Department of Clinical Science, Faculty of Medicine, University of Bergen, Jonas Lies vei 87, N-5021 Bergen, Norway.
The Proteomics Unit at the University of Bergen, Department of Biomedicine, Building for Basic Biology, Faculty of Medicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway.
Curr Med Chem. 2019;26(28):5317-5337. doi: 10.2174/0929867326666190503164004.
Post-translational modification (PTM) crosstalk is a young research field. However, there is now evidence of the extraordinary characterization of the different proteoforms and their interactions in a biological environment that PTM crosstalk studies can describe. Besides gene expression and phosphorylation profiling of acute myeloid leukemia (AML) samples, the functional combination of several PTMs that might contribute to a better understanding of the complexity of the AML proteome remains to be discovered.
By reviewing current workflows for the simultaneous enrichment of several PTMs and bioinformatics tools to analyze mass spectrometry (MS)-based data, our major objective is to introduce the PTM crosstalk field to the AML research community.
After an introduction to PTMs and PTM crosstalk, this review introduces several protocols for the simultaneous enrichment of PTMs. Two of them allow a simultaneous enrichment of at least three PTMs when using 0.5-2 mg of cell lysate. We have reviewed many of the bioinformatics tools used for PTM crosstalk discovery as its complex data analysis, mainly generated from MS, becomes challenging for most AML researchers. We have presented several non-AML PTM crosstalk studies throughout the review in order to show how important the characterization of PTM crosstalk becomes for the selection of disease biomarkers and therapeutic targets.
Herein, we have reviewed the advances and pitfalls of the emerging PTM crosstalk field and its potential contribution to unravel the heterogeneity of AML. The complexity of sample preparation and bioinformatics workflows demands a good interaction between experts of several areas.
翻译后修饰（PTM）串扰是一个年轻的研究领域。然而，现在有证据表明，不同的翻译后修饰蛋白及其在生物环境中的相互作用具有非凡的特征，PTM 串扰研究可以描述这些特征。除了对急性髓系白血病（AML）样本进行基因表达和磷酸化分析外，还需要发现几种翻译后修饰的功能组合，这可能有助于更好地理解 AML 蛋白质组的复杂性。
通过回顾同时富集几种翻译后修饰的当前工作流程和用于分析基于质谱（MS）数据的生物信息学工具，我们的主要目标是将 PTM 串扰领域介绍给 AML 研究界。
在介绍翻译后修饰和 PTM 串扰之后，本综述介绍了几种同时富集 PTM 的方案。其中有两种方案在使用 0.5-2mg 细胞裂解物时，可以同时富集至少三种翻译后修饰。我们已经回顾了许多用于 PTM 串扰发现的生物信息学工具，因为其复杂的数据分析主要来自 MS，这对大多数 AML 研究人员来说具有挑战性。在整个综述中，我们展示了一些非 AML PTM 串扰研究，以表明翻译后修饰串扰的特征对于疾病生物标志物和治疗靶点的选择变得多么重要。
本文综述了新兴的 PTM 串扰领域的进展和陷阱及其对揭示 AML 异质性的潜在贡献。样品制备和生物信息学工作流程的复杂性要求来自多个领域的专家进行良好的互动。
