The YTA7 gene is involved in the regulation of the isoprenoid pathway in the yeast Saccharomyces cerevisiae

Authors

  • Klaudia Kuranda,

    1. Université de Toulouse, INSA, UPS, INP, Toulouse, France
    2. INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, France
    3. CNRS, UMR5504, Toulouse, France
    4. Institute of Biochemistry and Biophysics, PAS, Warsaw, Poland
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  • Kariona Grabinska,

    1. Institute of Biochemistry and Biophysics, PAS, Warsaw, Poland
    2. Université de Poitiers, CNRS, FRE3091, PhyMoTS, France; and
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  • Thierry Berges,

    1. Université de Poitiers, CNRS, FRE3091, PhyMoTS, France; and
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  • Francis Karst,

    1. Université de Strasbourg 1, INRA, UMR1131, Colmar, France
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  • Veronique Leberre,

    1. Université de Toulouse, INSA, UPS, INP, Toulouse, France
    2. INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, France
    3. CNRS, UMR5504, Toulouse, France
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  • Serguei Sokol,

    1. Université de Toulouse, INSA, UPS, INP, Toulouse, France
    2. INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, France
    3. CNRS, UMR5504, Toulouse, France
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  • Jean François,

    1. Université de Toulouse, INSA, UPS, INP, Toulouse, France
    2. INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, France
    3. CNRS, UMR5504, Toulouse, France
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  • Grazyna Palamarczyk

    1. Institute of Biochemistry and Biophysics, PAS, Warsaw, Poland
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  • Editor: Guenther Daum

Correspondence: Grazyna Palamarczyk, Institute of Biochemistry and Biophysics, PAS, Pawinskiego str. 5a, 02-106 Warsaw, Poland. Tel.: +48 226 584 702; fax: +48 226 584 636; e-mail: gp@ibb.waw.pl

Abstract

The isoprenoid pathway in yeasts is important not only for sterol biosynthesis but also for the production of nonsterol molecules, deriving from farnesyl diphosphate (FPP), implicated in N-glycosylation and biosynthesis of heme and ubiquinones. FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). In order to investigate the regulation of Erg20p in Saccharomyces cerevisiae, we searched for its protein partners using a two-hybrid screen, and identified five interacting proteins, among them Yta7p. Subsequently, we showed that Yta7p was a membrane-associated protein localized both to the nucleus and to the endoplasmic reticulum. Deletion of YTA7 affected the enzymatic activity of cis-prenyltransferase (the enzyme that utilizes FPP for dolichol biosynthesis) and the cellular levels of isoprenoid compounds. Additionally, it rendered cells hypersensitive to lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) that acts upstream of FPP synthase in the isoprenoid pathway. While HMGR is encoded by two genes, HMG1 and HMG2, only HMG2 overexpression was able to restore growth of the yta7Δ cells in the presence of lovastatin. Moreover, the expression level of the S. cerevisiae YTA7 gene was altered upon impairment of the isoprenoid pathway not only by lovastatin but also by zaragozic acid, an inhibitor of squalene synthase. Altogether, these results provide substantial evidence of Yta7p involvement in the regulation of isoprenoid biosynthesis.

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