Ratjadone and leptomycin B block CRM1-dependent nuclear export by identical mechanisms

被引:69
作者
Meissner, T
Krause, E
Vinkemeier, U
机构
[1] Free Univ Berlin, Abt Zellulare Signalverarbeitung, Leibniz Forschungsinst Mol Pharmakol, D-13125 Berlin, Germany
[2] Free Univ Berlin, Arbeitsgrp Massenspektrometrie, Leibniz Forschungsinst Mol Pharmakol, D-13125 Berlin, Germany
关键词
ratjadone; leptomycin; chromosomal region maintenance 1; nuclear export;
D O I
10.1016/j.febslet.2004.08.056
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Research on the export of proteins and nucleic acids from the nucleus to the cytoplasm has greatly gained from the discovery that the actinobacterial toxin leptomycin B (LMB) specifically inactivates the export receptor chromosomal region maintenance 1 (CRM1). Recently, it was shown that myxobacterial cytotoxins, named ratjadones (RATs), also bind to CRM1 and inhibit nuclear export. However, the reaction mechanism of RATs was not resolved. Here, we show that LMB and RAT A employ the same molecular mechanism to inactivate CRM1. Alkylation of residue Cys528 of CRM1 determines both LMB and RAT sensitivity and prevents nuclear export of CRM1 cargo proteins. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:27 / 30
页数:4
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