title: Quantitative Analysis of Global Proteome and Lysine Acetylome Reveal the Differential Impacts of VPA and SAHA on HL60 Cells.
abstract: Valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) are both HDAC inhibitors (HDACi). Previous studies indicated that both inhibitors show therapeutic effects on acute myeloid leukaemia (AML), while the differential impacts of the two different HDACi on AML treatment still remains elusive. In this study, using 3-plex SILAC based quantitative proteomics technique, anti-acetyllysine antibody based affinity enrichment, high resolution LC-MS/MS and intensive bioinformatic analysis, the quantitative proteome and acetylome in SAHA and VPA treated AML HL60 cells were extensively studied. In total, 5,775 proteins and 1,124 lysine acetylation sites were successfully obtained in response to VAP and SAHA treatment. It is found that VPA and SAHA treatment differently induced proteome and acetylome profiling in AML HL60 cells. This study revealed the differential impacts of VPA and SAHA on proteome/acetylome in AML cells, deepening our understanding of HDAC inhibitor mediated AML therapeutics.
authors.affiliation: Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Translational Medcine Advanced Institute, Tongji University, No.1239, Siping Road, Shanghai, 200092, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Jingjie PTM Biolab (Hangzhou) Co. Ltd, Hangzhou 310018, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of orthopaedics, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: School of Life science, Anhui Medical University, Hefei, 230032, China.
authors.forename: Fengsong
authors.initials: F
authors.lastname: Wang
authors.affiliation: Jingjie PTM Biolab (Hangzhou) Co. Ltd, Hangzhou 310018, China.
authors.forename: Wulin
authors.initials: W
authors.lastname: Qi
authors.affiliation: Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Zimin
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Huilan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Jingjie PTM Biolab (Hangzhou) Co. Ltd, Hangzhou 310018, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Peng
authors.affiliation: Central Laboratory of Medical Research Centre, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Yingchan
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Central Laboratory of Medical Research Centre, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Central Laboratory of Medical Research Centre, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000107:Acetylation; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D018922:HL-60 Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D056510:Position-Specific Scoring Matrices; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D014635:Valproic Acid / Q000494:pharmacology*; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D020543:Proteome; D000077337:Vorinostat; D014635:Valproic Acid; D008239:Lysine
references.citation: EMBO J. 2001 Dec 17;20(24):6969-78
references.pmid: 11742974
references.citation: Nat Rev Drug Discov. 2014 Sep;13(9):673-91
references.pmid: 25131830
references.citation: Nat Biotechnol. 2015 Apr;33(4):415-23
references.pmid: 25751058
references.citation: J Clin Oncol. 2007 Jul 20;25(21):3109-15
references.pmid: 17577020
references.citation: Nature. 2002 Jul 11;418(6894):195-9
references.pmid: 12110891
references.citation: Blood. 2010 Nov 25;116(22):4422-9
references.pmid: 20668231
references.citation: J Proteome Res. 2014 Jul 3;13(7):3294-302
references.pmid: 24874924
references.citation: Lancet. 2006 Nov 25;368(9550):1894-907
references.pmid: 17126723
references.citation: Cell Death Differ. 1999 Jun;6(6):497-507
references.pmid: 10381652
references.citation: Curr Opin Genet Dev. 2003 Apr;13(2):136-42
references.pmid: 12672490
references.citation: Cell Motil Cytoskeleton. 1999;42(3):241-55
references.pmid: 10098937
references.citation: Cancer Res. 2001 Dec 1;61(23):8492-7
references.pmid: 11731433
references.citation: Biochem J. 2003 Mar 15;370(Pt 3):737-49
references.pmid: 12429021
references.citation: Nat Rev Cancer. 2006 Jan;6(1):38-51
references.pmid: 16397526
references.citation: Gynecol Oncol. 2014 Jun;133(3):599-606
references.pmid: 24631446
references.citation: Curr Protoc Bioinformatics. 2011 Sep;Chapter 13:Unit 13.15-24
references.pmid: 21901740
references.citation: Sci Rep. 2015;5:9520
references.pmid: 25825284
references.citation: Genome Res. 2003 Nov;13(11):2498-504
references.pmid: 14597658
references.citation: Nat Rev Drug Discov. 2012 May;11(5):384-400
references.pmid: 22498752
references.citation: Cancer Res. 2005 Dec 1;65(23):11136-45
references.pmid: 16322264
references.citation: Cancer Res. 2005 Jul 15;65(14):6321-9
references.pmid: 16024634
references.citation: Anticancer Res. 2008 May-Jun;28(3A):1585-91
references.pmid: 18630516
references.citation: Exp Hematol. 2005 Jan;33(1):53-61
references.pmid: 15661398
references.citation: Nat Rev Cancer. 2004 Feb;4(2):133-42
references.pmid: 14964309
references.citation: Leuk Res. 2002 May;26(5):495-502
references.pmid: 11916526
references.citation: Mol Cell Proteomics. 2004 Sep;3(9):908-19
references.pmid: 15238601
references.citation: Blood. 2006 Nov 15;108(10):3271-9
references.pmid: 16882711
references.citation: Trends Biochem Sci. 2011 Feb;36(2):108-16
references.pmid: 20934340
references.citation: Cancer. 2006 Mar 1;106(5):1090-8
references.pmid: 16435386
references.citation: Mol Cell Proteomics. 2002 May;1(5):376-86
references.pmid: 12118079
references.citation: Nat Med. 2005 Jan;11(1):71-6
references.pmid: 15619634
references.citation: Oncol Rep. 2006 Jan;15(1):187-91
references.pmid: 16328054
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W169-75
references.pmid: 17576678
references.citation: Nat Rev Drug Discov. 2006 Sep;5(9):769-84
references.pmid: 16955068
references.citation: J Proteome Res. 2014 Dec 5;13(12):6087-95
references.pmid: 25377623
references.citation: Nat Rev Cancer. 2001 Dec;1(3):194-202
references.pmid: 11902574
references.citation: Bioinformatics. 2009 Jun 15;25(12):i110-8
references.pmid: 19477976
references.citation: Science. 2009 Aug 14;325(5942):834-40
references.pmid: 19608861
references.citation: N Engl J Med. 1999 Sep 30;341(14):1051-62
references.pmid: 10502596
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W182-5
references.pmid: 17526522
references.citation: Blood. 2004 Sep 1;104(5):1266-9
references.pmid: 15155466
references.citation: Mol Cell Proteomics. 2012 Oct;11(10):1048-62
references.pmid: 22826441
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3921-6
references.pmid: 15001702
references.citation: Cancer. 2011 Oct 1;117(19):4424-38
references.pmid: 21491416
references.citation: J Clin Oncol. 2007 Sep 1;25(25):3884-91
references.pmid: 17679729
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W585-7
references.pmid: 17517783
references.citation: Cancer Res. 2013 Dec 15;73(24):7265-76
references.pmid: 24158093
references.citation: Blood. 2003 Apr 15;101(8):3236-9
references.pmid: 12446442
references.citation: J Proteome Res. 2010 Feb 5;9(2):1129-37
references.pmid: 20050688
references.citation: Int J Cancer. 2007 Aug 1;121(3):656-65
references.pmid: 17417771
references.citation: BMC Proc. 2009 Jul 16;3 Suppl 4:S10
references.pmid: 19615110
references.citation: Oncogene. 2009 Apr 9;28(14):1653-68
references.pmid: 19234488
references.citation: Cancer Chemother Pharmacol. 2007 Jul;60(2):245-55
references.pmid: 17096161