Characterization of staurosporine-sensitive mutants of Saccharomyces cerevisiae: vacuolar functions affect staurosporine sensitivity

被引：0

作者：

S. Yoshida

Y. Anraku

机构：

[1] Central Laboratories for Key Technology,

[2] Kirin Brewery Co. Ltd.,undefined

[3] 1-13-5,undefined

[4] Fukuura,undefined

[5] Kanazawa-ku,undefined

[6] Yokohama-shi,undefined

[7] Kanagawa 236-0004,undefined

[8] Japan E-mail: satoshiy@kirin.co.jp Tel.: +81-45-788-7360; Fax: +81-45-788-4042,undefined

[9] Department of Biosciences,undefined

[10] Teikyo University of Science and Technology,undefined

[11] Yatsusawa 2525,undefined

[12] Uenohara-machi,undefined

[13] Kitatsuru-gun,undefined

[14] Yamanashi 409-0193,undefined

[15] Japan,undefined

来源：

Molecular and General Genetics MGG | 2000年 / 263卷

关键词：

Key words Staurosporine; Vacuolar-type proton pumping ATPase; Vacuolar protein sorting; ATP-binding cassette transporter; Saccharomyces cerevisiae;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Mutations at several loci affect the sensitivity of the yeast Saccharomyces cerevisiae to staurosporine. We report here the characterization of novel staurosporine- and temperature-sensitive mutants (stt). Cloning and integration mapping showed that the genes STT2/STT6, STT5, STT7, STT8 and STT9 are allelic to VPS18, ERG10, GPI1, VPS34 and VPS11, respectively. The products of ERG10 and GPI1, respectively, catalyze mevalonate and glycosyl phosphatidylinositol anchor synthesis, while VPS18 and VPS11 genes belong to the class C VPS (Vacuolar Protein Sorting) genes, and the VPS34 gene is classified as a class D VPS. Therefore, staurosporine sensitivity is affected by ergosterol and glycolipid biosynthesis and by vacuolar functions. We found that other vps mutants belonging to classes C and D exhibit staurosporine sensitivity, and that they show calcium sensitivity and fail to grow on glycerol as the sole carbon source; both of the last two characteristics are shared by vacuolar H+-ATPase mutants (vma). As vma mutants were also found to show staurosporine-sensitive growth, staurosporine sensitivity is likely to be affected by acidification of the vacuole. Moreover, wild type yeast cells are more sensitive to staurosporine in alkaline media than in acidic media, suggesting that staurosporine is exported from the cytosol by H+/drug antiporters. Pleiotropic drug resistance (PDR) genes also provide some resistance to staurosporine, because Δpdr5, Δsnq2 and Δyor1 strains are more sensitive to staurosporine than the wild-type strain. This suggests that staurosporine is also exported by the ATP-binding cassette (ABC) transporters on the plasma membrane. vma mutants and vps mutants of classes C and D vps are sensitive to hygromycin B and vanadate, while ABC transporter-depleted mutants do not show such sensitivity, indicating that two systems differ in their ability to protect the cell against different types of drug.

引用

页码：877 / 888

页数：11