Dunphy Katie, Dowling Paul, Bazou Despina, O'Gorman Peter
Department of Biology, National University of Ireland, W23 F2K8 Maynooth, Ireland.
Department of Haematology, Mater Misericordiae University Hospital, D07 WKW8 Dublin, Ireland.
Cancers (Basel). 2021 Apr 16;13(8):1930. doi: 10.3390/cancers13081930.
Post-translational modifications (PTMs) add a layer of complexity to the proteome through the addition of biochemical moieties to specific residues of proteins, altering their structure, function and/or localization. Mass spectrometry (MS)-based techniques are at the forefront of PTM analysis due to their ability to detect large numbers of modified proteins with a high level of sensitivity and specificity. The low stoichiometry of modified peptides means fractionation and enrichment techniques are often performed prior to MS to improve detection yields. Immuno-based techniques remain popular, with improvements in the quality of commercially available modification-specific antibodies facilitating the detection of modified proteins with high affinity. PTM-focused studies on blood cancers have provided information on altered cellular processes, including cell signaling, apoptosis and transcriptional regulation, that contribute to the malignant phenotype. Furthermore, the mechanism of action of many blood cancer therapies, such as kinase inhibitors, involves inhibiting or modulating protein modifications. Continued optimization of protocols and techniques for PTM analysis in blood cancer will undoubtedly lead to novel insights into mechanisms of malignant transformation, proliferation, and survival, in addition to the identification of novel biomarkers and therapeutic targets. This review discusses techniques used for PTM analysis and their applications in blood cancer research.
翻译后修饰（PTMs）通过向蛋白质的特定残基添加生化基团，为蛋白质组增添了一层复杂性，改变了它们的结构、功能和/或定位。基于质谱（MS）的技术处于PTM分析的前沿，因为它们能够以高灵敏度和特异性检测大量修饰蛋白。修饰肽的低化学计量意味着在质谱分析之前通常要进行分级分离和富集技术，以提高检测产量。基于免疫的技术仍然很受欢迎，市售的修饰特异性抗体质量的提高有助于高亲和力地检测修饰蛋白。针对血液癌症的PTM重点研究提供了有关细胞过程改变的信息，包括细胞信号传导、细胞凋亡和转录调控，这些过程导致了恶性表型。此外，许多血液癌症疗法（如激酶抑制剂）的作用机制涉及抑制或调节蛋白质修饰。持续优化血液癌症中PTM分析的方案和技术无疑将带来对恶性转化、增殖和存活机制的新见解，此外还能识别新的生物标志物和治疗靶点。本综述讨论了用于PTM分析的技术及其在血液癌症研究中的应用。
