Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI, 48202, USA.
Chembiochem. 2019 Jun 3;20(11):1444-1449. doi: 10.1002/cbic.201800797. Epub 2019 Apr 25.
Histone deacetylase 1 (HDAC1) regulates transcription by deacetylating histones. In addition to histones, several non-histone proteins are HDAC1 substrates, which suggests a role for HDAC1 beyond epigenetics. Unfortunately, the identification of non-histone substrates has been largely serendipitous, which makes full characterization of HDAC1 functions difficult. To overcome this challenge, inactive "trapping" mutants were recently developed to identify HDAC1 substrates. To optimize substrate trapping, the relative trapping abilities of 17 inactive HDAC1 mutants was assessed. HDAC1 H141A, F150A, and C151A showed strong binding to substrates LSD1 and p53. Interestingly, each mutant preferentially trapped a different substrate. By combining several inactive mutants, the trapping strategy will facilitate the discovery of new HDAC1 substrates and shed light on the variety of HDAC1-related functions in cell biology.
组蛋白去乙酰化酶 1（HDAC1）通过去乙酰化组蛋白来调节转录。除了组蛋白，几种非组蛋白蛋白也是 HDAC1 的底物，这表明 HDAC1 的作用超出了表观遗传学。不幸的是，非组蛋白底物的鉴定在很大程度上是偶然的，这使得 HDAC1 功能的全面表征变得困难。为了克服这一挑战，最近开发了无活性的“捕获”突变体来鉴定 HDAC1 的底物。为了优化底物的捕获，评估了 17 种无活性 HDAC1 突变体的相对捕获能力。HDAC1 H141A、F150A 和 C151A 与 LSD1 和 p53 底物具有很强的结合能力。有趣的是，每种突变体都优先捕获不同的底物。通过结合几种无活性的突变体，该捕获策略将有助于发现新的 HDAC1 底物，并阐明细胞生物学中与 HDAC1 相关的各种功能。
