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肿瘤抑制因子WWOX在正常细胞和癌细胞中的多效性功能

Pleiotropic Functions of Tumor Suppressor WWOX in Normal and Cancer Cells.

作者信息

Abu-Remaileh Muhannad, Joy-Dodson Emma, Schueler-Furman Ora, Aqeilan Rami I

机构信息

From the Departments of Immunology & Cancer Research and.

Microbiology & Molecular Genetics, Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel 91120.

出版信息

J Biol Chem. 2015 Dec 25;290(52):30728-35. doi: 10.1074/jbc.R115.676346. Epub 2015 Oct 23.

Abstract

WW domain-containing oxidoreductase (WWOX), originally marked as a likely tumor suppressor gene, has over the years become recognized for its role in a much wider range of cellular activities. Phenotypic effects displayed in animal studies, along with resolution of WWOX's architecture, fold, and binding partners, point to the protein's multifaceted biological functions. Results from a series of complementary experiments seem to indicate WWOX's involvement in metabolic regulation. More recently, clinical studies involving cases of severe encephalopathy suggest that WWOX also plays a part in controlling CNS development, further expanding our understanding of the breadth and complexity of WWOX behavior. Here we present a short overview of the various approaches taken to study this dynamic gene, emphasizing the most recent findings regarding WWOX's metabolic- and CNS-associated functions and their underlying molecular basis.

摘要

含WW结构域氧化还原酶(WWOX)最初被视为一种潜在的肿瘤抑制基因,多年来,人们逐渐认识到它在更广泛的细胞活动中发挥作用。动物研究中显示的表型效应,以及对WWOX结构、折叠和结合伙伴的解析,都指向了该蛋白多方面的生物学功能。一系列互补实验的结果似乎表明WWOX参与代谢调节。最近,涉及严重脑病病例的临床研究表明,WWOX在控制中枢神经系统发育中也发挥作用,这进一步拓展了我们对WWOX行为广度和复杂性的理解。在此,我们简要概述研究这个动态基因所采用的各种方法,重点介绍关于WWOX与代谢及中枢神经系统相关功能及其潜在分子基础的最新发现。

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WWOX guards genome stability by activating ATM.WWOX通过激活ATM来保护基因组稳定性。
Mol Cell Oncol. 2015 Feb 23;2(4):e1008288. doi: 10.1080/23723556.2015.1008288. eCollection 2015 Oct-Dec.
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WWOX loss activates aerobic glycolysis.WWOX缺失激活有氧糖酵解。
Mol Cell Oncol. 2014 Oct 30;2(2):e965640. doi: 10.4161/23723548.2014.965640. eCollection 2015 Apr-Jun.
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Tumor suppressor WWOX moderates the mitochondrial respiratory complex.肿瘤抑制因子WWOX调节线粒体呼吸复合体。
Genes Chromosomes Cancer. 2015 Dec;54(12):745-61. doi: 10.1002/gcc.22286. Epub 2015 Sep 22.
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Versatile communication strategies among tandem WW domain repeats.串联WW结构域重复序列间的通用通信策略。
Exp Biol Med (Maywood). 2015 Mar;240(3):351-60. doi: 10.1177/1535370214566558. Epub 2015 Feb 20.
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Increasing the structural coverage of tuberculosis drug targets.增加结核病药物靶点的结构覆盖范围。
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