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Stimulation of Mammalian Translation Initiation Factor eIF4A Activity by a Small Molecule Inhibitor of Eukaryotic Translation
by
Lindqvist, Lisa
, Bordeleau, Marie-Eve
, Pelletier, Jerry
, Teesdale-Spittle, Paul
, Housman, David E.
, Novac, Olivia
, Sonenberg, Nahum
, Jankowsky, Eckhard
, Matthews, James
, Wojnar, Joanna M.
, Northcote, Peter
in
Adenosine triphosphatases
/ Amino acids
/ Animals
/ Biological Sciences
/ Chromatography, Agarose
/ Crosslinking
/ Dose-Response Relationship, Drug
/ Enzymes
/ Epoxy Compounds - chemistry
/ Epoxy Compounds - metabolism
/ Epoxy Compounds - pharmacology
/ Escherichia coli
/ Eukaryotes
/ Eukaryotic Initiation Factor-4A - metabolism
/ Gels
/ HeLa cells
/ Inhibitor drugs
/ Macrolides
/ Mammals
/ Messenger RNA
/ Mice
/ Molecules
/ Protein Biosynthesis - drug effects
/ Recombinant Proteins - metabolism
/ Resins
/ Ribonucleic acid
/ Ribosomes
/ Ribosomes - metabolism
/ RNA
/ RNA, Messenger - metabolism
/ Splicing
/ Thiazoles - chemistry
/ Thiazoles - metabolism
/ Thiazoles - pharmacology
2005
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Stimulation of Mammalian Translation Initiation Factor eIF4A Activity by a Small Molecule Inhibitor of Eukaryotic Translation
by
Lindqvist, Lisa
, Bordeleau, Marie-Eve
, Pelletier, Jerry
, Teesdale-Spittle, Paul
, Housman, David E.
, Novac, Olivia
, Sonenberg, Nahum
, Jankowsky, Eckhard
, Matthews, James
, Wojnar, Joanna M.
, Northcote, Peter
in
Adenosine triphosphatases
/ Amino acids
/ Animals
/ Biological Sciences
/ Chromatography, Agarose
/ Crosslinking
/ Dose-Response Relationship, Drug
/ Enzymes
/ Epoxy Compounds - chemistry
/ Epoxy Compounds - metabolism
/ Epoxy Compounds - pharmacology
/ Escherichia coli
/ Eukaryotes
/ Eukaryotic Initiation Factor-4A - metabolism
/ Gels
/ HeLa cells
/ Inhibitor drugs
/ Macrolides
/ Mammals
/ Messenger RNA
/ Mice
/ Molecules
/ Protein Biosynthesis - drug effects
/ Recombinant Proteins - metabolism
/ Resins
/ Ribonucleic acid
/ Ribosomes
/ Ribosomes - metabolism
/ RNA
/ RNA, Messenger - metabolism
/ Splicing
/ Thiazoles - chemistry
/ Thiazoles - metabolism
/ Thiazoles - pharmacology
2005
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Stimulation of Mammalian Translation Initiation Factor eIF4A Activity by a Small Molecule Inhibitor of Eukaryotic Translation
by
Lindqvist, Lisa
, Bordeleau, Marie-Eve
, Pelletier, Jerry
, Teesdale-Spittle, Paul
, Housman, David E.
, Novac, Olivia
, Sonenberg, Nahum
, Jankowsky, Eckhard
, Matthews, James
, Wojnar, Joanna M.
, Northcote, Peter
in
Adenosine triphosphatases
/ Amino acids
/ Animals
/ Biological Sciences
/ Chromatography, Agarose
/ Crosslinking
/ Dose-Response Relationship, Drug
/ Enzymes
/ Epoxy Compounds - chemistry
/ Epoxy Compounds - metabolism
/ Epoxy Compounds - pharmacology
/ Escherichia coli
/ Eukaryotes
/ Eukaryotic Initiation Factor-4A - metabolism
/ Gels
/ HeLa cells
/ Inhibitor drugs
/ Macrolides
/ Mammals
/ Messenger RNA
/ Mice
/ Molecules
/ Protein Biosynthesis - drug effects
/ Recombinant Proteins - metabolism
/ Resins
/ Ribonucleic acid
/ Ribosomes
/ Ribosomes - metabolism
/ RNA
/ RNA, Messenger - metabolism
/ Splicing
/ Thiazoles - chemistry
/ Thiazoles - metabolism
/ Thiazoles - pharmacology
2005
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Stimulation of Mammalian Translation Initiation Factor eIF4A Activity by a Small Molecule Inhibitor of Eukaryotic Translation
Journal Article
Stimulation of Mammalian Translation Initiation Factor eIF4A Activity by a Small Molecule Inhibitor of Eukaryotic Translation
2005
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Overview
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.
Publisher
National Academy of Sciences,National Acad Sciences
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