Acetylation refers to the process of introducing an acetyl group (resulting in an acetoxy group) into a compound, namely the substitution of an acetyl group for an active hydrogen atom. A reaction involving the replacement of the hydrogen atom of a hydroxyl group with an acetyl group (CH3 CO) yields a specific ester, the acetate. Acetic anhydride is commonly used as an acetylating agent reacting with free hydroxyl groups. For example, it is used in the synthesis of aspirin and heroin.
- 1 Acetylation of Proteins
- 1.1 N-terminal Acetylation, an Important Example of Co-translational Acetylation on Proteins
- 1.1.1 General Introduction of N-terminal Acetylation
- 1.1.2 N-terminal Acetyltransferases
- 1.1.3 Function of N-terminal Acetylation
- 1.1.4 N-terminal Acetylation in Cancer
- 1.2 Lysine acetylation and deacetylation
- 1.3 Important examples of lysine acetylation in proteins
- 1.3.1 p53
- 1.3.2 Microtubule
- 1.3.3 STAT3
- 1.1 N-terminal Acetylation, an Important Example of Co-translational Acetylation on Proteins
- 2 Acetylation of wood
- 3 See also
- 4 References
Acetylation of Proteins
Acetylation is an important modification of proteins in cell biology; and proteomics studies have identified thousands of acetylated mammalian proteins. Protein modification consists of co-translational modification and post-translational modification. Co-translational modification is the process of covalently altering one or more amino acids in a protein at the same time as its mRNA is being translated on polyribosomes; and post-translational modification includes protein phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation, lipidation and proteolysis before becoming the mature protein product. Acetylation occurs as a co-translational and post-translational modification of proteins, for example, histones, p53, and tubulins. 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 enteric are acetylated.
N-terminal Acetylation, an Important Example of Co-translational Acetylation on Proteins
General Introduction of N-terminal Acetylation
N-terminal acetylation is one of the most common co-translational covalent modifications of proteins in eukaryotes and it’s crucial for the regulation and function of different proteins. N-terminal acetylation plays an important role in the synthesis, stability and localization of proteins. And about 85% of all human proteins and 68% in yeast are acetylated at their Nα-terminus. Several proteins from prokaryotes and archaebacteria are also modified by N-terminal acetylation.
N-terminal Acetylation is catalyzed by a set of enzyme complexes, the N-terminal acetyltransferases (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-termini, and the acetylation was found to be irreversible so far.
In total, there are six different NATs have been reported in humans, they are NatA, NatB, NatC, NatD, NatE and NatF. Each of these different enzyme complexes is specific for different amino acids or amino acid sequences which is show in the following table.
Table 1. The Composition and Substrate specificity of NATs
|NatA||Naa10p (Ard1p) Naa5p (Nat1p)||Ser-, Ala-, Gly-, Thr-, Val-, Cys- N-termini|
|NatB||Naa20p (Nat3p) Naa25p (Mdm20p)||Met-Glu-, Met-Asp-, Met-Asn-, Met-Gln- N-termini|
|NatC||Naa30p (Mak3p) Naa35p (Mak10p) Naa40p (Nat5p)||Met-Leu-, Met-Ile-, Met-Trp-, Met-Phe- N-termini|
|NatD||Naa40p (Nat4p)||Ser-Gly-Gly-, Ser-Gly-Arg- N-termini|
|NatE||Naa10p (Ard1p) Naa5p (Nat1p) Naa50p (Nat5p)||Met-Leu-, Met-Ala-, Met-Lys-, Met-Met- N-termini|
|NatF||Naa60p||Met-Lys-, Met-Leu-, Met-Ile-, Met-Trp-, Met-Phe- N-termini|
NatA is composed of two subunits, the catalytic subunit Naa10p and the auxiliary subunit Naa15p. It was found that NatA subunits are more complex in higher eukaryotes than in lower eukaryotes. Both of the gene hNAA10, hNAA15, which is from human and the orthologous NAA11 and NAA16, which is from bacterial, could make functional gene products, which might form different active hNatA complexes. At least four possible hNatA complexes are formed with the hNaa10p-hNaa15p dimer, which makes NatA to be considered to the most abundant Nat.
NatA acetylates Ser, Ala-, Gly-, Thr-, Val- and 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.
Several different interaction partners are involved in the N-terminal acetylation by NatA. Huntingtin interacting protein K (HYPK) interacts with hNatA on ribosome to affect the N-terminal acetylation of a subset of NatA substrates. Subunits hNaa10p and hNaa15p will increase the tendency for aggregation of Huntingtin if HYPK is depleted. Hypoxia-inducible factor (HIF)-1α has also been found to interact with hNaa10p to inhibit hNaa10p-mediated activation of β-catenin transcriptional activity.
NatB complexes are composed with 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 Met-Glu-, Met-Asp-, Met-Asn- or Met-Gln- N termini.
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 Met-Leu-, Met-Ile-, Met-Trp- or Met-Phe N-termini.
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-acetyltransferases (KATs).
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.
NatF is a newly identified NAT in 2011, which is composed with Naa60p enzyme. Till now, NatF is only found in higher eukaryotes, but not in lower eukaryotes. Compared to yeast, NatF contributes to the higher abundance of N-terminal acetylation in humans. NatF complex acetylates the N-terminal methionine of substrates Met-Lys-, Met-Leu-, Met-Ile-, Met-Trp- and Met-Phe N termini which are partly overlapping with NatC and NatE.
Function of N-terminal Acetylation
N-terminal acetylation of proteins can affect protein stability but the results and mechanism is not very clear till now. 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. But several studies have shown that the N-terminal acetylated protein have a similar degradation rate as proteins with a non-blocked N-terminus.
N-terminal acetylation affects protein localization
N-terminal acetylation has been shown that it can steer the localization of proteins. Arl3p contains a Phe (Yeast Arl3p), Tyr (Human Arl3p) which could be acetylated by NatC. Arl3p is one of the ‘Arf-like’ (Arl) GTPases, which is crucial for the organization of member traffic. It requires its Nα-acetyl group for its targeting to the Golgi membrane by the interaction with Golgi membrane-residing protein Sys1p. If the Phe or Tyr is replaced by an 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.
N-terminal acetylation affects 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. 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.
N-terminal acetylation affects 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.
N-terminal Acetylation in 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 carcinoma. 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
|Nat subunits||Cancer tissue||Expression pattern|
|hNaa10p||lung cancer, breast cancer, colorectal cancer, hepatocellular carcinoma||high in tumors|
|hNaa10p||lung cancer, breast cancer, pancreatic cancer, ovarian cancer||loss of heterozygosity in tumors|
|hNaa10p||breast cancer, gastric cancer, lung cancer||high in primary tumors, but low with lymph node metastases|
|hNaa10p||Non-small cell lung cancer||low in tumors|
|hNaa15p||papillary thyroid carcinoma, gastric cancer||high in tumors|
|hNaa15p||neuroblastoma||high in advanced stage tumors|
|hNaa11p||hepatocellular carcinoma||loss of heterozygosity in tumors|
Lysine acetylation and deacetylation
Proteins are typically acetylated on lysine residues and this reaction relies on 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 enzymes with histone acetyltransferase (HAT) or histone deacetylase (HDAC) activity, although HATs and HDACs can modify the acetylation status of non-histone proteins as well.
The regulation of transcription factors, effector proteins, molecular chaperones, and cytoskeletal proteins by acetylation and deacetylation is a significant post-translational regulatory mechanism These regulatory mechanisms are analogous to phosphorylation and dephosphorylation by the action of 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. The regulation of tubulin protein is an example of this in mouse neurons and astroglia. 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.
The discovery of histone acetylation (and deacetylation) has been proved to be important in the transcriptional regulation in the field of epigenetic. However, histone is not the only protein that is highly regulated by posttranslational acetylation. In the following examples, we choose the following proteins that are important in biology that regulate the important signal transduction in biology by acetylation of proteins. In addition, the acetylation regulation on those proteins also related to human diseases and has a potential for the development for therapy.
Important examples of lysine acetylation in proteins
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." In addition, 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.
Acetylation of p53
The acetylation of p53 is indispensable for its activation. It has been reported that the acetylation level of p53 will increase significantly when cell undergo stress. There are three major acetylation site on p53: K164, K120 and C terminus. If only one of the acetylation sites is defected, the activation of p21 is still observed. However, if all three activation sites are blocked, the activation of p21 and the suppression of cell growth caused by p53 will be completely lost. In addition, the acetylation of p53 prevent its binding from the repressor Mdm2 on DNA. In addition, it is also suggested that the p53 acetylation is crucial for its transcription-independent proapoptotic functions.
Therapeutic 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 is a small molecule designed to target p53 and Mdm2 interaction that kept p53 from deactivation. Reports also shown that the cancer cell under the Nutilin-3a treatment, acetylation of lys 382 was observed in the c-terminal of p53.
The structure of microtubules is long, hollow cylinder dynamically assembled from α/β-tubulin dimers. They are play an essential role in maintaining the structure of the cell as well as cell processes, for example, movement of organelles. In addition, microtubule is responsible of forming mitotic spindle in eukaryotic cells to transport chromosomes in cell division.
Acetylation of 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. The reverse reaction of the acetylation is catalyzed by histone deacetylase 6.
Therapeutic implications for cancer therapy
Since the microtubules play an important role in the cell division especially in the G2/M phase of the cell cycle, attempts has been made to modulate the microtubule by binding the to tubulin and were successfully used in clinics. For example, vinca alkaloids and taxanes will destabilize and stabilize tubulin respective and result in the anomaly of cell division. 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.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is phosphorylated by receptor associated kinases, for example, Janus-family tyrosine kinases, and translocate to 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.
Acetylation 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, and reversed by type 1 histone deacetylase. The lysine acetylation of STAT3 is also elevated in cancer cells.
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.
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. Accoya wood is a commercial, patented acetylated wood.
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.
- Choudhary, C.; Kumar, C.; Gnad, F.; Nielsen, M. L.; Rehman, M.; Walther, T. C.; Olsen, J. V.; Mann, M. (16 July 2009). "Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions". Science 325 (5942): 834–840. Bibcode:2009Sci...325..834C. doi:10.1126/science.1175371. PMID 19608861.
- Fritz, Kristofer S.; Galligan, James J.; Hirschey, Matthew D.; Verdin, Eric; Petersen, Dennis R. (2 March 2012). "Mitochondrial Acetylome Analysis in a Mouse Model of Alcohol-Induced Liver Injury Utilizing SIRT3 Knockout Mice". Journal of Proteome Research 11 (3): 1633–1643. doi:10.1021/pr2008384. PMC 3324946. PMID 22309199.
- Brook, Tom. "Protein Acetylation: Much More than Histone Acetylation". Cayman Chemical.
- Heal, William P.; Wickramasinghe, Sasala R.; Bowyer, Paul W.; Holder, Anthony A.; Smith, Deborah F.; Leatherbarrow, Robin J.; Tate, Edward W. (2008). "Site-specific N-terminal labelling of proteins in vitro and in vivo using N-myristoyl transferase and bioorthogonal ligation chemistry". Chemical Communications (4): 480. doi:10.1039/b716115h.
- Robert K. Murray ... (2003). Harper's illustrated biochemistry (26th ed.). New York ; London: McGraw-Hill. ISBN 0-07-138901-6.
- 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, S. M.; He, F.; Qin, L.; Chin, J.; Yang, P.; Chen, X.; Lei, Q.; Xiong, Y.; Guan, K.-L.; Jiang, Wenqing; Yu, Wei; Lin, Yan; Zhang, Tengfei; Yao, Jun; Zhou, Li; Zeng, Yaxue; Li, Hong; Li, Yixue; Shi, Jiong; An, Wenlin; Hancock, Susan M.; He, Fuchu; Qin, Lunxiu; Chin, Jason; Yang, Pengyuan; Chen, Xian; Lei, Qunying; Xiong, Yue; Guan, Kun-Liang (18 February 2010). "Regulation of Cellular Metabolism by Protein Lysine Acetylation". Science 327 (5968): 1000–1004. Bibcode:2010Sci...327.1000Z. doi:10.1126/science.1179689. PMC 3232675. PMID 20167786.
- Van Damme, Petra; Hole, Kristine; Pimenta-Marques, Ana; Helsens, Kenny; Vandekerckhove, Joël; Martinho, Rui G.; Gevaert, Kris; Arnesen, Thomas; Snyder, Michael (7 July 2011). "NatF Contributes to an Evolutionary Shift in Protein N-Terminal Acetylation and Is Important for Normal Chromosome Segregation". PLoS Genetics 7 (7): e1002169. doi:10.1371/journal.pgen.1002169. PMC 3131286. PMID 21750686.
- Starheim, Kristian K.; Gevaert, Kris; Arnesen, Thomas (April 2012). "Protein N-terminal acetyltransferases: when the start matters". Trends in Biochemical Sciences 37 (4): 152–161. doi:10.1016/j.tibs.2012.02.003. PMID 22405572.
- Starheim, Kristian K; Gromyko, Darina; Velde, Rolf; Varhaug, Jan; Arnesen, Thomas (2009). "Composition and biological significance of the human Nα-terminal acetyltransferases". BMC Proceedings 3 (Suppl 6): S3. doi:10.1186/1753-6561-3-s6-s3. PMC 2722096. PMID 19660096.
- Arnesen, T.; Van Damme, P.; Polevoda, B.; Helsens, K.; Evjenth, R.; Colaert, N.; Varhaug, J. E.; Vandekerckhove, J.; Lillehaug, J. R.; Sherman, F.; Gevaert, K.; Polevoda, Bogdan; Helsens, Kenny; Evjenth, Rune; Colaert, Niklaas; Varhaug, Jan Erik; Vandekerckhove, Joël; Lillehaug, Johan R.; Sherman, Fred; Gevaert, Kris (6 May 2009). "Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans". Proceedings of the National Academy of Sciences 106 (20): 8157–8162. Bibcode:2009PNAS..106.8157A. doi:10.1073/pnas.0901931106.
- Arnesen, T.; Starheim, K. K.; Van Damme, P.; Evjenth, R.; Dinh, H.; Betts, M. J.; Ryningen, A.; Vandekerckhove, J.; Gevaert, K.; Anderson, D. (12 February 2010). "The Chaperone-Like Protein HYPK Acts Together with NatA in Cotranslational N-Terminal Acetylation and Prevention of Huntingtin Aggregation". Molecular and Cellular Biology 30 (8): 1898–1909. doi:10.1128/mcb.01199-09. PMC 2849469. PMID 20154145.
- Liszczak, Glen; Goldberg, Jacob M; Foyn, Håvard; Petersson, E James; Arnesen, Thomas; Marmorstein, Ronen (4 August 2013). "Molecular basis for N-terminal acetylation by the heterodimeric NatA complex". Nature Structural & Molecular Biology 20 (9): 1098–1105. doi:10.1038/nsmb.2636.
- Hole, Kristine; Van Damme, Petra; Dalva, Monica; Aksnes, Henriette; Glomnes, Nina; Varhaug, Jan Erik; Lillehaug, Johan R.; Gevaert, Kris; Arnesen, Thomas; Imhof, Axel (15 September 2011). "The Human N-Alpha-Acetyltransferase 40 (hNaa40p/hNatD) Is Conserved from Yeast and N-Terminally Acetylates Histones H2A and H4". PLoS ONE 6 (9): e24713. Bibcode:2011PLoSO...624713H. doi:10.1371/journal.pone.0024713. PMC 3174195. PMID 21935442.
- Gautschi, M.; Just, S.; Mun, A.; Ross, S.; Rucknagel, P.; Dubaquie, Y.; Ehrenhofer-Murray, A.; Rospert, S. (29 September 2003). "The Yeast N -Acetyltransferase NatA Is Quantitatively Anchored to the Ribosome and Interacts with Nascent Polypeptides". Molecular and Cellular Biology 23 (20): 7403–7414. doi:10.1128/mcb.23.20.7403-7414.2003. PMC 230319. PMID 14517307.
- Hollebeke, Jolien; Van Damme, Petra; Gevaert, Kris (1 January 2012). "N-terminal acetylation and other functions of Nα-acetyltransferases". Biological Chemistry 393 (4).
- Hershko, A.; Heller, H.; Eytan, E.; Kaklij, G.; Rose, I. A. (1 November 1984). "Role of the alpha-amino group of protein in ubiquitin-mediated protein breakdown". Proceedings of the National Academy of Sciences 81 (22): 7021–7025. Bibcode:1984PNAS...81.7021H. doi:10.1073/pnas.81.22.7021.
- Hwang, C.-S.; Shemorry, A.; Varshavsky, A. (28 January 2010). "N-Terminal Acetylation of Cellular Proteins Creates Specific Degradation Signals". Science 327 (5968): 973–977. Bibcode:2010Sci...327..973H. doi:10.1126/science.1183147. PMID 20110468.
- Behnia, Rudy; Panic, Bojana; Whyte, James R. C.; Munro, Sean (11 April 2004). "Targeting of the Arf-like GTPase Arl3p to the Golgi requires N-terminal acetylation and the membrane protein Sys1p". Nature Cell Biology 6 (5): 405–413. doi:10.1038/ncb1120. PMID 15077113.
- Starheim, K. K.; Gromyko, D.; Evjenth, R.; Ryningen, A.; Varhaug, J. E.; Lillehaug, J. R.; Arnesen, T. (27 April 2009). "Knockdown of Human N -Terminal Acetyltransferase Complex C Leads to p53-Dependent Apoptosis and Aberrant Human Arl8b Localization". Molecular and Cellular Biology 29 (13): 3569–3581. doi:10.1128/mcb.01909-08. PMC 2698767. PMID 19398576.
- Gromyko, Darina; Arnesen, Thomas; Ryningen, Anita; Varhaug, Jan Erik; Lillehaug, Johan R. (15 December 2010). "Depletion of the human Nα-terminal acetyltransferase A induces p53-dependent apoptosis and p53-independent growth inhibition". International Journal of Cancer 127 (12): 2777–2789. doi:10.1002/ijc.25275.
- Yi, Caroline H.; Pan, Heling; Seebacher, Jan; Jang, Il-Ho; Hyberts, Sven G.; Heffron, Gregory J.; Vander Heiden, Matthew G.; Yang, Renliang; Li, Fupeng; Locasale, Jason W.; Sharfi, Hadar; Zhai, Bo; Rodriguez-Mias, Ricard; Luithardt, Harry; Cantley, Lewis C.; Daley, George Q.; Asara, John M.; Gygi, Steven P.; Wagner, Gerhard; Liu, Chuan-Fa; Yuan, Junying (August 2011). "Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival". Cell 146 (4): 607–620. doi:10.1016/j.cell.2011.06.050. PMC 3182480. PMID 21854985.
- Kamita, Masahiro; Kimura, Yayoi; Ino, Yoko; Kamp, Roza M.; Polevoda, Bogdan; Sherman, Fred; Hirano, Hisashi (April 2011). "Nα-Acetylation of yeast ribosomal proteins and its effect on protein synthesis". Journal of Proteomics 74 (4): 431–441. doi:10.1016/j.jprot.2010.12.007. PMID 21184851.
- Tan (16 March 2009). "Immunohistochemical analysis of human arrest-defective-1 expressed in cancers in vivo". Oncology Reports 21 (4). doi:10.3892/or_00000303.
- Kalvik, T V; Arnesen, T (5 March 2012). "Protein N-terminal acetyltransferases in cancer". Oncogene 32 (3): 269–276. doi:10.1038/onc.2012.82. PMID 22391571.
- Sadoul K, Boyault C, Pabion M, Khochbin S; Boyault; Pabion; Khochbin (February 2008). "Regulation of protein turnover by acetyltransferases and deacetylases". Biochimie 90 (2): 306–12. doi:10.1016/j.biochi.2007.06.009. PMID 17681659.
- Glozak MA, Sengupta N, Zhang X, Seto E; Sengupta; Zhang; Seto (2005). "Acetylation and deacetylation of non-histone proteins". Gene 363: 15–23. doi:10.1016/j.gene.2005.09.010. PMID 16289629.
- Yang XJ, Seto E; Seto (2008). "Lysine acetylation: codified crosstalk with other posttranslational modifications". Mol Cell 31 (4): 449–61. doi:10.1016/j.molcel.2008.07.002. PMC 2551738. PMID 18722172.
- Eddé, Bernard; et al.; De Néchaud, B; Koulakoff, A; Berwald-Netter, Y; Gros, F (1989). "Posttranslational modifications of tubulin in cultured mouse brain neurons and astroglia". Biology of the Cell 65 (2): 109–117. doi:10.1016/0248-4900(89)90018-x. PMID 2736326.
- Maruta, H; et al. (1 August 1986). "The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules". JBC 103 (2): 571–579. doi:10.1083/jcb.103.2.571. PMC 2113826. PMID 3733880.
- Alberts, Bruce (March 2002). Molecular Biology of the Cell. Garland Science. ISBN 0815332181.
- Weinberg, Robert A. (2013). Biology of cancer. (2. ed.). [S.l.]: Garland Science. ISBN 0815342209.
- Brooks, Christopher L.; Gu, Wei (12 July 2011). "The impact of acetylation and deacetylation on the p53 pathway". Protein & Cell 2 (6): 456–462. doi:10.1007/s13238-011-1063-9.
- Tang, Yi; Zhao, Wenhui; Chen, Yue; Zhao, Yingming; Gu, Wei (May 2008). "Acetylation Is Indispensable for p53 Activation". Cell 133 (4): 612–626. doi:10.1016/j.cell.2008.03.025. PMC 2914560. PMID 18485870.
- Yamaguchi, H.; Woods, N. T.; Piluso, L. G.; Lee, H.-H.; Chen, J.; Bhalla, K. N.; Monteiro, A.; Liu, X.; Hung, M.-C.; Wang, H.-G. (5 March 2009). "p53 Acetylation Is Crucial for Its Transcription-independent Proapoptotic Functions". Journal of Biological Chemistry 284 (17): 11171–11183. doi:10.1074/jbc.M809268200. PMC 2670122. PMID 19265193.
- Vassilev, L. T.; Vu, Binh T.; Graves, Bradford; Carvajal, Daisy; Podlaski, Frank; Filipovic, Zoran; Kong, Norman; Kammlott, Ursula; Lukacs, Christine; Klein, Christian; Fotouhi, Nader; Liu, Emily A. (6 February 2004). "In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2". Science 303 (5659): 844–848. Bibcode:2004Sci...303..844V. doi:10.1126/science.1092472. PMID 14704432.
- Shangary, Sanjeev; Wang, Shaomeng (February 2009). "Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction to Reactivate p53 Function: A Novel Approach for Cancer Therapy". Annual Review of Pharmacology and Toxicology 49 (1): 223–241. doi:10.1146/annurev.pharmtox.48.113006.094723. PMC 2676449. PMID 18834305.
- Zajkowicz, Artur; Krześniak, Małgorzata; Matuszczyk, Iwona; Głowala-Kosińska, Magdalena; Butkiewicz, Dorota; Rusin, Marek (11 May 2013). "Nutlin-3a, an MDM2 antagonist and p53 activator, helps to preserve the replicative potential of cancer cells treated with a genotoxic dose of resveratrol". Molecular Biology Reports 40 (8): 5013–5026. doi:10.1007/s11033-013-2602-7. PMC 3723979. PMID 23666059.
- Kumamoto, K.; Spillare, E. A.; Fujita, K.; Horikawa, I.; Yamashita, T.; Appella, E.; Nagashima, M.; Takenoshita, S.; Yokota, J.; Harris, C. C. (1 May 2008). "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". Cancer Research 68 (9): 3193–3203. doi:10.1158/0008-5472.CAN-07-2780. PMC 2440635. PMID 18451145.
- Kreis, ed. by Thomas; Vale, Ronald (1999). Guidebook to the cytoskeletal and motor proteins (2. ed.). Oxford [u.a.]: Oxford Univ. Press. ISBN 0198599560.
- al.], Harvey Lodish ... [et (2013). Molecular cell biology (7th ed.). New York: W.H. Freeman and Co. ISBN 142923413X.
- Fojo, edited by Tito (2008). The role of microtubules in cell biology, neurobiology, and oncology ([Online-Ausg.] ed.). Totowa, N. J.: Humana Press. ISBN 1588292940.
- Friedmann, D. R.; Aguilar, A.; Fan, J.; Nachury, M. V.; Marmorstein, R. (15 October 2012). "Structure of the -tubulin acetyltransferase, TAT1, and implications for tubulin-specific acetylation". Proceedings of the National Academy of Sciences 109 (48): 19655–19660. Bibcode:2012PNAS..10919655F. doi:10.1073/pnas.1209357109.
- Hubbert, Charlotte; Guardiola, Amaris; Shao, Rong; Kawaguchi, Yoshiharu; Ito, Akihiro; Nixon, Andrew; Yoshida, Minoru; Wang, Xiao-Fan; Yao, Tso-Pang (23 May 2002). "HDAC6 is a microtubule-associated deacetylase". Nature 417 (6887): 455–458. Bibcode:2002Natur.417..455H. doi:10.1038/417455a. PMID 12024216.
- Tubulin-binding agents : synthetic, structural, and mechanistic insights. Berlin: Springer. 2009. ISBN 3540690360.
|last1=in Authors list (help)
- Zito, edited by Thomas L. Lemke, David A. Williams ; associate editors, Victoria F. Roche, S. William (2013). Foye's principles of medicinal chemistry (7th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 1609133455.
- Müller-Decker, Friedrich Marks, Ursula Klingmüller, Karin (2009). Cellular signal processing : an introduction to the molecular mechanisms of signal transduction. New York: Garland Science. ISBN 0815342152.
- Yuan, Z.-l.; Guan, Ying-jie; Chatterjee, Devasis; Chin, Y. Eugene (14 January 2005). "Stat3 Dimerization Regulated by Reversible Acetylation of a Single Lysine Residue". Science 307 (5707): 269–273. Bibcode:2005Sci...307..269Y. doi:10.1126/science.1105166. PMID 15653507.
- Lee, H.; Zhang, P.; Herrmann, A.; Yang, C.; Xin, H.; Wang, Z.; Hoon, D. S. B.; Forman, S. J.; Jove, R.; Riggs, A. D.; Yu, H.; Herrmann, A.; Yang, C.; Xin, H.; Wang, Z.; Hoon, D. S. B.; Forman, S. J.; Jove, R.; Riggs, A. D.; Yu, H. (30 April 2012). "Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation". Proceedings of the National Academy of Sciences 109 (20): 7765–7769. Bibcode:2012PNAS..109.7765L. doi:10.1073/pnas.1205132109.