Uncovering SUMOylation Dynamics during Cell-Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein
| Autor: | Ivo A. Hendriks, Joost Schimmel, René H. Medema, Sabine A.G. Cuijpers, Karolin Eifler, Christian D. Kelstrup, Chiara Francavilla, Alfred C.O. Vertegaal, Jesper V. Olsen, Matty Verlaan-de Vries, Jón Otti Sigurðsson |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Genome instability
Transcription Genetic Molecular Sequence Data SUMO protein Biology Genomic Instability Chromosome segregation Chromosome Segregation Humans Amino Acid Sequence Transcription factor Mitosis Molecular Biology Regulation of gene expression Genetics Cell Cycle Forkhead Box Protein M1 Sumoylation Forkhead Transcription Factors Cell Biology Cell cycle Cell biology Gene Expression Regulation FOXM1 Small Ubiquitin-Related Modifier Proteins Protein Multimerization HeLa Cells Signal Transduction |
| Zdroj: | Molecular Cell, 53(6), 1053-1066 |
| Popis: | 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 and chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M phase, when FoxM1 transcriptional activity is required. We found that a 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 autorepression. Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our findings contribute to understanding the role of SUMOylation during cell-cycle progression. |
| Databáze: | OpenAIRE |
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