马尿酸甾醇——一种强效的真核生物起始因子4A的类固醇抑制剂。
Hippuristanol - A potent steroid inhibitor of eukaryotic initiation factor 4A.
作者信息
Cencic Regina, Pelletier Jerry
机构信息
Department of Biochemistry, McGill University , Montreal, Québec, Canada.
Department of Biochemistry, McGill University, Montreal, Québec, Canada; The Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Québec, Canada; Department of Oncology, McGill University, Montreal, Québec, Canada.
出版信息
Translation (Austin). 2016 Jan 4;4(1):e1137381. doi: 10.1080/21690731.2015.1137381. eCollection 2016 Jan-Jun.
Protein synthesis and its regulatory signaling pathways play essential roles in the initiation and maintenance of the cancer phenotype. Insight obtained over the last 3 decades on the mechanisms regulating translation in normal and transformed cells have revealed that perturbed control in cancer cells may offer an Achilles' heel for the development of novel anti-neoplastic agents. Several small molecule inhibitors have been identified and characterized that target translation initiation - more specifically, the rate-limiting step where ribosomes are recruited to mRNA templates. Among these, hippuristanol, a polyhydroxysteroid from the gorgonian Isis hippuris has been found to inhibit translation initiation by blocking the activity of eukaryotic initiation factor (eIF) 4A, an essential RNA helicase involved in this process. Herein, we highlight the biological properties of this compound, its potential development as an anti-cancer agent, and its use to validate eIF4A as an anti-neoplastic target.
蛋白质合成及其调控信号通路在癌症表型的起始和维持中起着至关重要的作用。过去30年中，有关正常细胞和转化细胞中翻译调控机制的研究发现，癌细胞中翻译控制的紊乱可能为新型抗肿瘤药物的开发提供了一个薄弱环节。已鉴定并表征了几种靶向翻译起始的小分子抑制剂——更具体地说，是将核糖体招募到mRNA模板的限速步骤。其中，来自柳珊瑚Isis hippuris的多羟基类固醇马尿甾醇已被发现可通过阻断真核起始因子（eIF）4A的活性来抑制翻译起始，eIF4A是参与此过程的一种必需的RNA解旋酶。在此，我们重点介绍该化合物的生物学特性、其作为抗癌药物的潜在开发以及其用于验证eIF4A作为抗肿瘤靶点的用途。
Zotero 插件