Abstract #61

Proteasome- and SCF-dependent degradation of yeast adenine deaminase upon transition from proliferation to quiescence requires a new F-box protein named Saf1p. Stephanie Escusa, Damien Laporte, Jurgi Camblong, Benoit Pinson, Bertrand Daignan-Fornier. Inst Biochem & Genetique Cell, CNRS UMR 5095, Bordeaux, France.
   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 AAH1is among the most precociously and tightly down-regulated gene upon entry into quiescence. We show that AAH1down regulation 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 proteine kinase A pathway in this regulation process. We have isolated three deletion mutants, srb10, srb11and saf1(ybr280c) affecting AAH1expression during post-diauxic growth and in early stationary phase. We show that the Srb10p cyclin-dependent kinase and its cyclin, Srb11p, regulate AAH1expression 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. Several mutations in AAH1and SAF1have been isolated and their effect on protein-protein interaction is under study. In parallel, we are currently investigating the molecular signal leading to Aah1p degradation and we are trying to identify other protein targets for Saf1p-dependent degradation.

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