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The CDC-14 phosphatase controls developmental cell-cycle arrest in C. elegans

Nature Cell Biology volume 6, pages 777–783 (2004)Cite this article

Abstract

Temporal control of cell division is critical for proper animal development. To identify mechanisms involved in developmental arrest of cell division, we screened for cell-cycle mutants that disrupt the reproducible pattern of somatic divisions in the nematode C. elegans. Here, we show that the cdc-14 phosphatase is required for the quiescent state of specific precursor cells. Whereas budding yeast Cdc14p is essential for mitotic exit, inactivation of C. elegans cdc-14 resulted in extra divisions in multiple lineages, with no apparent defects in mitosis or cell-fate determination. CDC-14 fused to the green fluorescent protein (GFP–CDC-14) localized dynamically and accumulated in the cytoplasm during G1 phase. Genetic interaction and transgene expression studies suggest that cdc-14 functions upstream of the cki-1 Cip/Kip inhibitor to promote accumulation of CKI-1 in the nucleus. Our data support a model in which CDC-14 promotes a hypophosphorylated and stable form of CKI-1 required for developmentally programmed cell-cycle arrest.

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Figure 1: cdc-14 mutants display extra vulval precursor cell (VPC) divisions.
Figure 2: VPCs in cdc-14 mutants are defective in cell-cycle arrest, but not in cell-fate determination.
Figure 3: Molecular characterization of C. elegans cdc-14.
Figure 4: cdc-14 functions to inhibit G1 progression upstream of cki-1 Cip/Kip.

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Acknowledgements

We thank N. Dyson, A. Hart, I. The, P. Ernst and D.G. Srinivasan for critical reading of the manuscript. We are grateful to the Caenorhabditis Genetics Center (National Institutes of Health, National Center for Research Resources), V. Ambros, A. Fire, I. Greenwald, U. Gruneberg, S. Kim, Y. Kohara and J. Schumacher for strains and reagents. This research was supported by grants from the National Institutes of Health to S.v.d.H. R.M.S. was supported by grants from the American Cancer Society and the MGH Fund for Medical Discovery.

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  1. Massachusetts General Hospital Cancer Center and Harvard Medical School, Building 149, 13th Street, Charlestown, 02129, Massachusetts, USA

    R. Mako Saito, Audrey Perreault, Bethan Peach, John S. Satterlee & Sander van den Heuvel

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Correspondence to Sander van den Heuvel.

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Saito, R., Perreault, A., Peach, B. et al. The CDC-14 phosphatase controls developmental cell-cycle arrest in C. elegans. Nat Cell Biol 6, 777–783 (2004). https://doi.org/10.1038/ncb1154

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