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融合蛋白介导癌症中蛋白质相互作用网络的改变。

Fusion proteins mediate alternation of protein interaction networks in cancers.

机构信息

Cancer Genomics and BioComputing of Complex Diseases Lab, Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.

Cancer Genomics and BioComputing of Complex Diseases Lab, Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.

出版信息

Adv Protein Chem Struct Biol. 2022;131:165-176. doi: 10.1016/bs.apcsb.2022.05.007. Epub 2022 Jun 7.

Abstract

Fusions of two different genes could lead to the production of chimeric RNAs, which could be translated into novel fusion (or chimeric) proteins. Fusion proteins often act as oncoproteins and drive cancer development, particularly in leukemia and lymphomas. Fusion proteins modify the existing protein-protein interaction (PPI) networks, which could eliminate some PPIs by removing protein domains in such fusions. This alternation of protein interaction networks could impact the signaling pathways and switch on the cancer-promoting activity that could drive the generation of cancer phenotypes and/or loss of controlled apoptosis. Thus, knowledge of the fusion proteins and their protein interaction networks could facilitate a deeper molecular understanding of cancer development, which could help to design new approaches for cancer therapies. Here, we discuss the structural features of fusion proteins and how they impact the PPI networks in cancers. Further, we discuss how to analyze the fusion protein-mediated alternation of PPI networks in cancers.

摘要

两种不同基因的融合可能导致嵌合 RNA 的产生,这些 RNA 可以被翻译成新的融合(或嵌合)蛋白。融合蛋白通常作为癌蛋白发挥作用,并促进癌症的发展,特别是在白血病和淋巴瘤中。融合蛋白改变了现有的蛋白质-蛋白质相互作用(PPI)网络,通过在这些融合中去除蛋白质结构域,可以消除一些 PPI。蛋白质相互作用网络的这种改变可能会影响信号通路,并开启促进癌症的活性,从而导致癌症表型的产生和/或失去控制的细胞凋亡。因此,了解融合蛋白及其蛋白质相互作用网络可以帮助我们更深入地理解癌症的发展机制,从而有助于设计新的癌症治疗方法。在这里,我们讨论了融合蛋白的结构特征以及它们如何影响癌症中的 PPI 网络。此外,我们还讨论了如何分析癌症中融合蛋白介导的 PPI 网络的改变。

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