An Unbiased Approach To Identify Endogenous Substrates of "Histone" Deacetylase 8

作者:Olson David E; Udeshi Namrata D; Wolfson Noah A; Pitcairn Carol Ann; Sullivan Eric D; Jaffe Jacob D; Svinkina Tanya; Natoli Ted; Lu Xiaodong; Paulk Joshiawa; McCarren Patrick; Wagner Florence F; Barker Doug; Howe Eleanor; Lazzaro Fanny; Gale Jennifer P; Zhang Yan Ling; Subramanian Aravind; Fierke Carol A; Carr Steven A; Holson Edward B*
来源:ACS Chemical Biology, 2014, 9(10): 2210-2216.
DOI:10.1021/cb500492r

摘要

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.

  • 出版日期2014-10