Quantitative Analysis of Global Proteome and Lysine Acetylome Reveal the Differential Impacts of VPA and SAHA on HL60 Cells

整体蛋白质组和赖氨酸乙酰基组的定量分析揭示了 VPA 和 SAHA 对 HL60 细胞的不同影响

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作者:Xiaoyu Zhu, Xin Liu, Zhongyi Cheng, Jun Zhu, Lei Xu, Fengsong Wang, Wulin Qi, Jiawei Yan, Ning Liu, Zimin Sun, Huilan Liu, Xiaojun Peng, Yingchan Hao, Nan Zheng, Quan Wu

Abstract

Valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) are both HDAC inhibitors (HDACi). Previous studies indicated that both inhibitors show therapeutic effects on acute myeloid leukaemia (AML), while the differential impacts of the two different HDACi on AML treatment still remains elusive. In this study, using 3-plex SILAC based quantitative proteomics technique, anti-acetyllysine antibody based affinity enrichment, high resolution LC-MS/MS and intensive bioinformatic analysis, the quantitative proteome and acetylome in SAHA and VPA treated AML HL60 cells were extensively studied. In total, 5,775 proteins and 1,124 lysine acetylation sites were successfully obtained in response to VAP and SAHA treatment. It is found that VPA and SAHA treatment differently induced proteome and acetylome profiling in AML HL60 cells. This study revealed the differential impacts of VPA and SAHA on proteome/acetylome in AML cells, deepening our understanding of HDAC inhibitor mediated AML therapeutics.

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