Subcellular Localization of the Cyclin Dependent Kinase Inhibitor Sic1 is Modulated by the Carbon Source in Budding Yeast

The cyclin dependent kinase inhibitor Sic1 and the cyclin Clb5 are essential regulators of the cyclindependent kinase Cdc28 during the G1 to S transition in budding yeast. Yeast enters S phase afterubiquitin-mediated degradation of Sic1, an event triggered by Cln1,2-Cdc28 mediated phosphorylation. We recently showed that Sic1 is involved in carbon source modulation of the critical cell sizerequired to enter S phase. Here we show that the amount and sub-cellular localization of Sic1 are alsocarbon source-modulated. We identify a bipartite nuclear localization sequence responsible for nuclearlocalization of Sic1 and for correct cell cycle progression in a carbon-source dependent manner.Similarly to Cip/Kip proteins ? Sic1 mammalian counterparts ? Sic1 facilitates nuclear accumulation ofits cognate cyclin, since cytoplasmic building-up of Clb5 is observed upon switching off expression ofthe SIC1 gene. Our data indicate a previously unrecognized inhibitor/activator dual role for Sic1 andput it among key molecules whose activity is regulated by their nuclear-cytoplasmic localization.