7-aminocholesterol has been described as being a strong inhibitor of yeast and of Gram+-bacteria proliferation. In order to determine the precise molecular target of the toxicity of this compound, we searched for yeast resistance linked to gene over-expression. We named the new yeast gene that was isolated RTA1 (EMBL X84736). This gene led to strong resistance to the inhibitor. Gene sequencing revealed that RTA1 is adjacent to the NAB1 gene which is orientated in an opposite direction and localized on chromosome VII. The RTA1 gene, which encodes a putative protein with seven potential membrane-spanning segments, was shown to be a non-essential gene in yeast.
Certain exogenously-supplied sterols, like ergost-8-enol, are efficiently converted into ergosterol in yeast. We have taken advantage of this property to study the regulation of the v v8-v v7-sterol isomerase-encoding ERG2 gene in an ergosterol auxotrophic mutant devoid of squalene-synthase activity. Ergosterol starvation leads to an 8^16-fold increase in ERG2 gene expression. Such an increase was also observed in wild-type cells either grown anaerobically or treated with SR31747A a sterol isomerase inhibitor. Exogenously-supplied zymosterol is entirely transformed into ergosterol, which represses ERG2 transcription. By contrast, exogenously-supplied ergosterol has little or no effect on ERG2 transcription.z 2000 Federation of European Biochemical Societies.
Among a series of aminocholesterol derivatives synthesized, 7-aminocholesterol is the strongest inhibitor of yeast cell growth. Using sterol auxotrophic mutant strains, we showed that this compound inhibits cell proliferation by interfering with ergosterol biosynthesis. The sterol pattern of treated cells revealed that 7-aminocholesterol inhibits delta 8-->delta 7-sterol isomerase and delta 14-sterol reductase as morpholine inhibitors. However, the novel feature of this compound is a strong cytotoxicity to yeast.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.