Parkin Regulates Mitosis and Genomic Stability Through Cdc20/Cdh1

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2015 Sep 22

PMID 26387737

Citations 60

Authors

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 Wang

Emilie Giaime

Jie Shen

Yuan-Ping Pang

Jin Jen

Jan M van Deursen

Zhenkun Lou

Affiliations

Soon will be listed here.

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.

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References

Wang H, Song P, Du L, Tian W, Yue W, Liu M . Parkin ubiquitinates Drp1 for proteasome-dependent degradation: implication of dysregulated mitochondrial dynamics in Parkinson disease. J Biol Chem. 2011; 286(13):11649-58. PMC: 3064217. DOI: 10.1074/jbc.M110.144238. View

Iguchi M, Kujuro Y, Okatsu K, Koyano F, Kosako H, Kimura M . Parkin-catalyzed ubiquitin-ester transfer is triggered by PINK1-dependent phosphorylation. J Biol Chem. 2013; 288(30):22019-32. PMC: 3724655. DOI: 10.1074/jbc.M113.467530. View

Xue Y, Ren J, Gao X, Jin C, Wen L, Yao X . GPS 2.0, a tool to predict kinase-specific phosphorylation sites in hierarchy. Mol Cell Proteomics. 2008; 7(9):1598-608. PMC: 2528073. DOI: 10.1074/mcp.M700574-MCP200. View

Kim H, Vassilopoulos A, Wang R, Lahusen T, Xiao Z, Xu X . SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell. 2011; 20(4):487-99. PMC: 3199577. DOI: 10.1016/j.ccr.2011.09.004. View

Nagahama H, Minamishima Y, Matsumoto M, Nakamichi I, Kitagawa K, Shirane M . Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication. EMBO J. 2000; 19(9):2069-81. PMC: 305685. DOI: 10.1093/emboj/19.9.2069. View

Winklhofer K . Parkin and mitochondrial quality control: toward assembling the puzzle. Trends Cell Biol. 2014; 24(6):332-41. DOI: 10.1016/j.tcb.2014.01.001. View

Beasley S, Hristova V, Shaw G . Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson's disease. Proc Natl Acad Sci U S A. 2007; 104(9):3095-100. PMC: 1805599. DOI: 10.1073/pnas.0610548104. View

Huang H, Shi J, Orth J, Mitchison T . Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell. 2009; 16(4):347-58. PMC: 2758291. DOI: 10.1016/j.ccr.2009.08.020. View

Picchio M, Martin E, Cesari R, Calin G, Yendamuri S, Kuroki T . Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer. Clin Cancer Res. 2004; 10(8):2720-4. DOI: 10.1158/1078-0432.ccr-03-0086. View

10.

Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S . Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet. 2000; 25(3):302-5. DOI: 10.1038/77060. View

11.

Veeriah S, Taylor B, Meng S, Fang F, Yilmaz E, Vivanco I . Somatic mutations of the Parkinson's disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat Genet. 2009; 42(1):77-82. PMC: 4002225. DOI: 10.1038/ng.491. View

12.

Yan W, Young A, Soares V, Kelley R, Benezra R, Zhuang Y . High incidence of T-cell tumors in E2A-null mice and E2A/Id1 double-knockout mice. Mol Cell Biol. 1997; 17(12):7317-27. PMC: 232588. DOI: 10.1128/MCB.17.12.7317. View

13.

Horn S, Thomenius M, Johnson E, Freel C, Wu J, Coloff J . Regulation of mitochondrial morphology by APC/CCdh1-mediated control of Drp1 stability. Mol Biol Cell. 2011; 22(8):1207-16. PMC: 3078078. DOI: 10.1091/mbc.E10-07-0567. View

14.

Acquaviva C, Herzog F, Kraft C, Pines J . The anaphase promoting complex/cyclosome is recruited to centromeres by the spindle assembly checkpoint. Nat Cell Biol. 2004; 6(9):892-8. DOI: 10.1038/ncb1167. View

15.

Yeo C, Ng F, Chai C, Tan J, Koh G, Chong Y . Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival. Cancer Res. 2012; 72(10):2543-53. DOI: 10.1158/0008-5472.CAN-11-3060. View

16.

Yamamoto A, Friedlein A, Imai Y, Takahashi R, Kahle P, Haass C . Parkin phosphorylation and modulation of its E3 ubiquitin ligase activity. J Biol Chem. 2004; 280(5):3390-9. DOI: 10.1074/jbc.M407724200. View

17.

Walden H, Martinez-Torres R . Regulation of Parkin E3 ubiquitin ligase activity. Cell Mol Life Sci. 2012; 69(18):3053-67. PMC: 11115052. DOI: 10.1007/s00018-012-0978-5. View

18.

Chung K, Zhang Y, Lim K, Tanaka Y, Huang H, Gao J . Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med. 2001; 7(10):1144-50. DOI: 10.1038/nm1001-1144. View

19.

Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S . Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998; 392(6676):605-8. DOI: 10.1038/33416. View

20.

Zhang J, Wan L, Dai X, Sun Y, Wei W . Functional characterization of Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligases in tumorigenesis. Biochim Biophys Acta. 2014; 1845(2):277-93. PMC: 3995847. DOI: 10.1016/j.bbcan.2014.02.001. View