Proteome and Acetylome Analysis Identifies Novel Pathways and Targets Regulated by Perifosine in Neuroblastoma.
Proteome and Acetylome Analysis Identifies Novel Pathways and Targets Regulated by Perifosine in Neuroblastoma.
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蛋白质组和乙酰组分析确定了神经母细胞瘤中哌立福辛调节的新途径和靶点。
DOI：
10.1038/srep42062
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发表时间：
2017-02-06
影响因子：
4.6
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Gu X;Hua Z;Dong Y;Zhan Y;Zhang X;Tian W;Liu Z;Thiele CJ;Li Z
Akt抑制剂Perifosine已被证明在控制神经母细胞瘤肿瘤生长方面有效。然而，研究表明，除了抑制Akt的能力外，还有其他机制有助于酪氨酸的抗肿瘤活性。为了深入了解草氨酸在神经母细胞瘤中的抗肿瘤活性，我们利用SILAC标记、亲和富集、高分辨率和LC-MS/MS分析研究了草氨酸治疗SK-N-AS神经母细胞瘤细胞后蛋白质组和乙酰组的变化。生物信息学分析结果表明，SK-N-AS细胞共检测到5880个蛋白和3415个赖氨酸乙酰化位点，获得216个差异表达蛋白和115个差异表达赖氨酸乙酰化位点。这些差异表达蛋白和赖氨酸乙酰化蛋白参与了许多不同的生物学功能、代谢途径和病理生理过程。本研究详细介绍了酪氨酸对SK-N-AS细胞中蛋白质组和赖氨酸乙酰组的影响，并扩展了我们对酪氨酸在神经母细胞瘤中的作用机制的理解。
Perifosine, an Akt inhibitor, has been shown to be effective in controlling neuroblastoma tumor growth. However, studies indicate that in addition to the ability to inhibit Akt, other mechanisms contribute to perifosine’s anti-tumor activity. To gain insight into perifosine anti-tumor activity in neuroblastoma we have studied changes in the proteome and acetylome after perifosine treatment in SK-N-AS neuroblastoma cells using SILAC labeling, affinity enrichment, high-resolution and LC-MS/MS analysis. Bioinformatic analysis indicates that, a total of 5,880 proteins and 3,415 lysine acetylation sites were quantified in SK-N-AS cells and 216 differentially expressed proteins and 115 differentially expressed lysine acetylation sites were obtained. These differentially expressed proteins and lysine acetylated proteins were involved in a number of different biological functions, metabolic pathways and pathophysiological processes. This study details the impact of perifosine on proteome and lysine acetylome in SK-N-AS cells and expands our understanding of the mechanisms of perifosine action in neuroblastoma.