1. Academic Validation
  2. SUMOylation Promotes Nuclear Import and Stabilization of Polo-like Kinase 1 to Support Its Mitotic Function

SUMOylation Promotes Nuclear Import and Stabilization of Polo-like Kinase 1 to Support Its Mitotic Function

  • Cell Rep. 2017 Nov 21;21(8):2147-2159. doi: 10.1016/j.celrep.2017.10.085.
Donghua Wen 1 Jianguo Wu 1 Lei Wang 1 Zheng Fu 2
Affiliations

Affiliations

  • 1 Department of Human and Molecular Genetics, Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.
  • 2 Department of Human and Molecular Genetics, Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA. Electronic address: zheng.fu@vcuhealth.org.
Abstract

As a pivotal mitotic regulator, polo-like kinase 1 (PLK1) is under highly coordinated and multi-layered regulation. However, the pathways that control PLK1's activity and function have just begun to be elucidated. PLK1 has recently been shown to be functionally modulated by post-translational modifications (PTMs), including phosphorylation and ubiquitination. Herein, we report that SUMOylation plays an essential role in regulating PLK1's mitotic function. We found that Ubc9 was recruited to PLK1 upon initial phosphorylation and activation by CDK1/cyclin B. By in vivo and in vitro SUMOylation assays, PLK1 was identified as a physiologically relevant small ubiquitin-related modifier (SUMO)-targeted protein, preferentially modified by SUMO-1. We further showed that K492 on PLK1 is essential for SUMOylation. SUMOylation causes PLK1's nuclear import and significantly increases its protein stability, both of which are critical for normal mitotic progression and genomic integrity. Our findings suggest that SUMOylation is an important regulatory mechanism governing PLK1's mitotic function.

Keywords

PLK1; SUMOylation; Ubc9; genomic stability; mitotic progression; nuclear import; protein stability.

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