Cfi1 prevents premature exit from mitosis by anchoring Cdc14 phosphatase in the nucleolus

In eukaryotes, the activation of mitotic cyclin-dependent kinases (CDKs) in duces mitosis, and their inactivation causes cells to leave mitosis(1). In budding yeast, two redundant mechanisms induce the inactivation of mitotic CDKs. In one mechanism, a specialized ubiquitin-dependent proteolytic syste m (called the APC-dependent proteolysis machinery) degrades the mitotic (Cl b) cyclin subunit. In the other, the kinase-inhibitor Sic1 binds to mitotic CDKs and inhibits their kinase activity(1,2). The highly conserved protein phosphatase Cdc14 promotes both Clb degradation and Sic1 accumulation. Cdc 14 promotes SIC1 transcription and the stabilization of Sic1 protein by dep hosphorylating Sic1 and its transcription factor Swi5. Cdc14 activates the degradation of Clb cyclins by dephosphorylating the APC-specificity factor Cdh1 (refs 3, 4). So how is Cdc14 regulated? Here we show that Cdc14 is seq uestered in the nucleolus for most of the cell cycle. During nuclear divisi on, Cdc14 is released from the nucleolus, allowing it to reach its targets. A highly conserved signalling cascade, critical for the exit from mitosis, is required for this movement of Cdc14 during anaphase. Furthermore, we ha ve identified a negative regulator of Cdc14 Cfi1, that anchors Cdc14 in the nucleolus.