Research Papers:

Reversible regulation of ORC2 SUMOylation by PIAS4 and SENP2

Ronghua Wang, Fangming Liu, Yongxu Zhao, Dan Wu, Lihan Chen, Edward T.H. Yeh _ and Chao Huang

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Oncotarget. 2017; 8:70142-70155. https://doi.org/10.18632/oncotarget.19594

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Ronghua Wang1,*, Fangming Liu1,*, Yongxu Zhao2,*, Dan Wu1, Lihan Chen2, Edward T.H. Yeh3 and Chao Huang1

1The Central Lab at Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

2Institute of Health Sciences, Chinese Academy of Sciences-Jiaotong University School of Medicine, Shanghai, China

3Department of Internal Medicine, The University of Missouri, Columbia, MO, USA

*These authors have contributed equally to this work

Correspondence to:

Edward T.H. Yeh, email: [email protected]

Chao Huang, email: [email protected]

Keywords: ORC2, SUMOylation, PIAS4, SENP2, polyploidy

Received: February 20, 2017     Accepted: June 20, 2017     Published: July 26, 2017


The small ubiquitin-related modifier (SUMO) system is essential for smooth progression of cell cycle at the G2/M phase. Many centromeric proteins are reversibly SUMOylated to ensure proper chromosome segregation at the mitosis. SUMOylation of centromeric Origin Recognition Complex subunit 2 (ORC2) at the G2/M phase is essential in maintaining genome integrity. However, how ORC2 SUMOylation is regulated remains largely unclear. Here we show that ORC2 SUMOylation is reversibly controlled by SUMO E3 ligase PIAS4 and De-SUMOylase SENP2. Either depletion of PIAS4 or overexpression of SENP2 eliminated SUMOylation of ORC2 at the G/M phase and consequently resulted in abnormal centromeric histone H3 lysine 4 methylation. Cells stably expressing SENP2 protein or small interfering RNA for PIAS4 bypassed mitosis and endoreduplicated their genome to become polyploidy. Furthermore, percentage of polyploid cells is reduced after coexpression of ORC2-SUMO2 fusion protein. Thus, the proper regulation of ORC2 SUMOylation at the G2/M phase by PIAS4 and SENP2 is critical for smooth progression of the mitotic cycle of cells.

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