Uncovering SUMOylation Dynamics during Cell-Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein

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• 作者：Joost Schimmel¹ ; ⁴ ; Karolin Eifler¹ ; ⁴ ; Jó ; n Otti Sigurð ; sson² ; ⁴ ; Sabine A.G. Cuijpers¹ ; Ivo A. Hendriks¹ ; Matty Verlaan-de Vries¹ ; Christian D. Kelstrup² ; Chiara Francavilla² ; René ; H. Medema³ ; Jesper V. Olsen² ; ^{jesper.olsen@cpr.ku.dk" class="auth_mail} ; Alfred C.O. Vertegaal¹ ; ^{vertegaal@lumc.nl" class="auth_mail}
• 刊名：Molecular Cell
• 出版年：20 March, 2014
• 年：2014
• 卷：53
• 期：6
• 页码：1053-1066
• 全文大小：2851 K

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Summary

Loss of small ubiquitin-like modification (SUMOylation) in mice causes genomic instability due to the missegregation of chromosomes. Currently, little is known about the identity of relevant SUMO target proteins that are involved in this process and about global SUMOylation dynamics during cell-cycle progression. We performed a large-scale quantitative proteomics screen to address this and identified 593 proteins to be SUMO-2 modified, including the Forkhead box transcription factor M1 (FoxM1), a key regulator of cell-cycle progression聽and聽chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M phase, when FoxM1 transcriptional activity is required. We found that a聽SUMOylation-deficient FoxM1 mutant was less active compared to wild-type FoxM1, implying that SUMOylation of the protein enhances its transcriptional activity. Mechanistically, SUMOylation blocks the dimerization of FoxM1, thereby relieving FoxM1聽autorepression. Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our findings contribute to understanding the role of SUMOylation during cell-cycle progression.