Abstract 4294: SUMOylation promotes nuclear import and stabilization of polo-like kinase 1 to support its mitotic function

Abstract

Abstract As a pivotal mitotic regulator, polo-like kinase 1 (PLK1) is under highly coordinated and multi-layered regulation. However, the regulatory 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 for the first time that a novel PTM, 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 SUMO-targeted protein, preferentially modified by SUMO-1. We further showed that K492 on PLK1 was the lysine residue essential for SUMOylation. SUMOylation not only led to PLK1's nuclear import, but also significantly increased its protein stability by preventing the recruitment of APC/Ccdh1, the ubiquitin E3-ligase of PLK1. Resembling Ubc9 deficiency, cells expressing PLK1-K492R mutant exhibited mitotic aberrations characterized by prolonged mitotic progression, and misaligned and/or mis-segregated chromosomes, which could be rescued by reintroducing SUMOylation modification to PLK1. Collectively, our findings suggest that SUMOylation is another important regulatory mechanism governing PLK1's mitotic function to ensure normal mitotic progression and genomic integrity. Citation Format: Donghua Wen, Jianguo Wu, Lei Wang, Zheng Fu. SUMOylation promotes nuclear import and stabilization of polo-like kinase 1 to support its mitotic function [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4294.