• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Small-molecule inhibitors of the AAA+ ATPase motor cytoplasmic dynein
【24h】

Small-molecule inhibitors of the AAA+ ATPase motor cytoplasmic dynein

机译：AAA + ATPase运动胞质动力蛋白的小分子抑制剂

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The conversion of chemical energy into mechanical force by AAA+ (ATPases associated with diverse cellular activities) ATPases is integral to cellular processes, including DNA replication, protein unfolding, cargo transport and membrane fusion. The AAA+ ATPase motor cytoplasmic dynein regulates ciliary trafficking, mitotic spindle formation and organelle transport, and dissecting its precise functions has been challenging because of its rapid timescale of action and the lack of cell-permeable, chemical modulators. Here we describe the discovery of ciliobrevins, the first specific small-molecule antagonists of cytoplasmic dynein. Ciliobrevins perturb protein trafficking within the primary cilium, leading to their malformation and Hedgehog signalling blockade. Ciliobrevins also prevent spindle pole focusing, kinetochore-microtubule attachment, melanosome aggregation and peroxisome motility in cultured cells. We further demonstrate the ability of ciliobrevins to block dynein-dependent microtubule gliding and ATPase activity in vitro. Ciliobrevins therefore will be useful reagents for studying cellular processes that require this microtubule motor and may guide the development of additional AAA+ ATPase superfamily inhibitors.
机译：通过AAA +（与多种细胞活动相关的ATPase）将化学能转化为机械力ATPase是细胞过程不可或缺的部分，包括DNA复制，蛋白质展开，货物运输和膜融合。 AAA + ATPase运动的细胞质动力蛋白调节纤毛的运输，有丝分裂纺锤体的形成和细胞器的运输，解剖其精确功能一直是一项挑战，因为它的作用时间很快且缺乏可渗透细胞的化学调节剂。在这里，我们描述了ciliobrevins的发现，ciliobrevins是细胞质动力蛋白的第一个特定小分子拮抗剂。 Ciliobrevins干扰了初级纤毛内的蛋白质运输，导致其畸形和刺猬信号传导受到阻碍。 Ciliobrevins还可以防止培养细胞中的纺锤体极聚焦，动线体-微管附着，黑素体聚集和过氧化物酶体运动。我们进一步证明了ciliobrevins在体外阻断动力蛋白依赖性微管滑动和ATPase活性的能力。因此，Cioliobrevins将是用于研究需要这种微管马达的细胞过程的有用试剂，并且可以指导其他AAA + ATPase超家族抑制剂的开发。

著录项

  • 来源
    《Nature》 |2012年第7392期|p.125-129|共5页
  • 作者

    Ari J. Firestone; Joshua S. Weinger; Maria Maldonado; Kari Barlan; Lance D. Langston; Michael ODonnell; Vladimir I. Gelfand; Tarun M. Kapoor; James K. Chen;

  • 作者单位

    Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA;

    Laboratory of Chemistry and Cell Biology, Rockefeller University, New York City,New York 10021, USA;

    Laboratory of Chemistry and Cell Biology, Rockefeller University, New York City,New York 10021, USA;

    Department of Cell and Molecular Biology, Northwestern University School of Medicine, Chicago, Illinois 60611, USA;

    Laboratory of Chemistry and Cell Biology, Rockefeller University, New York City,New York 10021, USA;

    Laboratory of Chemistry and Cell Biology, Rockefeller University, New York City,New York 10021, USA;

    Department of Cell and Molecular Biology, Northwestern University School of Medicine, Chicago, Illinois 60611, USA;

    Laboratory of Chemistry and Cell Biology, Rockefeller University, New York City,New York 10021, USA;

    Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号