Parkin Regulates Mitosis and Genomic Stability Through Cdc20/Cdh1
The neuroprotective role of Parkin is linked to its role in mitophagy and removal of toxic substrates. In some studies, Parkin has also been identified as a candidate tumor suppressor in a wide variety of human cancers. 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.
Mayo Clinic researchers, first author SeungBaek Lee, Ph.D., conducted a study to understand the role of Parkin in mitosis. The study was published in the Molecular Cell journal.
The study demonstrated how Parkin interacts with anaphase promoting complex/cyclosome (APC/C) coactivators Cdc20 andCdh1 to mediate the degradation of several key mitotic regulators independent of APC/C. 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.