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Global Analysis of Lysine 2-Hydroxyisobutyrylome upon SAHA Treatment and Its Relationship with Acetylation and Crotonylation
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2018-08-21 , DOI: 10.1021/acs.jproteome.8b00289
Quan Wu 1, 2 , Li Ke 3 , Chi Wang 1 , Pingsheng Fan 4 , Zhiwei Wu 1 , Xiaoling Xu 5
Affiliation  

Lysine 2-hydroxyisobutyrylation is a newly discovered protein acylation and was reported to share acyltransferases and deacylases with the widely studied lysine acetylation. The well-known acetyltransferase Tip60 and histone deacetylases HDAC 2 and HDAC 3 were discovered to be “writer” and “eraser” of this new PTM on histones. However, the acyltransferases and deacylases for nonhistone proteins are still unclear. In this work, lysine 2-hydroxyisobutyrylome on both histones and nonhistone proteins upon SAHA treatment were intensively studied and 8765 lysine 2-hydroxyisobutyrylation sites on 2484 proteins were identified in A549 cells. This is the largest data set of lysine 2-hydroxyisobutyrylome in mammalian cells to date. It was found that lysine 2-hydroxyisobutyrylation participates in varieties of biological functions and processes including ribosome, glycolysis/gluconeogenesis, and transcription. More importantly, it was found that most quantified sites on core histones were up-regulated upon SAHA treatment for all 2-hydroxyisobutyrylation, crotonylation, and acetylation and the fold changes upon SAHA of 2-hydroxyisobutyrylation and crotonylation on nonhistone proteins were highly correlated, while their fold changes have little correlations with acetylation on nonhistone proteins.

中文翻译:

SAHA治疗后赖氨酸2-羟基异丁酰基团的整体分析及其与乙酰化和巴豆酰化的关系

赖氨酸2-羟基异丁酰化是一种新发现的蛋白质酰化作用,据报道与赖氨酸乙酰化作用相同,可共享酰基转移酶和脱酰基酶。发现众所周知的乙酰基转移酶Tip60和组蛋白脱乙酰基酶HDAC 2和HDAC 3是这种新的PTM组蛋白的“书写者”和“擦除者”。但是,对于非组蛋白的酰基转移酶和脱酰基酶仍不清楚。在这项工作中,深入研究了SAHA处理后组蛋白和非组蛋白上的赖氨酸2-羟基异丁酰化,在A549细胞中鉴定了2484个蛋白上的8765个赖氨酸2-羟基异丁酰化位点。这是迄今为止哺乳动物细胞中最大的赖氨酸2-羟基异丁酰组数据集。发现赖氨酸2-羟基异丁酰化参与多种生物学功能和过程,包括核糖体,糖酵解/糖异生和转录。更重要的是,发现在SAHA处理后,核心组蛋白上的大多数定量位点都被上调了所有2-羟基异丁酰化,巴豆酰化和乙酰化作用,而SAHA上非组蛋白蛋白上2-羟基异丁酰化和巴豆酰化的倍数变化高度相关,而它们的倍数变化与非组蛋白的乙酰化几乎没有关系。
更新日期:2018-08-21
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