Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1

Seung Baek Lee, Jung Jin Kim, Hyun Ja Nam, Bowen Gao, Ping Yin, Bo Qin, Sang Yeop Yi, Hyoungjun Ham, Debra Evans, Sun Hyun Kim, Jun Zhang, Min Deng, Tongzheng Liu, Haoxing Zhang, Daniel D Billadeau, Liewei M Wang, Emilie Giaime, Jie Shen, Yuan-Ping Pang, Jin JenJan Van Deursen, Zhenkun Lou

Research output: Contribution to journalArticle

30 Scopus citations

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. Lee etal. show that Parkin interacts with the anaphase promoting complex/cyclosome (APC/C) coactivators Cdc20 and Cdh1 to mediate the degradation of several key mitotic regulators independent of APC/C. Parkin deficiency results in overexpression of its substrates, mitotic defects, genomic instability, and tumorigenesis.

Original languageEnglish (US)
JournalMolecular Cell
DOIs
StateAccepted/In press - Feb 19 2015

    Fingerprint

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Lee, S. B., Kim, J. J., Nam, H. J., Gao, B., Yin, P., Qin, B., Yi, S. Y., Ham, H., Evans, D., Kim, S. H., Zhang, J., Deng, M., Liu, T., Zhang, H., Billadeau, D. D., Wang, L. M., Giaime, E., Shen, J., Pang, Y-P., ... Lou, Z. (Accepted/In press). Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1. Molecular Cell. https://doi.org/10.1016/j.molcel.2015.08.011