Signal-transduction cascades as targets for therapeutic intervention by natural products.
Many bacteria and fungi produce natural products that are toxic to other microorganisms and have a variety of physiological effects in animals. Recent studies have revealed that, in several cases, the targets of these agents are components of conserved signal-transduction cascades. This article looks at the mechanisms of action of five natural products--the immunosuppressants cyclosporin A, FK506 and rapamycin, and the antiproliferative agents wortmannin and geldanamycin. These mechanisms reveal the importance of signal-transduction cascades as targets for therapeutic intervention and the enormous utility of studies of natural-product action in simple model genetic systems.
Cardenas
M E
ME
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Sanfridson
A
A
Cutler
N S
NS
Heitman
J
J
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones; D019703:Calcineurin / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005658:Fungi / Q000187:drug effects / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D014176:Protein Biosynthesis; D011809:Quinones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D007166:Immunosuppressive Agents; D047029:Lactams, Macrocyclic; D011809:Quinones; D016572:Cyclosporine; D019703:Calcineurin; D020123:Sirolimus; D016559:Tacrolimus; D000077191:Wortmannin; C001277:geldanamycin