Proteasome- and SCF-dependent degradation of yeast adenine deaminase upon transition from proliferation to quiescence requires a new F-box protein named Saf1p

Authors

  • Stéphanie Escusa,

    1. Institut de Biochimie et Génétique Cellulaires, CNRS/Université Bordeaux 2 UMR 5095, 33077 Bordeaux Cedex, France.
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  • Jurgi Camblong,

    1. Institut de Biochimie et Génétique Cellulaires, CNRS/Université Bordeaux 2 UMR 5095, 33077 Bordeaux Cedex, France.
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    • Present address: Department of Cell Biology, University of Geneva, Sciences III, 30 Quai E. Ansermet, 1211, Geneva 4, Switzerland.

  • Jean-Marc Galan,

    1. Institut Jacques Monod-CNRS/Universités Paris 6 and 7, 75251 Paris Cedex 05, France.
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  • Benoît Pinson,

    1. Institut de Biochimie et Génétique Cellulaires, CNRS/Université Bordeaux 2 UMR 5095, 33077 Bordeaux Cedex, France.
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  • Bertrand Daignan-Fornier

    Corresponding author
    1. Institut de Biochimie et Génétique Cellulaires, CNRS/Université Bordeaux 2 UMR 5095, 33077 Bordeaux Cedex, France.
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*E-mail B.Daignan-Fornier@ibgc.u-bordeaux2.fr; Tel. (+33) 5 56 99 90 55; Fax (+33) 5 56 99 90 59.

Summary

In response to nutrient limitation, Saccharomyces cerevisiae cells enter into a non-proliferating state termed quiescence. This transition is associated with profound changes in gene expression patterns. The adenine deaminase encoding gene AAH1 is among the most precociously and tightly downregulated gene upon entry into quiescence. We show that AAH1 downregulation is not specifically due to glucose exhaustion but is a more general response to nutrient limitation. We also found that Aah1p level is tightly correlated to RAS activity indicating thus an important role for the protein kinase A pathway in this regulation process. We have isolated three deletion mutants, srb10, srb11 and saf1 (ybr280c) affecting AAH1 expression during post-diauxic growth and in early stationary phase. We show that the Srb10p cyclin-dependent kinase and its cyclin, Srb11p, regulate AAH1 expression at the transcriptional level. By contrast, Saf1p, a previously uncharacterized F-box protein, acts at a post-transcriptional level by promoting degradation of Aah1p. This post-transcriptional regulation is abolished by mutations affecting the proteasome or constant subunits of the SCF (Skp1–Cullin–F-box) complex. We propose that Saf1p targets Aah1p for proteasome-dependent degradation upon entry into quiescence. This work provides the first direct evidence for active degradation of proteins in quiescent yeast cells.

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