摘要
RNA结合蛋白(RBP)HuR是研究最广泛的真核后转录基因表达的调节器之一,且它在介导细胞的凋亡,增殖和生存刺激上起着重要的生理学作用。生理或压力刺激后,HuR蛋白结合腺苷酸Urydinilate丰富元素(AREs)通常包含3’UTR的转录,然后它从细胞核移动到细胞质,从而调控货物mRNAs的半衰期和/或转录。HuR的次级细胞定位和表达的混乱已经与多种疾病的生理病理相关,且这种蛋白已经被建议做为一种潜在的药物靶标。最近的调查结果也重新评估了HuR作为一种连接和聚腺苷酸化因素,扩大它的机能活动范围到预mRNAs的成熟。这篇综述,我们生成了一个关于HuR功能的综合的图谱来讨论就HuR作为药理学靶点的含义和不良或者积极影响来预期其调节作用。首先,我们关注了关于HuR在细胞核的机械作用和在长非编码RNAs的调节作用的最新发现;然后,我们描述了动物模型和临床联用以及在癌症方面的重要性;最后,我们对影响HuR的后转录控制的药理学工具和关于鉴定HuR抑制剂的尝试进行了综述。
关键词: ELAVL1,HuR,HuR催化剂,HuR动物模型,HuR成药性,HuR抑制剂,后转录控制
Current Drug Targets
Title:Targeting the Multifaceted HuR Protein, Benefits and Caveats
Volume: 16 Issue: 5
Author(s): Chiara Zucal, Vito D’Agostino, Rosa Loffredo, Barbara Mantelli, Natthakan Thongon, Preet Lal, Elisa Latorre and Alessandro Provenzani
Affiliation:
关键词: ELAVL1,HuR,HuR催化剂,HuR动物模型,HuR成药性,HuR抑制剂,后转录控制
摘要: The RNA-binding protein (RBP) HuR is one of the most widely studied regulators of the eukaryotic posttranscriptional gene expression and it plays a physiological role in mediating the cellular response to apoptotic, proliferating and survival stimuli. Following physiological or stress stimuli, HuR protein binds to Adenylate-Urydinilate rich elements (AREs) generally contained in the 3’UTR of transcripts, then it shuttles from the nucleus to the cytoplasm and regulates the half-life and/or translation of cargo mRNAs. Derangements in sub-cellular localization and expression of HuR have been associated with the pathophysiology of many diseases and this protein has been proposed as a potential drug target. Recent findings also re-evaluated HuR as a splicing and polyadenylation factor, expanding its spectrum of functional activity up to the maturation of pre-mRNAs. In this review, we generate a comprehensive picture of HuR functionality to discuss the implications of considering HuR as pharmacological target and the detrimental or positive impact that can be expected upon its modulation. Firstly, we focus on the recent findings about the mechanistic role of HuR in the nucleus and in the regulation of long non coding RNAs; then we describe the animal models and the clinical association and significance in cancer; finally, we have reviewed the pharmacological tools that influence HuR’s post-transcriptional control and the efforts made to identify specific HuR inhibitors.
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Chiara Zucal , Vito D’Agostino , Rosa Loffredo , Barbara Mantelli , Natthakan Thongon , Preet Lal , Elisa Latorre and Alessandro Provenzani , Targeting the Multifaceted HuR Protein, Benefits and Caveats, Current Drug Targets 2015; 16 (5) . https://dx.doi.org/10.2174/1389450116666150223163632
DOI https://dx.doi.org/10.2174/1389450116666150223163632 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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