title: Control of Cdc14 activity coordinates cell cycle and development in Caenorhabditis elegans.
abstract: Much of our understanding of the function and regulation of the Cdc14 family of dual-specificity phosphatases originates from studies in yeasts. In these unicellular organisms Cdc14 is an important regulator of M-phase events. In contrast, the Caenorhabditis elegans homolog, cdc-14, is not necessary for mitosis, rather it is crucial for G(1)/S regulation to establish developmental cell-cycle quiescence. Despite the importance of integrating cdc-14 regulation with development, the mechanisms by which this coordination occurs are largely unknown. Here, we demonstrate that several processes conspire to focus the activity of cdc-14. First, the cdc-14 locus can produce at least six protein variants through alternative splicing. We find that a single form, CDC-14C, is the key variant acting during vulva development. Second, CDC-14C expression is limited to a subset of cells, including vulva precursors, through post-transcriptional regulation. Lastly, the CDC-14C subcellular location, and thus its potential interactions with other regulatory proteins, is regulated by nucleocytoplasmic shuttling. We find that the active export of CDC-14C from the nucleus during interphase is dependent on members of the Cyclin D and Crm1 families. We propose that these mechanisms collaborate to restrict the activity of cdc-14 as central components of an evolutionarily conserved regulatory network to coordinate cell-cycle progression with development.
authors: Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA.
authors: Sarah H
authors: SH
authors: Roy
authors: Joseph E
authors: JE
authors: Clayton
authors: Jenna
authors: J
authors: Holmen
authors: Eleanor
authors: E
authors: Beltz
authors: R Mako
authors: RM
authors: Saito
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics*; D000818:Animals; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D056741:Cyclin D / Q000378:metabolism; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D028884:Karyopherins / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014018:Tissue Distribution; D014844:Vulva / Q000166:cytology / Q000254:growth & development*; D000097606:Exportin 1 Protein
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D056741:Cyclin D; D028884:Karyopherins; D010749:Phosphoprotein Phosphatases; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C489137:cdc-14 protein, C elegans