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

Nature volume 398, pages 818–823 (1999)Cite this article

Abstract

In eukaryotes, the activation of mitotic cyclin-dependent kinases (CDKs) induces mitosis, and their inactivation causes cells to leave mitosis1. In budding yeast, two redundant mechanisms induce the inactivation of mitotic CDKs. In one mechanism, a specialized ubiquitin-dependent proteolytic system (called the APC-dependent proteolysis machinery) degrades the mitotic (Clb) cyclin subunit. In the other, the kinase-inhibitor Sic1 binds to mitotic CDKs and inhibits their kinase activity1,2. The highly conserved protein phosphatase Cdc14 promotes both Clb degradation and Sic1 accumulation. Cdc14 promotes SIC1 transcription and the stabilization of Sic1 protein by dephosphorylating 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 sequestered in the nucleolus for most of the cell cycle. During nuclear division, 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 have identified a negative regulator of Cdc14, Cfi1, that anchors Cdc14 in the nucleolus.

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Figure 1: Subcellular localization of Cdc14-HA during the cell cycle.
Figure 2: Cdc14 localization in various cell cycle mutants.
Figure 3: Cfi1 interacts with Cdc14 and regulates its subcellular localization.
Figure 4: Cells lacking CFI1 are impaired in activation of mitotic kinases.
Figure 5: Overexpression of CFI1 induces high levels of Clb2-associated kinase activity and cell-cycle arrest in telophase.

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Acknowledgements

We thank V. Guacci, L. Guarente, L. Pillus, S. Bell and F. Klein for gifts of strains and antibodies; F. Lewitter for help with sequence alignments; and M. Tyers, S. Bell, T. Orr-Weaver, P. Sorger and S. Prinz for critically reading the manuscript.

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  1. Center for Cancer Research, Massachusetts Institute of Technology, Building E17, 40 Ames Street, Cambridge, 02139, Massachusetts, USA

    Rosella Visintin, Ellen S. Hwang & Angelika Amon

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Correspondence to Angelika Amon.

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Visintin, R., Hwang, E. & Amon, A. Cfi1 prevents premature exit from mitosis by anchoring Cdc14 phosphatase in the nucleolus. Nature 398, 818–823 (1999). https://doi.org/10.1038/19775

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