title: An unbiased approach to identify endogenous substrates of "histone" deacetylase 8.
abstract: Despite being extensively characterized structurally and biochemically, the functional role of histone deacetylase 8 (HDAC8) has remained largely obscure due in part to a lack of known cellular substrates. Herein, we describe an unbiased approach using chemical tools in conjunction with sophisticated proteomics methods to identify novel non-histone nuclear substrates of HDAC8, including the tumor suppressor ARID1A. These newly discovered substrates of HDAC8 are involved in diverse biological processes including mitosis, transcription, chromatin remodeling, and RNA splicing and may help guide therapeutic strategies that target the function of HDAC8.
authors.affiliation: Stanley Center for Psychiatric Research, ‡Proteomics Platform, §Cancer Program, and ∥Center for the Science of Therapeutics, Broad Institute of MIT and Harvard , Cambridge, Massachusetts 02142, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Olson
authors.forename: Namrata D
authors.initials: ND
authors.lastname: Udeshi
authors.forename: Noah A
authors.initials: NA
authors.lastname: Wolfson
authors.forename: Carol Ann
authors.initials: CA
authors.lastname: Pitcairn
authors.forename: Eric D
authors.initials: ED
authors.lastname: Sullivan
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Jaffe
authors.forename: Tanya
authors.initials: T
authors.lastname: Svinkina
authors.forename: Ted
authors.initials: T
authors.lastname: Natoli
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Lu
authors.forename: Joshiawa
authors.initials: J
authors.lastname: Paulk
authors.forename: Patrick
authors.initials: P
authors.lastname: McCarren
authors.forename: Florence F
authors.initials: FF
authors.lastname: Wagner
authors.forename: Doug
authors.initials: D
authors.lastname: Barker
authors.forename: Eleanor
authors.initials: E
authors.lastname: Howe
authors.forename: Fanny
authors.initials: F
authors.lastname: Lazzaro
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Gale
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Zhang
authors.forename: Aravind
authors.initials: A
authors.lastname: Subramanian
authors.forename: Carol A
authors.initials: CA
authors.lastname: Fierke
authors.forename: Steven A
authors.initials: SA
authors.lastname: Carr
authors.forename: Edward B
authors.initials: EB
authors.lastname: Holson
mesh_terms: D000107:Acetylation; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D060066:Protein Interaction Maps / Q000187:drug effects*; D040901:Proteomics; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C409470:HDAC8 protein, human; D006655:Histone Deacetylases
references.citation: ChemMedChem. 2014 Mar;9(3):657-64
references.pmid: 24403121
references.citation: Clin Cancer Res. 2009 Jan 1;15(1):91-9
references.pmid: 19118036
references.citation: Am J Transl Res. 2012;4(1):24-43
references.pmid: 22347520
references.citation: Angew Chem Int Ed Engl. 2012 Sep 3;51(36):9083-7
references.pmid: 22890609
references.citation: Bioorg Med Chem. 2010 Jun 1;18(11):4103-10
references.pmid: 20472442
references.citation: J Mol Biol. 2004 Apr 16;338(1):17-31
references.pmid: 15050820
references.citation: Genes Dev. 2009 Jul 15;23(14):1625-30
references.pmid: 19605684
references.citation: Nat Struct Mol Biol. 2013 Feb;20(2):182-7
references.pmid: 23292142
references.citation: Urol Oncol. 2013 Nov;31(8):1770-9
references.pmid: 22944197
references.citation: Biopolymers. 2013 Feb;99(2):112-26
references.pmid: 23175386
references.citation: Oncogene. 2013 Jan 24;32(4):514-27
references.pmid: 22370642
references.citation: Gene. 2005 Dec 19;363:15-23
references.pmid: 16289629
references.citation: Leukemia. 2008 May;22(5):1026-34
references.pmid: 18256683
references.citation: Int J Biochem Cell Biol. 2009 Jan;41(1):185-98
references.pmid: 18804549
references.citation: Oncol Rep. 2011 Jun;25(6):1677-81
references.pmid: 21455583
references.citation: Science. 2009 Aug 14;325(5942):834-40
references.pmid: 19608861
references.citation: Mol Cell. 2013 Dec 26;52(6):769-82
references.pmid: 24268577
references.citation: Mol Pharmacol. 2005 Oct;68(4):917-32
references.pmid: 15955865
references.citation: Sci Signal. 2011 Jul 26;4(183):ra48
references.pmid: 21791702
references.citation: Biochem J. 2000 Aug 15;350 Pt 1:199-205
references.pmid: 10926844
references.citation: Nature. 2012 Sep 13;489(7415):313-7
references.pmid: 22885700
references.citation: Mol Endocrinol. 2010 Jul;24(7):1349-58
references.pmid: 20484414
references.citation: Neoplasia. 2012 Oct;14(10):986-93
references.pmid: 23097632
references.citation: Mol Cell. 2008 Jul 11;31(1):143-51
references.pmid: 18614053
references.citation: J Med Chem. 2012 Nov 26;55(22):9562-75
references.pmid: 23116147
references.citation: Annu Rev Pharmacol Toxicol. 2013;53:311-30
references.pmid: 23294310