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Publication : Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1.

First Author  Lee SB Year  2015
Journal  Mol Cell Volume  60
Issue  1 Pages  21-34
PubMed ID  26387737 Mgi Jnum  J:311574
Mgi Id  MGI:6771768 Doi  10.1016/j.molcel.2015.08.011
Citation  Lee SB, et al. (2015) Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1. Mol Cell 60(1):21-34
abstractText  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.
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