FUS/TLS从DNA修复到应激反应的功能：对肌萎缩侧索硬化症的影响
Functions of FUS/TLS from DNA repair to stress response: implications for ALS.
作者信息
Sama Reddy Ranjith Kumar, Ward Catherine L, Bosco Daryl A
机构信息
Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA
出版信息
ASN Neuro. 2014 Jun 1;6(4):1759091414544472. doi: 10.1177/1759091414544472.
Fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is a multifunctional DNA-/RNA-binding protein that is involved in a variety of cellular functions including transcription, protein translation, RNA splicing, and transport. FUS was initially identified as a fusion oncoprotein, and thus, the early literature focused on the role of FUS in cancer. With the recent discoveries revealing the role of FUS in neurodegenerative diseases, namely amyotrophic lateral sclerosis and frontotemporal lobar degeneration, there has been a renewed interest in elucidating the normal functions of FUS. It is not clear which, if any, endogenous functions of FUS are involved in disease pathogenesis. Here, we review what is currently known regarding the normal functions of FUS with an emphasis on DNA damage repair, RNA processing, and cellular stress response. Further, we discuss how ALS-causing mutations can potentially alter the role of FUS in these pathways, thereby contributing to disease pathogenesis.
肉瘤融合/脂肪肉瘤易位蛋白（FUS/TLS 或 FUS）是一种多功能的 DNA/RNA 结合蛋白，参与多种细胞功能，包括转录、蛋白质翻译、RNA 剪接和运输。FUS 最初被鉴定为一种融合癌蛋白，因此，早期文献主要关注 FUS 在癌症中的作用。随着最近的发现揭示了 FUS 在神经退行性疾病，即肌萎缩侧索硬化症和额颞叶变性中的作用，人们对阐明 FUS 的正常功能重新产生了兴趣。目前尚不清楚 FUS 的哪些内源性功能（如果有的话）参与了疾病的发病机制。在这里，我们综述了目前已知的关于 FUS 正常功能的知识，重点是 DNA 损伤修复、RNA 加工和细胞应激反应。此外，我们讨论了导致肌萎缩侧索硬化症的突变如何可能改变 FUS 在这些途径中的作用，从而导致疾病的发病机制。
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