Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Androstadienes / pharmacology
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Animals
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Apoptosis / drug effects
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Benzoquinones
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Calcineurin / metabolism
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Cell Cycle / drug effects
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Cyclosporine / pharmacology
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Enzyme Inhibitors / pharmacology*
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Fungi / drug effects
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Fungi / metabolism
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HSP90 Heat-Shock Proteins / drug effects
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HSP90 Heat-Shock Proteins / metabolism
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Humans
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Immunosuppressive Agents / pharmacology*
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Lactams, Macrocyclic
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Protein Biosynthesis
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Quinones / pharmacology
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Signal Transduction / drug effects*
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Sirolimus / pharmacology
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Tacrolimus / pharmacology
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Wortmannin
Substances
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Androstadienes
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Benzoquinones
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Enzyme Inhibitors
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HSP90 Heat-Shock Proteins
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Immunosuppressive Agents
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Lactams, Macrocyclic
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Quinones
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Cyclosporine
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Calcineurin
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Sirolimus
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Tacrolimus
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Wortmannin
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geldanamycin