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 Wang; Emilie Giaime; Jie Shen; Yuan Ping Pang; Jin Jen; Jan Van Deursen; Zhenkun Lou

doi:10.1016/j.molcel.2015.08.011

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 Wang, Emilie Giaime, Jie Shen, Yuan Ping Pang, Jin JenJan Van Deursen, Zhenkun Lou

Research output: Contribution to journal › Article › peer-review

46 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.

Original language	English (US)
Pages (from-to)	21-34
Number of pages	14
Journal	Molecular Cell
Volume	60
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2015.08.011
State	Published - 2015

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1016/j.molcel.2015.08.011

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., Giaime, E., Shen, J., Pang, Y. P., ... Lou, Z. (2015). Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1. Molecular Cell, 60(1), 21-34. https://doi.org/10.1016/j.molcel.2015.08.011

Lee, SB, Kim, JJ, Nam, HJ, Gao, B, Yin, P, Qin, B, Yi, SY, Ham, H, Evans, D, Kim, SH, Zhang, J, Deng, M, Liu, T, Zhang, H, Billadeau, DD , Wang, L, Giaime, E, Shen, J, Pang, YP, Jen, J, Van Deursen, J & Lou, Z 2015, 'Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1', Molecular Cell, vol. 60, no. 1, pp. 21-34. https://doi.org/10.1016/j.molcel.2015.08.011

@article{d933eab9788b4c539039beab9f832d8c,

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.",

author = "Lee, {Seung Baek} and Kim, {Jung Jin} and Nam, {Hyun Ja} and Bowen Gao and Ping Yin and Bo Qin and Yi, {Sang Yeop} and Hyoungjun Ham and Debra Evans and Kim, {Sun Hyun} and Jun Zhang and Min Deng and Tongzheng Liu and Haoxing Zhang and Billadeau, {Daniel D.} and Liewei Wang and Emilie Giaime and Jie Shen and Pang, {Yuan Ping} and Jin Jen and {Van Deursen}, Jan and Zhenkun Lou",

note = "Funding Information: We thank all members of Dr. Lou{\textquoteright}s lab (Dr. Kuntian Luo, Dr. Jian Yuan, Dr. Huadong Pei, Dr. Yunhui Li, Dr. Fang Yuan, Dr. Wei Guo, Dr. Lei Zhang, Dr. Bin Xu, Dr. Hexin Shi, Yi-Hui Lin, Somaira Nowsheen, and Katherine Minter-Dykhouse) for their critical discussion of this work. We thank Dr. Myoung Shin Kim and Dr. Cheol Hong Park for animal experiments. We thank Dr. Richard J. Bram for use of time-lapse microscopy. We thank Dr. Kah Whye Peng and Diana L. Escobar for bioluminescence-based IVIS system and Dr. Thomas C. Smyrk for IHC analysis. H.H. and D.E. were supported by Mayo Graduate School. This work was supported by NIH grants CA130996, CA108961, and CA148940 to Z.L. and grant CA126828 to J.M.v.D). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

doi = "10.1016/j.molcel.2015.08.011",

language = "English (US)",

volume = "60",

pages = "21--34",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

T1 - Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1

AU - Lee, Seung Baek

AU - Kim, Jung Jin

AU - Nam, Hyun Ja

AU - Gao, Bowen

AU - Yin, Ping

AU - Qin, Bo

AU - Yi, Sang Yeop

AU - Ham, Hyoungjun

AU - Evans, Debra

AU - Kim, Sun Hyun

AU - Zhang, Jun

AU - Deng, Min

AU - Liu, Tongzheng

AU - Zhang, Haoxing

AU - Billadeau, Daniel D.

AU - Wang, Liewei

AU - Giaime, Emilie

AU - Shen, Jie

AU - Pang, Yuan Ping

AU - Jen, Jin

AU - Van Deursen, Jan

AU - Lou, Zhenkun

N1 - Funding Information: We thank all members of Dr. Lou’s lab (Dr. Kuntian Luo, Dr. Jian Yuan, Dr. Huadong Pei, Dr. Yunhui Li, Dr. Fang Yuan, Dr. Wei Guo, Dr. Lei Zhang, Dr. Bin Xu, Dr. Hexin Shi, Yi-Hui Lin, Somaira Nowsheen, and Katherine Minter-Dykhouse) for their critical discussion of this work. We thank Dr. Myoung Shin Kim and Dr. Cheol Hong Park for animal experiments. We thank Dr. Richard J. Bram for use of time-lapse microscopy. We thank Dr. Kah Whye Peng and Diana L. Escobar for bioluminescence-based IVIS system and Dr. Thomas C. Smyrk for IHC analysis. H.H. and D.E. were supported by Mayo Graduate School. This work was supported by NIH grants CA130996, CA108961, and CA148940 to Z.L. and grant CA126828 to J.M.v.D). Publisher Copyright: © 2015 Elsevier Inc.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84951942894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84951942894&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2015.08.011

DO - 10.1016/j.molcel.2015.08.011

M3 - Article

C2 - 26387737

AN - SCOPUS:84951942894

SN - 1097-2765

VL - 60

SP - 21

EP - 34

JO - Molecular Cell

JF - Molecular Cell

IS - 1

ER -

Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this