, Varhaug JE, Vandekerckhove J, Lillehaug JR, Sherman F, Gevaert K | title = Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 106 | issue = 20 | pages = 8157–8162 | year = 2009 | pmid = 19420222 | doi = 10.1073/pnas.0901931106 | bibcode = 2009PNAS..106.8157A | first3 = Bogdan | pmc=2688859| doi-access = free }}</ref>
-Several different interaction partners are involved in the N-terminal acetylation by NatA. Huntingtin interacting protein K (HYPK) interacts with hNatA on the [[ribosome]] to affect the N-terminal acetylation of a subset of NatA substrates. Subunits hNaa10 and hNaa15 will increase the tendency for aggregation of Huntingtin if HYPK is depleted. [[Hypoxia-inducible factor]] (HIF)-1α has also been found to interact with hNaa10 to inhibit hNaa10-mediated activation of β-catenin transcriptional activity.<ref>{{cite journal | vauthors = Arnesen T, Starheim KK, Van Damme P, Evjenth R, Dinh H, Betts MJ, Ryningen A, Vandekerckhove J, Gevaert K, Anderson D | title = The chaperone-like protein HYPK acts together with NatA in cotranslational N-terminal acetylation and prevention of Huntingtin aggregation | journal = Mol. Cell. Biol. | volume = 30 | issue = 8 | pages = 1898–1909 | year = 2010 | pmid = 20154145 | pmc = 2849469 | doi = 10.1128/mcb.01199-09 }}</ref>
-===== NatB =====
-NatB complexes are composed of the catalytic subunit Naa20p and the auxiliary subunit Naa25p, which are both found in yeast and humans. In [[yeast]], all the NatB subunits are ribosome-associated; but in humans, NatB subunits are both found to be ribosome-associated and non-ribosomal form. NatB acetylates the N-terminal methionine of substrates starting with [[methionine|Met]]-[[glutamic acid|Glu]]-, [[methionine|Met]]-[[aspartic acid|Asp]]-, [[methionine|Met]]-[[asparagine|Asn]]- or [[methionine|Met]]-[[glutamine|Gln]]- N termini.
-===== NatC =====
-NatC complex consists of one catalytic subunit Naa30p and two auxiliary subunits Naa35p and Naa38p. All three subunits are found on the ribosome in yeast, but they are also found in non-ribosomal NAT forms like Nat2. NatC complex acetylates the N-terminal methionine of substrates [[methionine|Met]]-[[leucine|Leu]]-, [[methionine|Met]]-Ile-, [[methionine|Met]]-Trp- or [[methionine|Met]]-[[phenylalanine|Phe]] N-termini.
-===== NatD =====
-NatD is only composed with the catalytic unit Naa40p and Naa40p and it is conceptually different form the other NATs. At first, only two substrates, H2A and H4 have been identified in yeast and humans. Secondly, the substrate specificity of Naa40p lies within the first 30-50 residues which are quite larger than the substrate specificity of other NATs. The acetylation of histones by NatD is partially associate with ribosomes and the amino acids substrates are the very N-terminal residues, which makes it different from [[lysine N-acetyltransferase]]s (KATs).<ref>{{cite journal | vauthors = Hole K, Van Damme P, Dalva M, Aksnes H, Glomnes N, Varhaug JE, Lillehaug JR, Gevaert K, Arnesen T | title = The human N-alpha-acetyltransferase 40 (hNaa40p/hNatD) is conserved from yeast and N-terminally acetylates histones H2A and H4 | journal = PLOS ONE | volume = 6 | issue = 9 | pages = e24713 | year = 2011 | pmid = 21935442 | pmc = 3174195 | doi = 10.1371/journal.pone.0024713 | bibcode = 2011PLoSO...624713H | doi-access = free }}</ref>
-===== NatE =====
-NatE complex consists with subunit Naa50p and two NatA subunits, Naa10p and Naa15p. The N terminus of Naa50p substrates is different from those acetylated by the NatA activity of Naa10p.<ref>{{cite journal | vauthors = Gautschi M, Just S, Mun A, Ross S, Rücknagel P, Dubaquié Y, Ehrenhofer-Murray A, Rospert S | display-authors = 6 | title = The yeast N(alpha)-acetyltransferase NatA is quantitatively anchored to the ribosome and interacts with nascent polypeptides | journal = Molecular and Cellular Biology | volume = 23 | issue = 20 | pages = 7403–14 | date = October 2003 | pmid = 14517307 | pmc = 230319 | doi = 10.1128/mcb.23.20.7403-7414.2003 }}</ref> NAA50 in plants is essential to control plant growth, development, and stress responses and NAA50 function is highly conserved between humans and plants.<ref>{{cite journal | vauthors = Hartman S | title = The Meaning of an End: N-Terminal Acetyltransferase NAA50 Controls Plant Growth and Stress Responses | journal = Plant Physiology | volume = 183 | issue = 4 | pages = 1410–1411 | date = August 2020 | pmid = 32747486 | doi = 10.1104/pp.20.00794 | pmc = 7401126 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Armbruster L, Linster E, Boyer JB, Brünje A, Eirich J, Stephan I, Bienvenut WV, Weidenhausen J, Meinnel T, Hell R, Sinning I, Finkemeier I, Giglione C, Wirtz M | display-authors = 6 | title = NAA50 Is an Enzymatically Active ''N''<sup>α</sup>-Acetyltransferase That Is Crucial for Development and Regulation of Stress Responses | journal = Plant Physiology | volume = 183 | issue = 4 | pages = 1502–1516 | date = August 2020 | pmid = 32461302 | doi = 10.1104/pp.20.00222 | pmc = 7401105 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Neubauer M, Innes RW | title = Loss of the Acetyltransferase NAA50 Induces Endoplasmic Reticulum Stress and Immune Responses and Suppresses Growth | journal = Plant Physiology | volume = 183 | issue = 4 | pages = 1838–1854 | date = August 2020 | pmid = 32457093 | doi = 10.1104/pp.20.00225 | pmc = 7401112 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Feng J, Hu J, Li Y, Li R, Yu H, Ma L | title = The N-Terminal Acetyltransferase Naa50 Regulates Arabidopsis Growth and Osmotic Stress Response | journal = Plant & Cell Physiology | volume = 61 | issue = 9 | pages = 1565–1575 | date = September 2020 | pmid = 32544241 | doi = 10.1093/pcp/pcaa081 }}</ref>
-===== NatF =====
-[[File:5hh0.jpg|thumb|270px|NatF dimer, Human]]
-NatF is a NAT that is composed of the Naa60 enzyme. Initially, it was thought that NatF was only found in higher eukaryotes, since it was absent from yeast.<ref>{{cite journal | vauthors = Van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J, Martinho RG, Gevaert K, Arnesen T | display-authors = 6 | title = NatF contributes to an evolutionary shift in protein N-terminal acetylation and is important for normal chromosome segregation | journal = PLOS Genetics | volume = 7 | issue = 7 | pages = e1002169 | date = July 2011 | pmid = 21750686 | pmc = 3131286 | doi = 10.1371/journal.pgen.1002169 }}</ref> However, it was later found that Naa60 is found throughout the eukaryotic domain, but was secondarily lost in the fungi lineage.<ref>{{cite journal | vauthors = Rathore OS, Faustino A, Prudêncio P, Van Damme P, Cox CJ, Martinho RG | title = Absence of N-terminal acetyltransferase diversification during evolution of eukaryotic organisms | journal = Scientific Reports | volume = 6 | pages = 21304 | date = February 2016 | pmid = 26861501 | pmc = 4748286 | doi = 10.1038/srep21304 | bibcode = 2016NatSR...621304R }}</ref>  Compared to yeast, NatF contributes to the higher abundance of N-terminal acetylation in humans. NatF complex acetylates the N-terminal methionine of substrates [[methionine|Met]]-[[lysine|Lys]]-, [[methionine|Met]]-[[leucine|Leu]]-, [[methionine|Met]]-Ile-, [[methionine|Met]]-Trp- and [[methionine|Met]]-[[phenylalanine|Phe]] N termini which are partly overlapping with NatC and NatE.<ref name="Van Damme e1002169"/> NatF has been shown to have an organellar localization and acetylates cytosolic N-termini of transmembrane proteins.<ref>{{cite journal | vauthors = Aksnes H, Van Damme P, Goris M, Starheim KK, Marie M, Støve SI, Hoel C, Kalvik TV, Hole K, Glomnes N, Furnes C, Ljostveit S, Ziegler M, Niere M, Gevaert K, Arnesen T | display-authors = 6 | title = An organellar nα-acetyltransferase, naa60, acetylates cytosolic N termini of transmembrane proteins and maintains Golgi integrity | journal = Cell Reports | volume = 10 | issue = 8 | pages = 1362–74 | date = March 2015 | pmid = 25732826 | doi = 10.1016/j.celrep.2015.01.053 | doi-access = free }}</ref> The organellar localization of Naa60 is mediated by its unique C-terminus, which consists of two alpha helices that peripherally associate with the membrane and mediate interactions with [[Phosphatidylinositol|PI(4)P]].<ref>{{cite journal | vauthors = Aksnes H, Goris M, Strømland Ø, Drazic A, Waheed Q, Reuter N, Arnesen T | title = Molecular determinants of the N-terminal acetyltransferase Naa60 anchoring to the Golgi membrane | journal = The Journal of Biological Chemistry | volume = 292 | issue = 16 | pages = 6821–6837 | date = April 2017 | pmid = 28196861 | pmc = 5399128 | doi = 10.1074/jbc.M116.770362 | doi-access = free }}</ref>
-===== NAA80/NatH =====
-NAA80/NatH is an N-terminal acetyltransferase that specifically acetylates the N-terminus of [[actin]].<ref>{{cite journal | vauthors = Drazic A, Aksnes H, Marie M, Boczkowska M, Varland S, Timmerman E, Foyn H, Glomnes N, Rebowski G, Impens F, Gevaert K, Dominguez R, and Arnesen T| title = NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility | journal = Proc Natl Acad Sci U S A | volume = 115 | issue = 17 | pages = 4399–4404 | year = 2018 | pmid = 29581253 | pmc = 5924898  | doi = 10.1073/pnas.1718336115| doi-access = free }}</ref>
-==== N-terminal acetylation function ====
-===== Protein stability =====
-N-terminal acetylation of proteins can affect protein stability, but the results and mechanism were not very clear until now.<ref name="pmid22718636">{{cite journal | vauthors = Hollebeke J, Van Damme P, Gevaert K | title = N-terminal acetylation and other functions of Nα-acetyltransferases | journal = Biol. Chem. | volume = 393 | issue = 4 | pages = 291–8 | year = 2012 | pmid = 22718636 | doi = 10.1515/hsz-2011-0228 | s2cid = 40566358 }}</ref> It was believed that N-terminal acetylation protects proteins from being degraded as Nα-acetylation N-termini were supposed to block N-terminal ubiquitination and subsequent [[protein degradation]].<ref name="pmid6095265">{{cite journal | vauthors = Hershko A, Heller H, Eytan E, Kaklij G, Rose IA | title = Role of the alpha-amino group of protein in ubiquitin-mediated protein breakdown | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 81 | issue = 22 | pages = 7021–5 | year = 1984 | pmid = 6095265 | pmc = 392068 | doi = 10.1073/pnas.81.22.7021 | bibcode = 1984PNAS...81.7021H | doi-access = free }}</ref> However, several studies have shown that the N-terminal acetylated protein have a similar degradation rate as proteins with a non-blocked N-terminus.<ref>{{cite journal | vauthors = Hwang CS, Shemorry A, Varshavsky A | title = N-terminal acetylation of cellular proteins creates specific degradation signals | journal = Science | volume = 327 | issue = 5968 | pages = 973–977 | year = 2010 | pmid = 20110468 | doi = 10.1126/science.1183147 | bibcode = 2010Sci...327..973H | pmc = 4259118 }}</ref>
-===== Protein localization =====
-N-terminal acetylation has been shown that it can steer the localization of proteins. Arl3p is one of the ‘Arf-like’ (Arl) [[GTPases]], which is crucial for the organization of membrane traffic.<ref>{{cite journal | vauthors = Behnia R, Panic B, Whyte JR, Munro S | title = Targeting of the Arf-like GTPase Arl3p to the Golgi requires N-terminal acetylation and the membrane protein Sys1p | journal = Nat. Cell Biol. | volume = 6 | issue = 5 | pages = 405–413 | year = 2004 | pmid = 15077113 | doi = 10.1038/ncb1120 | s2cid = 22954283 }}</ref> It requires its Nα-acetyl group for its targeting to the Golgi membrane by the interaction with Golgi membrane-residing protein Sys1p. If the [[phenylalanine|Phe]] or Tyr is replaced by an [[alanine|Ala]] at the N-terminal of Arl3p, it can no longer localized to the Golgi membrane, indicating that Arl3p needs its natural N-terminal residues which could be acetylated for proper localization.<ref>{{cite journal | vauthors = Starheim KK, Gromyko D, Evjenth R, Ryningen A, Varhaug JE, Lillehaug JR, Arnesen T | title = Knockdown of human N alpha-terminal acetyltransferase complex C leads to p53-dependent apoptosis and aberrant human Arl8b localization | journal = Mol. Cell. Biol. | volume = 29 | issue = 13 | pages = 3569–3581 | year = 2009 | pmid = 19398576 | pmc = 2698767 | doi = 10.1128/mcb.01909-08 }}</ref>
-===== Metabolism and apoptosis =====
-Protein N-terminal acetylation has also been proved to relate with cell cycle regulation and apoptosis with protein knockdown experiments. Knockdown of the NatA or the NatC complex leads to the induction of [[p53]]-dependent [[apoptosis]], which may indicate that the anti-apoptotic proteins were less or no longer functional because of reduced protein N-terminal acetylation.<ref>{{cite journal | vauthors = Gromyko D, Arnesen T, Ryningen A, Varhaug JE, Lillehaug JR | title = Depletion of the human Nα-terminal acetyltransferase A induces p53-dependent apoptosis and p53-independent growth inhibition | journal = Int. J. Cancer | volume = 127 | issue = 12 | pages = 2777–2789 | year = 2010 | pmid = 21351257 | doi = 10.1002/ijc.25275 | doi-access = free }}</ref> But in contrast, the [[caspase-2]], which is acetylated by NatA, can interact with the adaptor protein RIP associated Ich-1/Ced-3 homologous protein with a death domain (RAIDD). This could activate caspase-2 and induce [[cell apoptosis]].<ref>{{cite journal | vauthors = Yi CH, Pan H, Seebacher J, Jang IH, Hyberts SG, Heffron GJ, Vander Heiden MG, Yang R, Li F, Locasale JW, Sharfi H, Zhai B, Rodriguez-Mias R, Luithardt H, Cantley LC, Daley GQ, Asara JM, Gygi SP, Wagner G, Liu CF, Yuan J | title = Metabolic regulation of protein N-alpha-acetylation by Bcl-xL promotes cell survival | journal = Cell | volume = 146 | issue = 4 | pages = 607–620 | year = 2011 | pmid = 21854985 | pmc = 3182480 | doi = 10.1016/j.cell.2011.06.050 }}</ref>
-===== Protein synthesis =====
-[[Ribosome]] proteins play an important role in the protein synthesis, which could also be N-terminal acetylated. The N-terminal acetylation of the ribosome proteins may have an effect on protein synthesis. A decrease of 27% and 23% in the protein synthesis rate was observed with NatA and NatB deletion strains. A reduction of translation fidelity was observed in the NatA deletion strain and a defect in ribosome was noticed in the NatB deletion strain.<ref>{{cite journal | vauthors = Kamita M, Kimura Y, Ino Y, Kamp RM, Polevoda B, Sherman F, Hirano H | title = N(α)-Acetylation of yeast ribosomal proteins and its effect on protein synthesis | journal = J Proteomics | volume = 74 | issue = 4 | pages = 431–441 | year = 2011 | pmid = 21184851 | doi = 10.1016/j.jprot.2010.12.007 }}</ref>
-==== Cancer ====
-NATs have been suggested to act as both onco-proteins and tumor suppressors in human cancers, and NAT expression may be increased and decreased in cancer cells. Ectopic expression of hNaa10p increased [[cell proliferation]] and up regulation of gene involved in cell survival proliferation and [[metabolism]]. Overexpression of hNaa10p was in the urinary [[bladder cancer]], [[breast cancer]] and [[cervical cancer|cervical carcinoma]].<ref name="pmid19287988">{{cite journal | vauthors = Yu M, Gong J, Ma M, Yang H, Lai J, Wu H, Li L, Li L, Tan D | title = Immunohistochemical analysis of human arrest-defective-1 expressed in cancers in vivo | journal = Oncol. Rep. | volume = 21 | issue = 4 | pages = 909–15 | year = 2009 | pmid = 19287988 | doi = 10.3892/or_00000303 | doi-access = free }}</ref> But a high level expression of hNaa10p could also suppress tumor growth and a reduced level of expressed hNaa10p is associated with a poor prognosis, large tumors and more lymph node metastases.
-'''Table 2. Overview of the expression of NatA subunits in various cancer tissues'''<ref>{{cite journal | vauthors = Kalvik TV, Arnesen T | title = Protein N-terminal acetyltransferases in cancer | journal = Oncogene | volume = 32 | issue = 3 | pages = 269–276 | year = 2013 | pmid = 22391571 | doi = 10.1038/onc.2012.82 | doi-access = free }}</ref>
-{| class="wikitable"
-|-
-! Nat subunits !! Cancer tissue !! Expression pattern
-|-
-| hNaa10 || [[lung cancer]], [[breast cancer]], [[colorectal cancer]], [[hepatocellular carcinoma]] || high in tumors
-|-
-| hNaa10 || [[lung cancer]], [[breast cancer]], [[pancreatic cancer]], [[ovarian cancer]] || loss of heterozygosity in tumors
-|-
-| hNaa10 || [[breast cancer]], [[gastric cancer]], [[lung cancer]] || high in primary tumors, but low with lymph node metastases
-|-
-| hNaa10 || [[Non-small cell lung cancer]] || low in tumors
-|-
-| hNaa15 || [[papillary thyroid carcinoma]], [[gastric cancer]] || high in tumors
-|-
-| hNaa15 || [[neuroblastoma]] || high in advanced stage tumors
-|-
-| hNaa11 || [[hepatocellular carcinoma]] || loss of heterozygosity in tumors
-|}
-=== Lysine acetylation and deacetylation ===
-[[File:Lysine acetylation.svg|thumb|400px|Lysine acetylation]]
-Proteins are typically acetylated on [[lysine]] residues and this reaction relies on [[acetyl-CoA|acetyl-coenzyme A]] as the acetyl group donor.
-In [[histone acetylation and deacetylation]], histone proteins are acetylated and deacetylated on lysine residues in the N-terminal tail as part of [[gene regulation]]. Typically, these reactions are catalyzed by [[enzyme]]s with ''[[histone acetyltransferase]]'' (HAT) or ''[[histone deacetylase]]'' (HDAC) activity, although HATs and HDACs can modify the acetylation status of non-histone proteins as well.<ref name="pmid17681659">{{cite journal | vauthors = Sadoul K, Boyault C, Pabion M, Khochbin S | title = Regulation of protein turnover by acetyltransferases and deacetylases | journal = Biochimie | volume = 90 | issue = 2 | pages = 306–12 | year = 2008 | pmid = 17681659 | doi = 10.1016/j.biochi.2007.06.009 }}</ref>
-The regulation of transcription factors, effector proteins, [[molecular chaperones]], and cytoskeletal proteins by acetylation and deacetylation is a significant post-translational regulatory mechanism<ref name="pmid16289629 ">{{cite journal | vauthors = Glozak MA, Sengupta N, Zhang X, Seto E | title = Acetylation and deacetylation of non-histone proteins | journal = Gene | volume = 363 | pages = 15–23 | year = 2005 | pmid = 16289629 | doi = 10.1016/j.gene.2005.09.010 }}</ref> These regulatory mechanisms are analogous to phosphorylation and dephosphorylation by the action of [[protein kinase|kinases]] and [[phosphatases]]. Not only can the acetylation state of a protein modify its activity but there has been recent suggestion that this post-translational modification may also crosstalk with [[phosphorylation]], [[methylation]], [[ubiquitination]], sumoylation, and others for dynamic control of cellular signaling.<ref name="pmid18722172">{{cite journal | vauthors = Yang XJ, Seto E | title = Lysine acetylation: codified crosstalk with other posttranslational modifications | journal = Mol. Cell | volume = 31 | issue = 4 | pages = 449–61 | year = 2008 | pmid = 18722172 | pmc = 2551738 | doi = 10.1016/j.molcel.2008.07.002 }}</ref> The regulation of [[tubulin]] protein is an example of this in mouse neurons and astroglia.<ref name=Edde89>{{cite journal | vauthors = Eddé B, Denoulet P, de Néchaud B, Koulakoff A, Berwald-Netter Y, Gros F | title = Posttranslational modifications of tubulin in cultured mouse brain neurons and astroglia | journal = Biol. Cell | volume = 65 | issue = 2 | pages = 109–117 | year = 1989 | pmid = 2736326 | doi = 10.1016/0248-4900(89)90018-x | first3 = B }}</ref><ref>{{cite journal | vauthors = Maruta H, Greer K, Rosenbaum JL | title = The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules | journal = J. Cell Biol. | volume = 103 | issue = 2 | pages = 571–579 | year = 1986 | pmid = 3733880 | pmc = 2113826 | doi = 10.1083/jcb.103.2.571 }}</ref> A ''tubulin acetyltransferase'' is located in the [[axoneme]], and acetylates the α-tubulin subunit in an assembled microtubule. Once disassembled, this acetylation is removed by another specific deacetylase in the cell cytosol. Thus axonemal microtubules, which have a long half-life, carry a "signature acetylation," which is absent from cytosolic microtubules that have a shorter half-life.
-In the field of [[epigenetic]]s, [[histone acetylation]] (and [[deacetylation]]) have been shown to be important mechanisms in the regulation of gene transcription. Histones, however, are not the only proteins regulated by [[posttranslational]] acetylation. The following are examples of various other proteins with roles in regulating signal transduction, whose activities are also affected by acetylation and deacetylation.
-==== p53 ====
-The [[p53]] protein is a [[tumor suppressor]] that plays an important role in the signal transactions in cells, especially in maintaining the stability of the [[genome]] by preventing mutation. Therefore, it is also known as “the guardian of the genome". It also regulates the [[cell cycle]] and arrests cell growth by activating a regulator of the cell cycle, [[p21]]. Under severe [[DNA damage]], it also initiates [[programmed cell death]].The function of [[p53]] is negatively regulated by [[oncoprotein]] [[Mdm2]]. Studies suggested that [[Mdm2]] will form a complex with [[p53]] and prevent it from binding to specific p53-responsive genes.<ref>{{cite book| vauthors = Alberts B |title=Molecular Biology of the Cell|date=March 2002|publisher=Garland Science|isbn=0815332181}}</ref><ref>{{cite book| vauthors = Weinberg RA |title=Biology of cancer.|year=2013|publisher=Garland Science|location=[S.l.]|isbn=978-0815342205|edition=2.}}</ref>
-===== Acetylation of p53 =====
-[[File:P53 acetylation site.png|thumb|400px|p53 acetylation site]]
-The acetylation of p53 is indispensable for its activation. It has been reported that the acetylation level of p53 will increase significantly when the cell undergoes stress. Acetylation sites have been observed on the DNA binding domain (K164 and K120) and the C terminus.<ref>{{cite journal | vauthors = Brooks CL, Gu W | title = The impact of acetylation and deacetylation on the p53 pathway | journal = Protein Cell | volume = 2 | issue = 6 | pages = 456–462 | year = 2011 | pmid = 21748595 | doi = 10.1007/s13238-011-1063-9 | pmc=3690542}}</ref> Acetylation sites demonstrate significant redundancy: if only one acetylation site is inactivated by mutation to arginine, the expression of [[p21]] is still observed. However, if multiple acetylation sites are blocked, the expression of [[p21]] and the suppression of cell growth caused by [[p53]] is completely lost. In addition, the acetylation of [[p53]] prevents its binding to the repressor [[Mdm2]] on DNA.<ref>{{cite journal | vauthors = Tang Y, Zhao W, Chen Y, Zhao Y, Gu W | title = Acetylation is indispensable for p53 activation | journal = Cell | volume = 133 | issue = 4 | pages = 612–626 | year = 2008 | pmid = 18485870 | pmc = 2914560 | doi = 10.1016/j.cell.2008.03.025 }}</ref> In addition, it is suggested that the p53 acetylation is crucial for its transcription-independent [[proapoptotic]] functions.<ref>{{cite journal | vauthors = Yamaguchi H, Woods NT, Piluso LG, Lee HH, Chen J, Bhalla KN, Monteiro A, Liu X, Hung MC, Wang HG | title = p53 acetylation is crucial for its transcription-independent proapoptotic functions | journal = J. Biol. Chem. | volume = 284 | issue = 17 | pages = 11171–11183 | year = 2009 | pmid = 19265193 | pmc = 2670122 | doi = 10.1074/jbc.M809268200 | doi-access = free }}</ref> An acetylation site of the C-terminus was investigated by [[Molecular dynamics|molecular dynamics simulations]] and [[circular dichroism spectroscopy]], and it was suggested that the acetylation changes the structural ensemble of the C-terminus.<ref>{{cite journal | vauthors = Iida S, Mashimo T, Kurosawa T, Hojo H, Muta H, Goto Y, Fukunishi Y, Nakamura H, Higo J | display-authors = 6 | title = Variation of free-energy landscape of the p53 C-terminal domain induced by acetylation: Enhanced conformational sampling | journal = Journal of Computational Chemistry | volume = 37 | issue = 31 | pages = 2687–2700 | date = December 2016 | pmid = 27735058 | pmc = 5242334 | doi = 10.1002/jcc.24494 }}</ref>
-===== Implications for cancer therapy =====
-Since the major function of [[p53]] is [[tumor suppressor]], the idea that activation of p53 is an appealing strategy for cancer treatment. [[Nutlin-3]]<ref>{{cite journal | vauthors = Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA | title = In vivo activation of the p53 pathway by small-molecule antagonists of MDM2 | journal = Science | volume = 303 | issue = 5659 | pages = 844–848 | year = 2004 | pmid = 14704432 | doi = 10.1126/science.1092472 | bibcode = 2004Sci...303..844V | s2cid = 16132757 }}</ref> is a small molecule designed to target [[p53]] and [[Mdm2]] interaction that kept [[p53]] from deactivation.<ref>{{cite journal | vauthors = Shangary S, Wang S | title = Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy | journal = Annu. Rev. Pharmacol. Toxicol. | volume = 49 | issue = 1 | pages = 223–241 | year = 2009 | pmid = 18834305 | pmc = 2676449 | doi = 10.1146/annurev.pharmtox.48.113006.094723 }}</ref> Reports also shown that the [[cancer cell]] under the Nutilin-3a treatment, acetylation of lys 382 was observed in the c-terminal of p53.<ref>{{cite journal | vauthors = Zajkowicz A, Krześniak M, Matuszczyk I, Głowala-Kosińska M, Butkiewicz D, Rusin M | title = Nutlin-3a, an MDM2 antagonist and p53 activator, helps to preserve the replicative potential of cancer cells treated with a genotoxic dose of resveratrol | journal = Mol. Biol. Rep. | volume = 40 | issue = 8 | pages = 5013–5026 | year = 2013 | pmid = 23666059 | pmc = 3723979 | doi = 10.1007/s11033-013-2602-7 }}</ref><ref>{{cite journal | vauthors = Kumamoto K, Spillare EA, Fujita K, Horikawa I, Yamashita T, Appella E, Nagashima M, Takenoshita S, Yokota J, Harris CC | title = Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence | journal = Cancer Res. | volume = 68 | issue = 9 | pages = 3193–3203 | year = 2008 | pmid = 18451145 | pmc = 2440635 | doi = 10.1158/0008-5472.CAN-07-2780 }}</ref>
-==== Microtubule ====
-[[File:Formation of Microtubule.png|thumb|400px|Formation of Microtubule]]
-The structure of [[microtubules]] is long, hollow cylinder dynamically assembled from α/β-[[tubulin]] dimers. They play an essential role in maintaining the structure of the cell as well as cell processes, for example, movement of [[organelles]].<ref>{{cite book| veditors = Kreis T, Vale R |title=Guidebook to the cytoskeletal and motor proteins|year=1999|publisher=Oxford Univ. Press|location=Oxford [u.a.] |isbn=0198599560 |edition=2nd }}</ref> In addition, [[microtubule]] is responsible of forming [[mitotic spindle]] in [[eukaryotic]] cells to transport [[chromosomes]] in [[cell division]].<ref>{{cite book| vauthors = Lodish H  |title=Molecular cell biology|year=2013|publisher=W.H. Freeman and Co.|location=New York|isbn=978-1429234139|edition=7th}}</ref><ref>{{cite book| veditors = Fojo T |title=The role of microtubules in cell biology, neurobiology, and oncology|year=2008|publisher=Humana Press|location=Totowa, N. J.|isbn=978-1588292940|edition=[Online-Ausg.]|url-access=registration|url=https://archive.org/details/microtubuletarge00anto}}</ref>
-===== Acetylation of tubulin =====
-[[File:Acetylation tubulin.png|thumb|400px|Acetylation tubulin]]
-The acetylated residue of α-[[tubulin]] is K40, which is catalyzed by α-tubulin acetyl-transferase (α-TAT) in human. The acetylation of K40 on α-tubulin is a hallmark of stable [[microtubules]]. The active site residues D157 and C120 of α-TAT1 are responsible for the catalysis because of the shape complementary to α-Tubulin. In addition, some unique structural features such as β4-β5 [[hairpin]], C-terminal loop, and α1-α2 loop regions are important for specific α-Tubulin [[molecular recognition]].<ref name="Friedmann 19655–19660">{{cite journal | vauthors = Friedmann DR, Aguilar A, Fan J, Nachury MV, Marmorstein R | title = Structure of the α-tubulin acetyltransferase, αTAT1, and implications for tubulin-specific acetylation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 109 | issue = 48 | pages = 19655–19660 | year = 2012 | pmid = 23071314 | doi = 10.1073/pnas.1209357109 | bibcode = 2012PNAS..10919655F | pmc=3511727| doi-access = free }}</ref> The reverse reaction of the acetylation is catalyzed by [[histone deacetylase]] 6.<ref>{{cite journal | vauthors = Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao TP | title = HDAC6 is a microtubule-associated deacetylase | journal = Nature | volume = 417 | issue = 6887 | pages = 455–458 | year = 2002 | pmid = 12024216 | doi = 10.1038/417455a | bibcode = 2002Natur.417..455H | s2cid = 4373254 }}</ref>
-===== Implications for cancer therapy =====
-Since [[microtubules]] play an important role in [[cell division]], especially in the [[G2 phase|G2/M phase]] of the [[cell cycle]], attempts have been made to impede [[microtubule]] function using small molecule inhibitors, which have been successfully used in clinics as cancer therapies.<ref>{{cite book|editor=Teresa Carlomagno |others=contributions by K.-H. Altmann|title=Tubulin-binding agents : synthetic, structural, and mechanistic insights|year=2009|publisher=Springer|location=Berlin|isbn=978-3540690368}}</ref> For example, the [[vinca]] alkaloids and [[taxanes]] selectively bind and inhibit [[microtubules]], leading to cell cycle arrest.<ref>{{cite book| veditors = Zito TL, Lemke TL, Williams DA, Roche VG, William S |title=Foye's principles of medicinal chemistry|year=2013|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-1609133450|edition=7th}}</ref> The identification of the crystal structure of acetylation of α-tubulin acetyl-transferase (α-TAT) also sheds a light on the discovery of small molecule that could modulate the stability or de-polymerization of [[tubulin]]. In other words, by targeting α-TAT, it is possible to prevent the tubulin from acetylation and result in the destabilization of tubulin, which is a similar mechanism for tubulin destabilizing agents.<ref name="Friedmann 19655–19660"/>
-==== STAT3 ====
-Signal transducer and activator of transcription 3 ([[STAT3]]) is a transcription factor that is phosphorylated by receptor associated [[kinases]], for example, [[Janus kinase|Janus-family tyrosine kinases]], and translocate to [[cell nucleus|nucleus]]. STAT3 regulates several genes in response to [[growth factors]] and [[cytokines]] and play an important role in cell growth. Therefore, [[STAT3]] facilitates [[oncogenesis]] in a variety of cell growth related pathways. On the other hand, it also play a role in the [[tumor suppressor]].<ref>{{cite book| vauthors = Müller-Decker FM, Klingmüller UK |title=Cellular signal processing : an introduction to the molecular mechanisms of signal transduction|year=2009|publisher=Garland Science|location=New York|isbn=978-0815342151}}</ref>
-===== Acetylation of STAT3 =====
-[[File:Structure and acetylation residue of STAT3.png|thumb|400px|Structure and acetylation residue of STAT3]]
-The acetylation of Lys685 of [[STAT3]] is important for [[STAT3]] homo-dimerization, which is essential for the DNA-binding and the transcriptional activation of [[oncogenes]]. The acetylation of [[STAT3]] is catalyzed by [[histone acetyltransferase]] [[p300-CBP coactivator family|p300]], and reversed by type 1 [[histone deacetylase]]. The lysine acetylation of STAT3 is also elevated in cancer cells.<ref>{{cite journal | vauthors = Yuan ZL, Guan YJ, Chatterjee D, Chin YE | title = Stat3 dimerization regulated by reversible acetylation of a single lysine residue | journal = Science | volume = 307 | issue = 5707 | pages = 269–273 | year = 2005 | pmid = 15653507 | doi = 10.1126/science.1105166 | bibcode = 2005Sci...307..269Y | s2cid = 25269192 }}</ref>
-===== Therapeutic implications for cancer therapy =====
-Since the acetylation of [[STAT3]] is important for its [[oncogenic]] activity and the fact that the level of acetylated STAT3 is high in cancer cells, it is implied that targeting acetylated STAT3 for [[chemoprevention]] and [[chemotherapy]] is a promising strategy. This strategy is supported by treating [[resveratrol]], an inhibitor of acetylation of STAT3, in cancer cell line reverses aberrant CpG island methylation.<ref>{{cite journal | vauthors = Lee H, Zhang P, Herrmann A, Yang C, Xin H, Wang Z, Hoon DS, Forman SJ, Jove R, Riggs AD, Yu H | title = Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 109 | issue = 20 | pages = 7765–7769 | year = 2012 | pmid = 22547799 | doi = 10.1073/pnas.1205132109 | bibcode = 2012PNAS..109.7765L | first3 = A. | pmc=3356652| doi-access = free }}</ref>
 == Acetylation of wood ==
@@ Line 187: / Line 19: @@
 *[[Acylation]]
 *[[Amide]]
-*[[Compendium of protein lysine acetylation]]
 *[[Ester]]
-*[[Glycosylation]]
-*[[Lipidation]]
-*[[Nitrosylation]]
 *[[Organic synthesis]]
-*[[Proteolysis]]
 == References ==
 {{Reflist|35em}}
-{{Protein posttranslational modification}}
 [[Category:Organic reactions]]
-[[Category:Post-translational modification]]

Revision as of 04:02, 25 September 2021

Acetylation of wood

See also

References