title: Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1.
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.
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Seung Baek
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jung Jin
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Nam
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Bowen
authors.initials: B
authors.lastname: Gao
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Yin
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.affiliation: Department of Pathology, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon 404 834, Republic of Korea.
authors.forename: Sang-Yeop
authors.initials: SY
authors.lastname: Yi
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.|Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Hyoungjun
authors.initials: H
authors.lastname: Ham
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.|Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, USA.|Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Evans
authors.affiliation: Department of Family Medicine, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon 404 834, Republic of Korea.
authors.forename: Sun-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Deng
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Tongzheng
authors.initials: T
authors.lastname: Liu
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Haoxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.|Division of Oncology Research and Schulze Center for Novel Therapeutics, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Billadeau
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Liewei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Neurologic Diseases, Department of Neurology, Brigham & Women's Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Emilie
authors.initials: E
authors.lastname: Giaime
authors.affiliation: Center for Neurologic Diseases, Department of Neurology, Brigham & Women's Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Pang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Jen
authors.affiliation: Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA.|Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Deursen
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Lou
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D063646:Carcinogenesis / Q000235:genetics; D064199:Cdc20 Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D055786:Gene Knockout Techniques; D042822:Genomic Instability; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D015820:Cadherins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D044767:Ubiquitin-Protein Ligases; D000097869:Polo-Like Kinase 1; C111567:parkin protein