The cyclin dependent kinase inhibitor Sic1 and the cyclin Clb5 are essential regulators of the cyclin dependent kinase Cdc28 during the G1 to S transition in budding yeast. Yeast enters S phase after ubiquitin-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 size required to enter S phase. Here we show that the amount and sub-cellular localization of Sic1 are also carbon source-modulated. We identify a bipartite nuclear localization sequence responsible for nuclear localization 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 of its cognate cyclin, since cytoplasmic building-up of Clb5 is observed upon switching off expression of the SIC1 gene. Our data indicate a previously unrecognized inhibitor/activator dual role for Sic1 and put it among key molecules whose activity is regulated by their nuclear-cytoplasmic localization.

• PMID: 16294029
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Rossi RL, Zinzalla V, Mastriani A, Vanoni M, Alberghina L

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