| Importazole, a small molecule inhibitor of the transport receptor importin-β | |
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MedLine Citation:
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PMID: 21469738 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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During interphase, the transport receptor importin-β carries cargoes into the nucleus, where RanGTP releases them. A similar mechanism operates in mitosis to generate a gradient of active spindle assembly factors around mitotic chromosomes. Importin-β and RanGTP have been implicated in additional cellular processes, but the precise roles of the Ran/importin-β pathway throughout the cell cycle remain poorly understood. We implemented a FRET-based, high-throughput small molecule screen for compounds that interfere with the interaction between RanGTP and importin-β and identified importazole, a 2,4-diaminoquinazoline. Importazole specifically blocks importin-β-mediated nuclear import both in Xenopus egg extracts and cultured cells, without disrupting transportin-mediated nuclear import or CRM1-mediated nuclear export. When added during mitosis, importazole impairs the release of an importin-β cargo FRET probe and causes both predicted and novel defects in spindle assembly. Together, these results indicate that importazole specifically inhibits the function of importin-β, likely by altering its interaction with RanGTP. Importazole is a valuable tool to evaluate the function of importin-β/RanGTP pathway at specific stages during the cell cycle. |
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Authors:
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Jonathan F Soderholm; Stephen L Bird; Petr Kalab; Yasaswini Sampathkumar; Keisuke Hasegawa; Michael Uehara-Bingen; Karsten Weis; Rebecca W Heald |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-6 |
Journal Detail:
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Title: ACS chemical biology Volume: - ISSN: 1554-8937 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101282906 Medline TA: ACS Chem Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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