The Cdc20 homolog, FZY-1, and its interacting protein, IFY-1, are required for proper chromosome segregation in Caenorhabditis elegans.
Accurate chromosome segregation is achieved by a series of highly regulated processes that culminate in the metaphase-to-anaphase transition of the cell cycle. In the budding yeast Saccharomyces cerevisiae, the degradation of the securin protein Pds1 reverses the binding and inhibition of the separase protein Esp1. Esp1 cleaves Scc1. That cleavage promotes the dissociation of the cohesin complex from the chromosomes and leads the separation of sister chromatids. Proteolysis of Pds1 is regulated by the anaphase-promoting complex (APC), a large multi-subunit E3 ubiquitin ligase whose activity is regulated by Cdc20/Fizzy. We have previously shown that the Caenorhabditis elegans genes mdf-1/MAD1 and mdf-2/MAD2 encode key members of the spindle checkpoint. Loss of function of either gene leads to an accumulation of somatic and heritable defects and ultimately results in death. Here we show that a missense mutation in fzy-1/CDC20/Fizzy suppresses mdf-1 lethality. We identified a FZY-1-interacting protein, IFY-1, a novel destruction-box protein. IFY-1 accumulates in one-cell-arrested emb-30/APC4 embryos and interacts with SEP-1, a C. elegans separase, suggesting that IFY-1 functions as a C. elegans securin.
Kitagawa
Risa
R
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. risa.kitagawa@stjude.org
Law
Elaine
E
Tang
Lois
L
Rose
Ann M
AM
D020816:Amino Acid Motifs; D000705:Anaphase / Q000235:genetics; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D004625:Embryo, Nonmammalian; D005786:Gene Expression Regulation; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008540:Meiosis / Q000235:genetics; D009154:Mutation; D009865:Oocytes / Q000502:physiology; D034622:RNA Interference; D064247:Separase; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D043743:Ubiquitin-Protein Ligase Complexes
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; C577505:FZY-1 protein, C elegans; C581873:IFY-1 protein, C elegans; C412839:MDF-1 protein, C elegans; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; C577988:SEP-1 protein, C elegans; D064247:Separase; D008025:Ligases