Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1
Copyright policy )Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1
Mutations in the E3 ubiquitin ligase Parkin have been linked to familial Parkinson's disease. Parkin has also been implicated in mitosis through mechanisms that are unclear. Here we show that Parkin interacts with anaphase promoting complex/cyclosome (APC/C) coactivators Cdc20 and Cdh1 to mediate the degradation of several key mitotic regulators independent of APC/C. We demonstrate that ordered progression through mitosis is orchestrated by two distinct E3 ligases through the shared use of Cdc20 and Cdh1. Furthermore, Parkin is phosphorylated and activated by polo-like kinase 1 (Plk1) during mitosis. Parkin deficiency results in overexpression of its substrates, mitotic defects, genomic instability, and tumorigenesis. These results suggest that the Parkin-Cdc20/Cdh1 complex is an important regulator of mitosis.
- Mayo Clinic United States
- Harvard University United States
- Radboud University Nijmegen Netherlands
- International St. Mary's Hospital Korea (Republic of)
- Kwandong University Korea (Republic of)
Carcinogenesis, Cdc20 Proteins, Radboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life Sciences, Ubiquitin-Protein Ligases, Mitosis, Cell Cycle Proteins, Cell Biology, Fibroblasts, Protein Serine-Threonine Kinases, Cadherins, Embryo, Mammalian, Genomic Instability, Polo-Like Kinase 1, Gene Knockout Techniques, Mice, HEK293 Cells, Proto-Oncogene Proteins, Mutation, Animals, Humans, Phosphorylation, Molecular Biology, Cells, Cultured
Carcinogenesis, Cdc20 Proteins, Radboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life Sciences, Ubiquitin-Protein Ligases, Mitosis, Cell Cycle Proteins, Cell Biology, Fibroblasts, Protein Serine-Threonine Kinases, Cadherins, Embryo, Mammalian, Genomic Instability, Polo-Like Kinase 1, Gene Knockout Techniques, Mice, HEK293 Cells, Proto-Oncogene Proteins, Mutation, Animals, Humans, Phosphorylation, Molecular Biology, Cells, Cultured
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