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磷酸化蛋白质组学分析以鉴定信号通路改变及激酶靶向癌症疗法

Phosphoproteomics Profiling to Identify Altered Signaling Pathways and Kinase-Targeted Cancer Therapies.

作者信息

Deb Barnali, George Irene A, Sharma Jyoti, Kumar Prashant

机构信息

Institute of Bioinformatics, International Technology Park, Bangalore, India.

Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India.

出版信息

Methods Mol Biol. 2020;2051:241-264. doi: 10.1007/978-1-4939-9744-2_10.

DOI:10.1007/978-1-4939-9744-2_10
PMID:31552632
Abstract

Phosphorylation is one of the most extensively studied posttranslational modifications (PTM), which regulates cellular functions like cell growth, differentiation, apoptosis, and cell signaling. Kinase families cover a wide number of oncoproteins and are strongly associated with cancer. Identification of driver kinases is an intense area of cancer research. Thus, kinases serve as the potential target to improve the efficacy of targeted therapies. Mass spectrometry-based phosphoproteomic approach has paved the way to the identification of a large number of altered phosphorylation events in proteins and signaling cascades that may lead to oncogenic processes in a cell. Alterations in signaling pathways result in the activation of oncogenic processes predominantly regulated by kinases and phosphatases. Therefore, drugs such as kinase inhibitors, which target dysregulated pathways, represent a promising area for cancer therapy.

摘要

磷酸化是研究最为广泛的翻译后修饰(PTM)之一,它调控细胞生长、分化、凋亡和细胞信号传导等细胞功能。激酶家族涵盖众多癌蛋白,且与癌症密切相关。鉴定驱动激酶是癌症研究的一个热点领域。因此,激酶可作为提高靶向治疗疗效的潜在靶点。基于质谱的磷酸化蛋白质组学方法为鉴定蛋白质和信号级联中大量可能导致细胞致癌过程的磷酸化改变事件铺平了道路。信号通路的改变导致主要由激酶和磷酸酶调控的致癌过程的激活。因此,诸如激酶抑制剂这类靶向失调通路的药物是癌症治疗的一个有前景的领域。

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Bioinformatics Analysis of Global Proteomic and Phosphoproteomic Data Sets Revealed Activation of NEK2 and AURKA in Cancers.
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