Post-translational modifications of Drosophila melanogaster HOX protein, Sex combs reduced

Autoři: Anirban Banerjee aff001;  Anthony Percival-Smith aff001
Působiště autorů: Department of Biology, The University of Western Ontario, London, Ontario, Canada aff001
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article


Homeotic selector (HOX) transcription factors (TFs) regulate gene expression that determines the identity of Drosophila segments along the anterior-posterior (A-P) axis. The current challenge with HOX proteins is understanding how they achieve their functional specificity while sharing a highly conserved homeodomain (HD) that recognize the same DNA binding sites. One mechanism proposed to regulate HOX activity is differential post-translational modification (PTM). As a first step in investigating this hypothesis, the sites of PTM on a Sex combs reduced protein fused to a triple tag (SCRTT) extracted from developing embryos were identified by Tandem Mass Spectrometry (MS/MS). The PTMs identified include phosphorylation at S185, S201, T315, S316, T317 and T324, acetylation at K218, S223, S227, K309, K434 and K439, formylation at K218, K309, K325, K341, K369, K434 and K439, methylation at S19, S166, K168 and T364, carboxylation at D108, K298, W307, K309, E323, K325 and K369, and hydroxylation at P22, Y87, P107, D108, D111, P269, P306, R310, N321, K325, Y334, R366, P392 and Y398. Of the 44 modifications, 18 map to functionally important regions of SCR. Besides a highly conserved DNA-binding HD, HOX proteins also have functionally important, evolutionarily conserved small motifs, which may be Short Linear Motifs (SLiMs). SLiMs are proposed to be preferential sites of phosphorylation. Although 6 of 7 phosphosites map to regions of predicted SLiMs, we find no support for the hypothesis that the individual S, T and Y residues of predicted SLiMs are phosphorylated more frequently than S, T and Y residues outside of predicted SLiMs.

Klíčová slova:

Amino acid analysis – Drosophila melanogaster – Homeobox – Lysine – Phosphorylation – Sequence motif analysis – Hydroxylation – Formylation


1. Akam M. Hox genes, homeosis and the evolution of segmental identity: no need for hopeless monsters. Int J Dev Biol. 1998;42: 445–451. doi: 10.1387/ijdb.9654030 9654030

2. Lewis EB. A gene complex controlling segmentation in Drosophila. Nature. 1978;276: 565–570. doi: 10.1038/276565a0 103000

3. Gehring WJ, Qian YQ, Billeter M, Furukubo-Tokunaga K, Schier AF, Resendez-Perez D, et al. Homeodomain-DNA recognition. Cell. 1994;78: 211–223. doi: 10.1016/0092-8674(94)90292-5 8044836

4. Primon M, Hunter KD, Pandha HS, Morgan R. Kinase Regulation of HOX Transcription Factors. Cancers. 2019;11: E508. doi: 10.3390/cancers11040508 30974835

5. Draime A, Bridoux L, Graba Y, Rezsohazy R. Post-translational modifications of HOX proteins, an underestimated issue. Int J Dev Biol. 2018;62: 733–744. doi: 10.1387/ijdb.180178rr 30604843

6. Sivanantharajah L, Percival-Smith A. Differential pleiotropy and HOX functional organization. Dev Biol. 2015;398: 1–10. doi: 10.1016/j.ydbio.2014.11.001 25448696

7. Lewis RA, Wakimoto BT, Denell RE, Kaufman TC. Genetic analysis of the Antennapedia gene complex (ANT-C) and adjacent chromosomal regions of Drosophila melanogaster. II. Polytene chromosome segments 84A-84B1,2. Genetics. 1980;95: 383–397. 17249042

8. Struhl G. Genes controlling segmental specification in the Drosophila thorax. Proc Natl Acad Sci U S A. 1982;79: 7380–7384. doi: 10.1073/pnas.79.23.7380 6961417

9. Panzer S, Weigel D, Beckendorf SK. Organogenesis in Drosophila melanogaster: embryonic salivary gland determination is controlled by homeotic and dorsoventral patterning genes. Development. 1992;114: 49–57. 1349523

10. Percival-Smith A, Weber J, Gilfoyle E, Wilson P. Genetic characterization of the role of the two HOX proteins, Proboscipedia and Sex Combs Reduced, in determination of adult antennal, tarsal, maxillary palp and proboscis identities in Drosophila melanogsater. Development. 1997;124: 5049–5062. 9362475

11. Percival-Smith A, Sivanantharajah L, Pelling JJH, Teft WA. Developmental competence and the induction of ectopic proboscises in Drosophila melanogaster. Dev Genes Evol. 2013;223: 375–387. doi: 10.1007/s00427-013-0454-8 24121940

12. Ryoo HD, Mann RS. The control of trunk Hox specificity and activity by Extradenticle. Genes Dev. 1999;13: 1704–1716. doi: 10.1101/gad.13.13.1704 10398683

13. Tour E, Hittinger CT, McGinnis W. Evolutionarily conserved domains required for activation and repression functions of the Drosophila Hox protein Ultrabithorax. Development. 2005; 132: 5271–5281. doi: 10.1242/dev.02138 16284118

14. Sivanantharajah L, Percival-Smith A. Analysis of the sequence and phenotype of Drosophila Sex combs reduced alleles reveals potential functions of conserved protein motifs of the Sex combs reduced protein. Genetics. 2009;182: 191–203. doi: 10.1534/genetics.109.100438 19293143

15. Sivanantharajah L, Percival-Smith A. Acquisition of a leucine zipper motif as a mechanism of antimorphy for an allele of the Drosophila Hox gene Sex combs reduced. G3-Genes Genom Genet. 2014;4: 829–838. doi: 10.1534/g3.114.010769

16. Joshi R, Passner JM, Rohs R, Jain R, Sosinsky A, Crickmore MA, et al. Functional Specificity of a Hox Protein Mediated by the Recognition of Minor Groove Structure. Cell. 2007;131: 530–543. doi: 10.1016/j.cell.2007.09.024 17981120

17. Hittinger CT, Stern DL, Carroll SB. Pleiotropic functions of a conserved insect-specific Hox peptide motif. Development. 2005;132: 5261–5270. doi: 10.1242/dev.02146 16267091

18. Prince F, Katsuyama T, Oshima Y, Plaza S, Resendez-Perez D, Berry M, et al. The YPWM motif links Antennapedia to the basal transcriptional machinery. Development. 2008;135: 1669–1679. doi: 10.1242/dev.018028 18367556

19. Merabet S, Litim-Mecheri I, Karlsson D, Dixit R, Saadaoui M, Monier B, et al. Insights into Hox protein function from a large scale combinatorial analysis of protein domains. PLoS Genet. 2011;7: e1002302. doi: 10.1371/journal.pgen.1002302 22046139

20. Neduva V, Linding R, Su-Angrand I, Stark A, de Masi F, Gibson TJ, et al. Systematic discovery of new recognition peptides mediating protein interaction networks. PLoS Biol. 2005;3: e405. doi: 10.1371/journal.pbio.0030405 16279839

21. Neduva V, Russell RB. Peptides mediating interaction networks: new leads at last. Curr Opin Biotechnol. 2006;17: 465–471. doi: 10.1016/j.copbio.2006.08.002 16962311

22. Davey NE, Van Roey K, Weatheritt RJ, Toedt G, Uyar B, Altenberg B, et al. Attributes of short linear motifs. Mol BioSyst. 2012;8: 268–281. doi: 10.1039/c1mb05231d 21909575

23. Van Roey K, Uyar B, Weatheritt RJ, Dinkel H, Seiler M, Budd A, et al. Short linear motifs: ubiquitous and functionally diverse protein interaction modules directing cell regulation. Chem Rev. 2014;114: 6733–6778. doi: 10.1021/cr400585q 24926813

24. Puntervoll P, Linding R, Gemünd C, Chabanis-Davidson S, Mattingsdal M, Cameron S, et al. ELM server: a new resource for investigating short functional sites in modular eukaryotic proteins. Nucleic Acids Res. 2003;31: 3625–3630. doi: 10.1093/nar/gkg545 12824381

25. Iakoucheva LM, Radivojac P, Brown CJ, O’Connor TR, Sikes JG, Obradovic Z, et al. The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Res. 2004;32: 1037–1049. doi: 10.1093/nar/gkh253 14960716

26. Khan AN, Lewis PN. Unstructured conformations are a substrate requirement for the Sir2 family of NAD-dependent protein deacetylases. J Biol Chem. 2005;280: 36073–36078. doi: 10.1074/jbc.M508247200 16131486

27. Gould CM, Diella F, Via A, Puntervoll P, Gemünd C, Chabanis-Davidson S, et al. ELM: the status of the 2010 eukaryotic linear motif resource. Nucleic Acids Res. 2010; 38: D167–D180. doi: 10.1093/nar/gkp1016 19920119

28. Gouw M, Michael S, Sámano-Sánchez H, Kumar M, Zeke A, Lang B, et al. The eukaryotic linear motif resource—2018 update. Nucleic Acids Res. 2018;46: D428–D434. doi: 10.1093/nar/gkx1077 29136216

29. Uyar B, Weatheritt RJ, Dinkel H, Davey NE, Gibson TJ. Proteome-wide analysis of human disease mutations in short linear motifs: neglected players in cancer? Mol Biosyst. 2014;10: 2626–2642. doi: 10.1039/c4mb00290c 25057855

30. Hraber P, O’Maille PE, Silberfarb A, Davis-Anderson K, Generous N, McMahon BH, et al. Resources to Discover and Use Short Linear Motifs in Viral Proteins. Trends Biotechnol. 2019; Article in press. doi: 10.1016/j.tibtech.2019.07.004

31. Davey NE, Travé G, Gibson TJ. How viruses hijack cell regulation. Trends Biochem Sci. 2011;36: 159–169. doi: 10.1016/j.tibs.2010.10.002 21146412

32. Gógl G, Biri-Kovács B, Durbesson F, Jane P, Nomine Y, Kostmann C, et al. Rewiring of RSK-PDZ Interactome by Linear Motif Phosphorylation. J Mol Biol. 2019;431: 1234–1249. doi: 10.1016/j.jmb.2019.01.038 30726710

33. Mylin LM, Bhat JP, Hopper JE. Regulated phosphorylation and dephosphorylation of GAL4, a transcriptional activator. Genes Dev. 1989;3: 1157–1165. doi: 10.1101/gad.3.8.1157 2676720

34. Hunter T, Karin M. The regulation of transcription by phosphorylation. Cell. 1992;70: 375–387. doi: 10.1016/0092-8674(92)90162-6 1643656

35. Ardito F, Giuliani M, Perrone D, Troiano G, Lo Muzio L. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review). Int J Mol Med. 2017;40: 271–280. doi: 10.3892/ijmm.2017.3036 28656226

36. Berry M, Gehring W. Phosphorylation status of the SCR homeodomain determines its functional activity: essential role for protein phosphatase 2A,B’. EMBO J. 2000;19: 2946–2957. doi: 10.1093/emboj/19.12.2946 10856239

37. Jaffe L, Ryoo HD, Mann RS. A role for phosphorylation by casein kinase II in modulating Antennapedia activity in Drosophila. Genes Dev. 1997;11: 1327–1340. doi: 10.1101/gad.11.10.1327 9171376

38. Gavis ER, Hogness, DS. Phosphorylation, expression and function of the Ultrabithorax protein family in Drosophila melanogaster. Development. 1991;112: 1077–1093. 1682129

39. Stultz BG, Jackson DG, Mortin MA, Yang X, Beachy PA, Hursh DA. Transcriptional activation by extradenticle in the Drosophila visceral mesoderm. Dev Biol. 2006;290: 482–494. doi: 10.1016/j.ydbio.2005.11.041 16403493

40. Krause HM, Klemenz R, Gehring WJ. Expression, modification, and localization of the fushi tarazu protein in Drosophila embryos. Genes Dev. 1988;2: 1021–1036. doi: 10.1101/gad.2.8.1021 3049237

41. Krause HM, Gehring WJ. Stage-specific phosphorylation of the fushi tarazu protein during Drosophila development. EMBO J. 1989;8: 1197–1204. 2743978

42. Bourbon HM, Martin-Blanco E, Rosen D, Kornberg TB. Phosphorylation of the Drosophila engrailed protein at a site outside its homeodomain enhances DNA binding. J Biol Chem. 1995;270: 11130–11139. doi: 10.1074/jbc.270.19.11130 7744743

43. Driever W, Nüsslein-Volhard C. The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo. Nature. 1989;337: 138–143. doi: 10.1038/337138a0 2911348

44. Gay NJ, Poole SJ, Kornberg TB. The Drosophila engrailed protein is phosphorylated by a serine-specific protein kinase. Nucleic Acids Res. 1988;16: 6637–6647. doi: 10.1093/nar/16.14.6637 2899884

45. Ronchi E, Treisman J, Dostatni N, Struhl G, Desplan C. Down-regulation of the Drosophila morphogen Bicoid by the torso-receptor mediated signal transduction cascade. Cell. 1993;74: 347–355. doi: 10.1016/0092-8674(93)90425-p 8343961

46. Dong J, Hung LH, Strome R, Krause HM. A phosphorylation site in the Ftz homeodomain is required for activity. EMBO J. 1998;17: 2308–2318. doi: 10.1093/emboj/17.8.2308 9545243

47. Janody F, Sturny R, Catala F, Desplan C, Dostatni N. Phosphorylation of Bicoid on MAP-kinase sites: contribution to its interaction with the torso pathway. Development. 2000;127: 279–289. 10603346

48. Moazzen H, Rosenfeld R, Percival-Smith A. Non-requirement of a regulatory subunit of Protein Phosphatase 2A, PP2A-B’, for activation of Sex comb reduced activity in Drosophila melanogaster. Mech Dev. 2009;126: 605–610. doi: 10.1016/j.mod.2009.06.1084 19563886

49. Johnson H, Eyers CE. Analysis of Post-translational Modifications by LC-MS/MS. In: Cutillas P, Timms J. (eds) LC-MS/MS in Proteomics. Methods Mol Biol. (Methods and Protocols). Humana Press, Totowa, NJ. 2010. vol. 658. pp. 93–108. doi: 10.1007/978-1-60761-780-8_5

50. Tiefenbach J, Moll PR, Nelson MR, Hu C, Baev L, Kislinger T, et al. A Live Zebrafish-Based Screening System for Human Nuclear Receptor Ligand and Cofactor Discovery. PLoS ONE, 2010;5: 1–12. doi: 10.1371/journal.pone.0009797

51. Studier FW, Moffatt BA. Use of Bacteriophage T7 RNA Polymerase to Direct Selective High-level Expression of Cloned Genes. J Mol Biol. 1986;189: 113–130. doi: 10.1016/0022-2836(86)90385-2 3537305

52. Studier FW, Rosenberg AH, Dunn JJ, Dubendorff JW. Use of T7 RNA Polymerase to Direct Expression of Cloned Genes. Methods Enzymol. 1990;185: 60–89. doi: 10.1016/0076-6879(90)85008-c 2199796

53. Thummel C, Pirrotta V. New pCaSpeR P-element vectors. D. I. S. 1992;71: 150.

54. Rubin GM, Spradling AC. Genetic transformation of Drosophila with transposable element vectors. Science. 1982;218: 348–353. doi: 10.1126/science.6289436 6289436

55. Brand AH, Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993;118: 401–415. 8223268

56. Wieschaus E, Nüsslein-Volhard C. Looking at embryos. In: Roberts DB, editor. Drosophila: A Practical Approach. IRL, Oxford; 1986. pp. 199–228.

57. Loughran ST, Walls D. Purification of Poly-Histidine-Tagged Proteins. Methods Mol Biol. 2011;681: 311–335. doi: 10.1007/978-1-60761-913-0_17 20978973

58. Haneskog L. Purification of Histidine-Tagged Proteins under Denaturing Conditions Using IMAC. CSH Protoc. 2006;2006: pdb.prot4221. doi: 10.1101/pdb.prot4221

59. Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning: A Laboratory Manual. 2nd ed. New York: Cold Spring Harbor Laboratory Press; 1989.

60. Zhang J, Xin L, Shan B, Chen W, Xie M, Yuen D, et al. PEAKS DB: De Novo Sequencing Assisted Database Search for Sensitive and Accurate Peptide Identification. Mol Cell Proteomics. 2012;11: M111.010587. doi: 10.1074/mcp.M111.010587 22186715

61. Humphrey SJ, Azimifar SB, Mann M. High throughput phosphoproteomics reveals in vivo insulin signaling dynamics. Nat Biotechnol. 2015;33: 990–995. doi: 10.1038/nbt.3327 26280412

62. Rappsilber J, Ishihama Y, Mann M. Stop and go extraction tips for Matrix-Assisted Laser Desorption/Ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal Chem. 2003;75: 663–670. doi: 10.1021/ac026117i 12585499

63. Hochuli E, Döbeli H, Schacher A. New metal chelate adsorbent for proteins and peptides containing neighbouring histidine residues. J Chromatogr. 1987;411: 177–184. doi: 10.1016/s0021-9673(00)93969-4 3443622

64. Hochuli E, Bannwarth W, Döbeli H, Gentz R, Stüber D. Genetic approach to facilitate purification of recombinant proteins with a novel metal chelate adsorbent. Nat Biotechnol. 1988;6: 1321–1325. doi: 10.1038/nbt1188-1321

65. Bradford MM. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72: 248–254. doi: 10.1006/abio.1976.9999 942051

66. Merabet S, Dard A. Tracking context-specific transcription factors regulating Hox activity. Dev Dyn. 2014;243: 16–23. doi: 10.1002/dvdy.24002 23794379

67. Wiellette EL, Harding KW, Mace KA, Ronshaugen MR, Wang FY, McGinnis W. spen encodes and RNP motif protein that interacts with Hox pathways to repress the development of head-like sclerites in the Drosophila trunk. Development. 1999:126: 5373–5385. 10556062

68. Billeter M, Qian Y, Otting G, Müller M, Gehring WJ, Wüthrich K. Determination of the three-dimensional structure of the Antennapedia homeodomain from Drosophila in solution by 1H nuclear magnetic resonance spetroscopy. J Mol Biol. 1990;214: 183–197. doi: 10.1016/0022-2836(90)90155-f 2164583

69. Sterck L, Billiau K, Abeel T, Rouzé P, Van de Peer Y. ORCAE: online resource for community annotation of eukaryotes. Nat Methods. 2012;9: 1041. doi: 10.1038/nmeth.2242 23132114

70. Katoh K, Rozewicki J, Yamada KD. MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization. Brief Bioinform. 2019;20: 1160–1166 doi: 10.1093/bib/bbx108 28968734

71. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 2011;7: 539. doi: 10.1038/msb.2011.75 21988835

72. Fisher RA. On the interpretation of χ2 from contingency tables, and the calculation of P. J Royal Stat Soc. 1922;85: 87–94. doi: 10.2307/2340521

73. Artimo P, Jonnalagedda M, Arnold K, Baratin D, Csardi G, de Castro E, et al. ExPASy: SIB bioinformatics resource portal. Nucleic Acids Res. 2012;40: W597–W603. doi: 10.1093/nar/gks400 22661580

74. Gibson G, Schier A, LeMotte P, Gehring WJ. The specificities of Sex combs reduced and Antennapedia are defined by a distinct portion of each protein that includes the homeodomain. Cell. 1990;62: 1087–1103. doi: 10.1016/0092-8674(90)90386-s 1976044

75. Zhao JJ, Lazzarini RA, Pick L. The mouse Hox-1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene. Genes Dev. 1993;7: 343–354. doi: 10.1101/gad.7.3.343 8095481

76. Larsen MR, Thingholm TE, Jensen ON, Roepstorff P, Jørgensen TJD. Highly selective enrichment of phosphorylated peptides from peptide mixtures using titanium dioxide microcolumns. Mol Cell Proteomics. 2005;4: 873–886. doi: 10.1074/mcp.T500007-MCP200 15858219

77. Diella F, Haslam N, Chica C, Budd A, Michael S, Brown NP, et al. Understanding eukaryotic linear motifs and their role in cell signaling and regulation. Front Biosci. 2008;13: 6580–6603. doi: 10.2741/3175 18508681

78. Dinkel H, Michael S, Weatheritt RJ, Davey NE, Van Roey K, Altenberg B, et al. ELM—the database of eukaryotic linear motifs. Nucleic Acids Res. 2012;40: D242–D251. doi: 10.1093/nar/gkr1064 22110040

79. O’Connell NE, Lelli K, Mann RS, Palmer AG 3rd Asparagine deamidation reduces DNA-binding affinity of the Drosophila melanogaster Scr homeodomain. FEBS Lett. 2015;589: 3237–3241. doi: 10.1016/j.febslet.2015.09.020 26435141

80. Zhai B, Villén J, Beausoleil SA, Mintseris J, Gygi SP. Phosphoproteome analysis of Drosophila melanogaster embryos. J Proteome Res. 2008;7: 1675–1682. doi: 10.1021/pr700696a 18327897

81. Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS. Origins of Specificity in Protein-DNA Recognition. Annu Rev Biochem. 2010;79: 233–269. doi: 10.1146/annurev-biochem-060408-091030 20334529

82. Rohs R, West SM, Liu P, Honig B. Nuance in the double-helix and its role in protein-DNA recognition. Curr Opin Struct Biol. 2009;19: 171–177. doi: 10.1016/ 19362815

83. Rohs R, West SM, Sosinsky A, Liu P, Mann RS, Honig B. The role of DNA shape in protein-DNA recognition. Nature. 2009;461: 1248–1253. doi: 10.1038/nature08473 19865164

84. Abe N, Dror I, Yang L, Slattery M, Zhou T, Bussemaker HJ, et al. Deconvolving the recognition of DNA shape from sequence. Cell. 2015;161: 307–318. doi: 10.1016/j.cell.2015.02.008 25843630

85. Passner JM, Ryoo HD, Shen L, Mann RS, Aggarwal AK. Structure of a DNA-bound Ultrabithorax-Extradenticle homeodomain complex. Nature. 1999;397: 714–719. doi: 10.1038/17833 10067897

86. Otting G, Qian YQ, Billeter M, Müller M, Affolter M, Gehring WJ, et al. Protein-DNA contacts in the structure of a homeodomain-DNA complex determined by nuclear magnetic resonance spectroscopy in solution. EMBO J. 1990;9: 3085–3092. doi: 10.1002/j.1460-2075.1990.tb07505.x 1976507

87. Religa TL, Johnson CM, Vu DM, Brewer SH, Dyer RB, Fersht AR. The helix-turn-helix motif as an ultrafast independently folding domain: The pathway of folding of Engrailed homeodomain. Proc Natl Acad Sci U S A. 2007;104: 9272–9277. doi: 10.1073/pnas.0703434104 17517666

88. Jiang T, Zhou X, Taghizadeh K, Dong M, Dedon PC. N-formylation of lysine in histone proteins as a secondary modification arising from oxidative DNA damage. Proc Natl Acad Sci U S A. 2007;104: 60–65. doi: 10.1073/pnas.0606775103 17190813

89. Wiśniewski JR, Zougman A, Mann M. Nε-formylation of lysine is a widespread post-translational modification of nuclear proteins occurring at residues involved in regulation of chromatin function. Nucleic Acids Res. 2008;36: 570–577. doi: 10.1093/nar/gkm1057 18056081

90. Allfrey VG, Faulkner R, Mirsky AE. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc Natl Acad Sci U S A. 1964;51: 786–794. doi: 10.1073/pnas.51.5.786 14172992

91. Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Ann Rev Biochem. 2001;70: 81–120. doi: 10.1146/annurev.biochem.70.1.81 11395403

92. Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell. 1997;90: 595–606. doi: 10.1016/s0092-8674(00)80521-8 9288740

93. Kouzarides T. Acetylation: a regulatory modification to rival phosphorylation? EMBO J. 2000;19: 1176–1179. doi: 10.1093/emboj/19.6.1176 10716917

94. Bannister AJ, Miska EA. Regulation of gene expression by transcription factor acetylation. Cell Mol Life Sci. 2000;57: 1184–1192. doi: 10.1007/pl00000758 11028911

95. Park JM, Jo SH, Kim MY, Kim TH, Ahn YH. Role of transcription factor acetylation in the regulation of metabolic homeostasis. Protein Cell. 2015;6: 804–813. doi: 10.1007/s13238-015-0204-y 26334401

96. Wang C, Tian L, Popov VM, Pestell RG. Acetylation and nuclear receptor action. J Steroid Biochem Mol Biol. 2011;123: 91–100. doi: 10.1016/j.jsbmb.2010.12.003 21167281

97. Glozak MA, Sengupta N, Zhang X, Seto E. Acetylation and deacetylation of non-histone proteins. Gene. 2005;363: 15–23. doi: 10.1016/j.gene.2005.09.010 16289629

98. Choudhary C, Weinert BT, Nishida Y, Verdin E, Mann M. The growing landscape of lysine acetylation links metabolism and cell signalling. Nat Rev Mol Cell Biol. 2014;15: 536–550. doi: 10.1038/nrm3841 25053359

99. Steen H, Jebanathirajah JA, Rush J, Morrice N, Kirschner MW. Phosphorylation analysis by mass spectrometry. Myths, facts, and the consequences for qualitative and quantitative measurements. Mol Cell Proteomics. 2006;5: 172–181. doi: 10.1074/mcp.M500135-MCP200 16204703

100. Hu Y, Sopko R, Chung V, Foos M, Studer RA, Landry SD, et al. iProteinDB: An Integrative Database of Drosophila Post-translational Modifications. G3-Genes Genom Genet. 2019;9: 1–11. doi: 10.1534/g3.118.200637

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