The CDC-14 phosphatase controls developmental cell-cycle arrest in C. elegans.
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.
Saito
R Mako
RM
Massachusetts General Hospital Cancer Center and Harvard Medical School, Building 149, 13th Street, Charlestown, Massachusetts 02129, USA.
Perreault
Audrey
A
Peach
Bethan
B
Satterlee
John S
JS
van den Heuvel
Sander
S
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D019070:Cell Lineage; D018388:Codon, Terminator; D003593:Cytoplasm / Q000737:chemistry; D005091:Exons; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006358:Hot Temperature; D008164:Luminescent Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017384:Sequence Deletion
D029742:Caenorhabditis elegans Proteins; D018388:Codon, Terminator; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D010749:Phosphoprotein Phosphatases