title: Acetylation of RNA processing proteins and cell cycle proteins in mitosis.
abstract: Mitosis is a highly regulated process in which errors can lead to genomic instability, a hallmark of cancer. During this phase of the cell cycle, transcription is silent and RNA translation is inhibited. Thus, mitosis is largely driven by post-translational modification of proteins, including phosphorylation, methylation, ubiquitination, and sumoylation. Here, we show that protein acetylation is prevalent during mitosis. To identify proteins that are acetylated, we synchronized HeLa cells in early prometaphase and immunoprecipitated lysine-acetylated proteins with antiacetyl-lysine antibody. The immunoprecipitated proteins were identified by LC-ESI-MS/MS analysis. These include proteins involved in RNA translation, RNA processing, cell cycle regulation, transcription, chaperone function, DNA damage repair, metabolism, immune response, and cell structure. Immunoprecipitation followed by Western blot analyses confirmed that two RNA processing proteins, eIF4G and RNA helicase A, and several cell cycle proteins, including APC1, anillin, and NudC, were acetylated in mitosis. We further showed that acetylation of APC1 and NudC was enhanced by apicidin treatment, suggesting that their acetylation was regulated by histone deacetylase. Moreover, treating mitotic cells with apicidin or trichostatin A induced spindle abnormalities and cytokinesis failure. These studies suggest that protein acetylation/deacetylation is likely an important regulatory mechanism in mitosis.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Chuang
authors.forename: Sue-Hwa
authors.initials: SH
authors.lastname: Lin
authors.forename: Feilei
authors.initials: F
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Djuro
authors.initials: D
authors.lastname: Josic
authors.forename: Li-yuan
authors.initials: LY
authors.lastname: Yu-Lee
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D048749:Cytokinesis / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D015151:Immunoblotting; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D040901:Proteomics; D012323:RNA Processing, Post-Transcriptional; D013347:Subcellular Fractions / Q000737:chemistry; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D006877:Hydroxamic Acids; D010456:Peptides, Cyclic; D014404:Tubulin; C102351:apicidin; C012589:trichostatin A; D004247:DNA
references.citation: Electrophoresis. 2009 Apr;30(7):1168-74
references.pmid: 19294690
references.citation: J Biol Chem. 2005 Sep 30;280(39):33516-24
references.pmid: 16040610
references.citation: Gene. 2001 Jan 10;262(1-2):51-9
references.pmid: 11179667
references.citation: Nat Rev Drug Discov. 2006 Sep;5(9):769-84
references.pmid: 16955068
references.citation: Cell Mol Life Sci. 2008 Oct;65(19):3100-9
references.pmid: 18759129
references.citation: Int J Dev Biol. 2001 Oct;45(7):839-43
references.pmid: 11732844
references.citation: Electrophoresis. 2009 Oct;30(20):3636-46
references.pmid: 19768705
references.citation: FEBS Lett. 1992 Jan 13;296(1):82-6
references.pmid: 1730297
references.citation: Biochem Soc Trans. 2008 Jun;36(Pt 3):405-10
references.pmid: 18481969
references.citation: Cell Mol Life Sci. 2007 Mar;64(5):589-600
references.pmid: 17334950
references.citation: J Biol Chem. 1997 Apr 25;272(17):11487-94
references.pmid: 9111062
references.citation: Int J Biochem Cell Biol. 2009 Jan;41(1):185-98
references.pmid: 18804549
references.citation: Cell. 2007 Feb 23;128(4):693-705
references.pmid: 17320507
references.citation: Curr Biol. 2006 Jul 25;16(14):1414-21
references.pmid: 16860740
references.citation: Oncogene. 2008 Feb 28;27(10):1345-54
references.pmid: 17828304
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2543-8
references.pmid: 19181856
references.citation: Cancer Biol Ther. 2005 Feb;4(2):197-206
references.pmid: 15753652
references.citation: Mol Cell Biol. 2007 Oct;27(19):6639-46
references.pmid: 17664278
references.citation: J Cell Sci. 2009 Apr 15;122(Pt 8):1071-9
references.pmid: 19339546
references.citation: Curr Protoc Cell Biol. 2001 May;Chapter 8:Unit 8.4
references.pmid: 18228389
references.citation: J Proteome Res. 2009 Oct;8(10):4553-63
references.pmid: 19691289
references.citation: Biochim Biophys Acta. 2008 Sep;1786(1):49-59
references.pmid: 18544349
references.citation: J Neurosci. 2001 Dec 15;21(24):RC187
references.pmid: 11734602
references.citation: Science. 2009 Aug 14;325(5942):834-40
references.pmid: 19608861
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4179-84
references.pmid: 18326024
references.citation: Nat Rev Mol Cell Biol. 2004 Mar;5(3):232-41
references.pmid: 14991003
references.citation: Dev Cell. 2003 Jul;5(1):127-38
references.pmid: 12852857
references.citation: Oncogene. 2009 Jul 23;28(29):2654-66
references.pmid: 19483727
references.citation: Mol Cell Biol. 1998 Jan;18(1):468-76
references.pmid: 9418894
references.citation: Biochem J. 2008 Jan 15;409(2):581-9
references.pmid: 17868033
references.citation: J Biol Chem. 2009 Mar 27;284(13):8223-7
references.pmid: 19008217
references.citation: Biochemistry. 2005 Sep 20;44(37):12265-72
references.pmid: 16156639
references.citation: Curr Opin Cell Biol. 2009 Jun;21(3):444-51
references.pmid: 19285851
references.citation: Science. 2009 Mar 13;323(5920):1477-81
references.pmid: 19286556
references.citation: Biochem Soc Trans. 2008 Jun;36(Pt 3):439-41
references.pmid: 18481976
references.citation: Cancer Res. 2007 Jul 1;67(13):6360-7
references.pmid: 17616695
references.citation: J Biol Chem. 2005 May 13;280(19):18610-22
references.pmid: 15755734
references.citation: Mol Cell. 2006 Aug;23(4):607-18
references.pmid: 16916647
references.citation: Nat Rev Mol Cell Biol. 2006 Sep;7(9):644-56
references.pmid: 16896351
references.citation: EMBO J. 2009 Jul 22;28(14):2077-89
references.pmid: 19407811
references.citation: Cell. 2009 Feb 6;136(3):447-60
references.pmid: 19203580
references.citation: Oncogene. 2007 Aug 13;26(37):5541-52
references.pmid: 17694093
references.citation: Mol Cell. 2008 Aug 22;31(4):449-461
references.pmid: 18722172
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7
references.pmid: 18669648
references.citation: Cell Cycle. 2008 Mar 15;7(6):741-4
references.pmid: 18239464
references.citation: Cytometry. 1987 Jan;8(1):1-8
references.pmid: 3803091
references.citation: Gene. 2006 Feb 15;367:17-37
references.pmid: 16337753
references.citation: Nature. 2002 May 23;417(6887):455-8
references.pmid: 12024216
references.citation: J Cell Sci. 2003 May 15;116(Pt 10):1991-2003
references.pmid: 12679384
references.citation: Oncogene. 2005 Mar 3;24(10):1653-62
references.pmid: 15744326
references.citation: Biochimie. 2005 Sep-Oct;87(9-10):805-11
references.pmid: 15951098
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2795-800
references.pmid: 9501169
references.citation: Cell Cycle. 2005 May;4(5):717-26
references.pmid: 15846093