1. Cyclophilin-dependent stimulation of transcription by cyclosporin A.
- Author
-
Larson TG and Nuss DL
- Subjects
- Cycloheximide pharmacology, Drug Resistance, Microbial genetics, Drug Resistance, Microbial radiation effects, Egtazic Acid analogs & derivatives, Egtazic Acid pharmacology, Genes, Fungal, Laccase, Mutagenesis, Neomycin pharmacology, Peptidylprolyl Isomerase, Promoter Regions, Genetic drug effects, RNA, Messenger metabolism, Recombinant Fusion Proteins metabolism, Ultraviolet Rays, Xylariales drug effects, Xylariales enzymology, Amino Acid Isomerases metabolism, Carrier Proteins metabolism, Cyclosporine pharmacology, Oxidoreductases genetics, Oxidoreductases metabolism, Transcription, Genetic drug effects, Xylariales genetics
- Abstract
Exposure to cyclosporin A (CspA) increased laccase (lac-1) transcript accumulation in the chestnut blight fungus Cryphonectria parasitica. This response was suppressed by compounds that interfere with calcium-dependent signal transduction and by the presence of a virulence-attenuating mycovirus. CspA stimulated the accumulation of mRNA from a nonhomologous reporter fused to the lac-1 promoter, indicating that the increased transcript levels resulted from an increase in promoter activity. Based on the current model for the regulation of lac-1 transcription, these results suggest that CspA interferes with a negative regulatory pathway that normally constrains lac-1 promoter activity. Significantly, CspA did not stimulate lac-1 transcription in mutant strains deficient in CspA binding activity, directly demonstrating a requirement for the interaction of CspA and cyclophilin in the modulation of lac-1 transcription. Our results establish that CspA treatment can stimulate gene transcription and that cyclophilin is the cellular receptor that mediates this activity.
- Published
- 1993
- Full Text
- View/download PDF