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DDX5和DDX17——肿瘤发生和肿瘤进展调控中的多面蛋白

DDX5 and DDX17-multifaceted proteins in the regulation of tumorigenesis and tumor progression.

作者信息

Xu Kun, Sun Shenghui, Yan Mingjing, Cui Ju, Yang Yao, Li Wenlin, Huang Xiuqing, Dou Lin, Chen Beidong, Tang Weiqing, Lan Ming, Li Jian, Shen Tao

机构信息

The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, China.

Peking University Fifth School of Clinical Medicine, Beijing, China.

出版信息

Front Oncol. 2022 Aug 3;12:943032. doi: 10.3389/fonc.2022.943032. eCollection 2022.

Abstract

DEAD-box (DDX)5 and DDX17, which belong to the DEAD-box RNA helicase family, are nuclear and cytoplasmic shuttle proteins. These proteins are expressed in most tissues and cells and participate in the regulation of normal physiological functions; their abnormal expression is closely related to tumorigenesis and tumor progression. DDX5/DDX17 participate in almost all processes of RNA metabolism, such as the alternative splicing of mRNA, biogenesis of microRNAs (miRNAs) and ribosomes, degradation of mRNA, interaction with long noncoding RNAs (lncRNAs) and coregulation of transcriptional activity. Moreover, different posttranslational modifications, such as phosphorylation, acetylation, ubiquitination, and sumoylation, endow DDX5/DDX17 with different functions in tumorigenesis and tumor progression. Indeed, DDX5 and DDX17 also interact with multiple key tumor-promoting molecules and participate in tumorigenesis and tumor progression signaling pathways. When DDX5/DDX17 expression or their posttranslational modification is dysregulated, the normal cellular signaling network collapses, leading to many pathological states, including tumorigenesis and tumor development. This review mainly discusses the molecular structure features and biological functions of DDX5/DDX17 and their effects on tumorigenesis and tumor progression, as well as their potential clinical application for tumor treatment.

摘要

属于DEAD盒RNA解旋酶家族的DEAD盒(DDX)5和DDX17是核质穿梭蛋白。这些蛋白在大多数组织和细胞中表达,并参与正常生理功能的调节;它们的异常表达与肿瘤发生和肿瘤进展密切相关。DDX5/DDX17几乎参与RNA代谢的所有过程,如mRNA的可变剪接、微小RNA(miRNA)和核糖体的生物合成、mRNA的降解、与长链非编码RNA(lncRNA)的相互作用以及转录活性的共调节。此外,不同的翻译后修饰,如磷酸化、乙酰化、泛素化和类泛素化,赋予DDX5/DDX17在肿瘤发生和肿瘤进展中不同的功能。实际上,DDX5和DDX17还与多种关键的肿瘤促进分子相互作用,并参与肿瘤发生和肿瘤进展信号通路。当DDX5/DDX17的表达或其翻译后修饰失调时,正常的细胞信号网络崩溃,导致包括肿瘤发生和肿瘤发展在内的许多病理状态。本文综述主要讨论了DDX5/DDX17的分子结构特征和生物学功能、它们对肿瘤发生和肿瘤进展的影响,以及它们在肿瘤治疗中的潜在临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25fe/9382309/b3f703bff19a/fonc-12-943032-g001.jpg

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