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  • 标题:Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation
  • 本地全文:下载
  • 作者:Marie-Eve Bordeleau ; James Matthews ; Joanna M. Wojnar
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2005
  • 卷号:102
  • 期号:30
  • 页码:10460-10465
  • DOI:10.1073/pnas.0504249102
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:RNA helicases are the largest group of enzymes in eukaryotic RNA metabolism. The DEXD/H-box putative RNA helicases form the helicase superfamily II, whose members are defined by seven highly conserved amino acid motifs, making specific targeting of selected members a challenging pharmacological problem. The translation initiation factor eIF4A is the prototypical DEAD-box RNA helicase that works in conjunction with eIF4B and eIF4H and as a subunit of eIF4F to prepare the mRNA template for ribosome binding, possibly by unwinding the secondary structure proximal to the 5' m7GpppN cap structure. We report the identification and characterization of a small molecule inhibitor of eukaryotic translation initiation that acts in an unusual manner by stimulating eIF4A-associated activities. Our results suggest that proper control of eIF4A helicase activity is necessary for efficient ribosome binding and demonstrate the feasibility of selectively targeting DEAD-box RNA helicases with small molecules.
  • 关键词:chemical biology ; DEAD-box helicase ; pateamine
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