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

被引：152

作者：

Schimmel, Joost ^{[1
]}

Eifler, Karolin ^{[1
]}

Sigurdsson, Jon Otti ^{[2
]}

Cuijpers, Sabine A. G. ^{[1
]}

Hendriks, Ivo A. ^{[1
]}

Verlaan-de Vries, Matty ^{[1
]}

Kelstrup, Christian D. ^{[2
]}

Francavilla, Chiara ^{[2
]}

Medema, Rene H. ^{[3
]}

Olsen, Jesper V. ^{[2
]}

Vertegaal, Alfred C. O. ^{[1
]}

机构：

[1] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2333 ZA Leiden, Netherlands

[2] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res, DK-2200 Copenhagen, Denmark

[3] Netherlands Canc Inst, Dept Cell Biol, NL-1066 CX Amsterdam, Netherlands

来源：

MOLECULAR CELL | 2014年 / 53卷 / 06期

关键词：

FORKHEAD BOX M1; CHROMOSOME SEGREGATION; MASS-SPECTROMETRY; UBIQUITIN; PHOSPHORYLATION; CANCER; IDENTIFICATION; PATHWAY; CONJUGATION; REPRESSION;

D O I：

10.1016/j.molcel.2014.02.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1053 / 1066

页数：14

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[1] A Systematic Screen for CDK4/6 Substrates Links FOXM1 Phosphorylation to Senescence Suppression in Cancer Cells [J].