| Literature DB >> 26387737 |
Seung Baek Lee1, Jung Jin Kim1, Hyun-Ja Nam2, Bowen Gao1, Ping Yin1, Bo Qin1, Sang-Yeop Yi3, Hyoungjun Ham4,5, Debra Evans1,5,6, Sun-Hyun Kim7, Jun Zhang8, Min Deng1, Tongzheng Liu1, Haoxing Zhang1, Daniel D Billadeau4,9, Liewei Wang10, Emilie Giaime11, Jie Shen11, Yuan-Ping Pang10, Jin Jen12, Jan M van Deursen2,6, Zhenkun Lou1.
Abstract
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.Entities:
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Year: 2015 PMID： 26387737 PMCID： PMC4592523 DOI： 10.1016/j.molcel.2015.08.011
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970