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关于微管蛋白和精氨酸甲基转移酶家族的调查为胚胎作为抗增殖药物开发的模型系统提供了启示。

A Survey on Tubulin and Arginine Methyltransferase Families Sheds Light on Embryo as Model System for Antiproliferative Drug Development.

机构信息

Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, Ed. 16, Palermo, 90128 Sicily, Italy..

National Research Council-Istituto per lo studio degli impatti Antropici e Sostenibilità in ambiente marino (IAS-CNR), Laboratory of Molecular Ecology and Biotechnology, Detached Unit of Capo Granitola, Via del mare, Torretta Granitola (TP), 91021 Sicily, Italy.

出版信息

Int J Mol Sci. 2019 Apr 30;20(9):2136. doi: 10.3390/ijms20092136.

Abstract

Tubulins and microtubules (MTs) represent targets for taxane-based chemotherapy. To date, several lines of evidence suggest that effectiveness of compounds binding tubulin often relies on different post-translational modifications on tubulins. Among them, methylation was recently associated to drug resistance mechanisms impairing taxanes binding. The sea urchin is recognized as a research model in several fields including fertilization, embryo development and toxicology. To date, some α- and β-tubulin genes have been identified in , while no data are available in echinoderms for arginine methyl transferases (PRMT). To evaluate the exploiting of the sea urchin embryo in the field of antiproliferative drug development, we carried out a survey of the expressed α- and β-tubulin gene sets, together with a comprehensive analysis of the PRMT gene family and of the methylable arginine residues in tubulins. Because of their specificities, the sea urchin embryo may represent an interesting tool for dissecting mechanisms of tubulin targeting drug action. Therefore, results herein reported provide evidences supporting the embryo as animal system for testing antiproliferative drugs.

摘要

微管蛋白和微管 (MT) 是紫杉烷类化疗药物的作用靶点。迄今为止,有几条证据表明,结合微管蛋白的化合物的有效性通常依赖于微管蛋白上不同的翻译后修饰。其中,最近甲基化与药物耐药机制有关,这些机制会损害紫杉烷类药物的结合。海胆在受精、胚胎发育和毒理学等多个领域被认为是一种研究模式。迄今为止,已在 中鉴定出一些 α-和 β-微管蛋白基因,但在棘皮动物中尚无精氨酸甲基转移酶 (PRMT) 的相关数据。为了评估海胆胚胎在抗增殖药物开发领域的应用,我们对表达的 α-和 β-微管蛋白基因簇进行了调查,同时对 PRMT 基因家族和 微管蛋白中可甲基化的精氨酸残基进行了全面分析。由于其特异性,海胆胚胎可能是解析微管蛋白靶向药物作用机制的一个有趣工具。因此,本文提供的结果为海胆胚胎作为测试抗增殖药物的动物系统提供了证据支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e9/6539552/085f03abcf64/ijms-20-02136-g001.jpg

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