蛋白质磷酸化是一种广泛发生且重要的翻译后修饰，是各种生物过程不可或缺的一部分。我们之前使用蛋白质亲和探针来识别顺铂损伤的基因，发现顺铂对蛋白激酶和蛋白磷酸酶基因造成严重损伤。在这项研究中，我们研究了顺铂诱导的 A549 细胞整体蛋白质组和磷酸蛋白质组的变化。使用 Fe-IMAC 珠子和酪氨酸磷酸化富集抗体，我们在顺铂处理的 A549 细胞和对照细胞的三个生物复制中鉴定了 6944 个蛋白质组和 4915 个蛋白质上的 18,274 个磷酸化位点。其中，鉴定出 730 个酪氨酸磷酸化位点，这是顺铂治疗后 A549 细胞中此类位点的最实质性发现。生物信息学分析表明，表现出显着磷酸化水平变化的蛋白质主要涉及RNA加工、修饰、转录、翻译和剪接体。这表明顺铂诱导的蛋白激酶和磷酸酶损伤可能会破坏这些蛋白的正常功能，从而损害 DNA 复制、RNA 翻译和剪切，最终导致肿瘤细胞死亡。此外，我们将蛋白质组数据与之前获得的顺铂损伤基因进行交叉引用，观察到大多数下调的蛋白质源自顺铂诱导的基因损伤。这些数据可在 ProteomeXchange 上获取，标识符为 PXD053902。版权所有 © 2024 Elsevier Inc。保留所有权利。

Protein phosphorylation, a widely occurring and significant post-translational modification, is integral to various biological processes. We previously utilized a protein affinity probe to identify genes damaged by cisplatin, revealing that it inflicts substantial damage on protein kinase and protein phosphatase genes. In this study, we investigated cisplatin-induced alterations in the global proteome and phosphoproteome of A549 cells. Employing Fe-IMAC beads and tyrosine phosphorylation enrichment antibodies, we identified 6944 protein groups and 18,274 phosphorylation sites on 4915 proteins across three biological replicates of both cisplatin-treated A549 cells and control cells. Among these, 730 tyrosine phosphorylation sites were identified-marking the most substantial discovery of such sites in A549 cells following cisplatin treatment. Bioinformatics analysis indicated that the proteins exhibiting significant phosphorylation level changes predominantly involved in RNA processing, modification, transcription, translation, and the spliceosome. This suggests that cisplatin-induced damage to protein kinases and phosphatases may disrupt the normal function of these proteins, consequently impairing DNA replication, RNA translation, and shearing, ultimately culminating in tumor cell death. Moreover, we cross-referenced our proteomic data with our previously obtained cisplatin-damaged genes, observing that the majority of down-regulated proteins derived from cisplatin-induced gene damage. The data are available on ProteomeXchange under the identifier PXD053902.Copyright © 2024 Elsevier Inc. All rights reserved.