The cellular target specificity of pateamine A.
The natural product pateamine A (pateamine) from the sponge Mycale hentscheli is active against a wide range of dividing cells and has been shown to inhibit the functions of the eukaryotic initiation factor 4A (eIF4A). We have identified that pateamine is additionally able to modulate the formation of actin filaments and microtubules in vitro but at higher concentrations than required for inhibition of eIF4A. Cell cycle analysis confirmed that actin and tubulin are not major mediators of the cellular activity of pateamine. The range of targets identified demonstrates the value of multiple approaches to determining the mode of action of biologically active compounds.
Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
James H
JH
Matthews
Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
David R
DR
Maass
Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
Peter T
PT
Northcote
Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
Paul H
PH
Atkinson
Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
Paul H
PH
Teesdale-Spittle
D001704:Biopolymers / Q000378:metabolism; D045744:Cell Line, Tumor; D004852:Epoxy Compounds / Q000378:metabolism*; D006801:Humans; D018942:Macrolides / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism*
D001704:Biopolymers; D004852:Epoxy Compounds; D018942:Macrolides; D013844:Thiazoles; C421324:pateamine A