ISSN:
1617-4623
Keywords:
Aureobasidin A
;
Drug-resistant mutant
;
Target protein
;
Microtubule
;
Yeast
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
Notes:
Abstract Aureobasidin A (AbA), a cyclic depsipeptide produced byAureobasidium pullulans R106, is highly toxic to fungi includingSaccharomyces cerevisiae. We isolated several dominant mutants ofS. cerevisiae which are resistant to more than 25 µg/ml of AbA. From a genomic library of one suchAUR1 mutant, theAUR1 R (foraureobasidinresistant) mutant gene was isolated as a gene that confers resistance to AbA on wild-type cells. Its nucleotide sequence showed that the predicted polypeptide is a hydrophobic protein composed of 401 amino acids, which contains several possible transmembrane domains and at least one predicted N-linked glycosylation site. Comparison of the mutant gene with the wild-typeaur1 + gene revealed that the substitution of Phe at position 158 by Tyr is responsible for acquisition of AbA resistance. We suggest that the gene product of the wild-typeaur1 + is a target for AbA on the basis of following results. Firstly, cells that overexpress the wild-typeaur1 + gene become resistant to AbA, just as cells with anAUR1 R mutation do. Secondly, disruption of theaur1 + gene demonstrated that it is essential for growth. Thirdly, in the cells with a disruptedaur1 locus, pleiotropic morphological changes including disappearance of microtubules, degradation of tubulin and abnormal deposition of chitin were observed. Some of these abnormalities are also observed when wild-type cells are treated with AbA. The abnormality in microtubules suggests that the Aur1 protein is involved in microtubule organization and stabilization.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02172923
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