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Mass spectrometry-based proteomics analyses of post-translational modifications and proteoforms in human pituitary adenomas
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics ( IF 2.5 ) Pub Date : 2020-12-13 , DOI: 10.1016/j.bbapap.2020.140584
Jiajia Li 1 , Xianquan Zhan 2
Affiliation  

Pituitary adenoma (PA) is a common intracranial neoplasm, which affects the hypothalamus-pituitary-target organ axis systems, and is hazardous to human health. Post-translational modifications (PTMs), including phosphorylation, ubiquitination, nitration, and sumoylation, are vitally important in the PA pathogenesis. The large-scale analysis of PTMs could provide a global view of molecular mechanisms for PA. Proteoforms, which are used to define various protein structural and functional forms originated from the same gene, are the future direction of proteomics research. The global studies of different proteoforms and PTMs of hypophyseal hormones such as growth hormone (GH) and prolactin (PRL) and the proportion change of different GH proteoforms or PRL proteoforms in human pituitary tissue could provide new insights into the clinical value of pituitary hormones in PAs. Multiple quantitative proteomics methods, including mass spectrometry (MS)-based label-free and stable isotope-labeled strategies in combination with different PTM-peptide enrichment methods such as TiO2 enrichment of tryptic phosphopeptides and antibody enrichment of other PTM-peptides increase the feasibility for researchers to study PA proteomes. This article reviews the research status of PTMs and proteoforms in PAs, including the enrichment method, technical limitation, quantitative proteomics strategies, and the future perspectives, to achieve the goals of in-depth understanding its molecular pathogenesis, and discovering effective biomarkers and clinical therapeutic targets for predictive, preventive, and personalized treatment of PA patients.



中文翻译:

基于质谱的蛋白质组学分析人类垂体腺瘤的翻译后修饰和蛋白形式

垂体腺瘤(PA)是一种常见的颅内肿瘤,会影响下丘脑-垂体-靶器官轴系统,并危害人体健康。翻译后修饰(PTM),包括磷酸化,泛素化,硝化和磺酰化,在PA发病机理中至关重要。对PTM的大规模分析可以提供PA分子机制的全局视图。用来定义起源于同一基因的各种蛋白质结构和功能形式的蛋白质形式是蛋白质组学研究的未来方向。对垂体激素的不同蛋白形式和PTM的全球研究,例如生长激素(GH)和催乳激素(PRL)以及人脑垂体组织中不同GH蛋白形式或PRL蛋白形式的比例变化,可以为垂体激素在临床中的临床价值提供新的见解功率放大器。多种定量蛋白质组学方法,包括基于质谱(MS)的无标记和稳定同位素标记的策略,以及不同的PTM肽富集方法(例如TiO)2胰蛋白酶磷酸肽的富集和其他PTM肽的抗体富集为研究人员研究PA蛋白质组提供了可行性。本文综述了PTMs和蛋白形式在PAs中的研究现状,包括其富集方法,技术局限性,定量蛋白质组学策略和未来前景,以达到深入了解其分子发病机理,发现有效生物标志物和临床治疗手段的目的。 PA患者的预测性,预防性和个性化治疗的目标。

更新日期:2020-12-17
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