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异常蛋白质合成与癌症发生:经典真核起始、延伸和终止因子在肿瘤发生中的作用。

Aberrant protein synthesis and cancer development: The role of canonical eukaryotic initiation, elongation and termination factors in tumorigenesis.

机构信息

MRC Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Rd, Cambridge CB2 1QR, UK.

MRC Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Rd, Cambridge CB2 1QR, UK.

出版信息

Semin Cancer Biol. 2022 Nov;86(Pt 3):151-165. doi: 10.1016/j.semcancer.2022.04.006. Epub 2022 Apr 26.

Abstract

In tumourigenesis, oncogenes or dysregulated tumour suppressor genes alter the canonical translation machinery leading to a reprogramming of the translatome that, in turn, promotes the translation of selected mRNAs encoding proteins involved in proliferation and metastasis. It is therefore unsurprising that abnormal expression levels and activities of eukaryotic initiation factors (eIFs), elongation factors (eEFs) or termination factors (eRFs) are associated with poor outcome for patients with a wide range of cancers. In this review we discuss how RNA binding proteins (RBPs) within the canonical translation factor machinery are dysregulated in cancers and how targeting such proteins is leading to new therapeutic avenues.

摘要

在肿瘤发生过程中,癌基因或失调的肿瘤抑制基因改变了经典的翻译机制,导致翻译组的重编程,进而促进了参与增殖和转移的选定 mRNA 的翻译。因此,真核起始因子 (eIFs)、延伸因子 (eEFs) 或终止因子 (eRFs) 的异常表达水平和活性与广泛癌症患者的不良预后相关也就不足为奇了。在这篇综述中,我们讨论了经典翻译因子机制中的 RNA 结合蛋白 (RBP) 在癌症中的失调情况,以及针对这些蛋白的靶向治疗如何开辟新的治疗途径。

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