Unraveling Lysine Deacetylase Inhibitor Specificities for Endogenous Acetylation Sites

Data from ProteomeXchange: PXD ID: PXD001377. Experiment: Bufexamacproteome_hs_LH, file: 20120521_QE3_LC2_CHS_SA_Bufexamacproteome_03.mzml. From ProteomeXchange: {{i}} Lysine deacetylases (KDACs) are important regulators of biological processes. KDAC inhibitors (KDACIs) are important tools for basic research and attractive therapeutic candidates, yet their effects on in-vivo acetylation sites are poorly known. Here we obtained acetylation signatures for 19 different KDACIs that cover all known deacetylases. Most KDACIs targeting non-sirtuin deacetylases increased acetylation of a small, but specific, subset of the acetylome, and included sites on histone and other chromatin-associated proteins. Using a combination of genetic deletion and inhibitor treatment we found that the sirtuin inhibitor nicotinamide increased acetylation via SIRT1 inhibition, whereas tubacin and bufexamac affected cytoplasmic proteins through inhibition of HDAC6 ... {{/i}}

数据来自蛋白质组交换库（ProteomeXchange）：PXD编号为PXD001377。实验名称为Bufexamacproteome_hs_LH，所用文件为20120521_QE3_LC2_CHS_SA_Bufexamacproteome_03.mzml。源自蛋白质组交换库（ProteomeXchange）：{{i}}赖氨酸脱乙酰酶（Lysine deacetylases, KDACs）是生物过程的重要调控因子。赖氨酸脱乙酰酶抑制剂（KDAC inhibitors, KDACIs）既是基础研究中的关键工具，亦是极具吸引力的治疗候选药物，但目前学界对其在体内乙酰化位点的调控效应仍知之甚少。本研究获取了覆盖所有已知脱乙酰酶的19种不同KDACIs的乙酰化特征谱。多数靶向非沉默信息调节因子（sirtuin）家族脱乙酰酶的KDACIs，可使乙酰化组中一个较小但具有特异性的子集发生乙酰化水平上调，这些位点涵盖组蛋白及其他染色质相关蛋白。结合基因敲除与抑制剂处理实验，我们发现沉默信息调节因子抑制剂烟酰胺（nicotinamide）通过抑制SIRT1提升乙酰化水平，而tubacin与bufexamac则通过抑制组蛋白脱乙酰酶6（HDAC6）对胞质蛋白产生乙酰化调控作用……{{/i}}