24 February 2014

SUMOylation Dynamics during Cell-Cycle Progression

The group of Prof. Jesper V. Olsen at Novo Nordisk Foundation Center for Protein Research at University of Copenhagen has in collaboration with the group of Associate Prof. Alfred Vertegaal at Leiden University Medical Center performed a global analysis of SUMOylation (small ubiquitin-like modification) targets in the cell-cycle by quantitative proteomics and high-resolution mass spectrometry. The study identified more than five hundred proteins that are targeted by SUMOylation including more than two hundred SUMO-2 acceptor sites. This is the largest set of SUMOylation sites identified to date. The dataset revealed that SUMOylation is a Protein Group Modification that targets proteins in complexes with known roles in the cell-cycle. For example, Forkhead box transcription factor M1 (FoxM1), a key regulator of cell-cycle progression and chromosome segregation, was identified as a mitotic SUMO target Protein. SUMOylation of FoxM1 peaks during G2 and M phase, when FoxM1 transcriptional activity is required. Functional analysis demonstrated that SUMOylation of the FoxM1 enhances its transcriptional activity by blocking the dimerization of FoxM1, and thereby relieving FoxM1 autorepression. The dataset underlines the important role of post-translation modifications such as SUMOylation in regulating cell-cycle progression. This collaborative project is part of UPStream, an EU-funded Marie Curie International Training Network, focusing on investigating the essential roles of Ubiquitin-like molecules and the Ubiquitin Proteasome System. The study has been published in Molecular Cell.

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

Authors: Joost Schimmel, Karolin Eifler, Jon Otti Sigurðsson, Sabine A.G. Cuijpers, Ivo A. Hendriks, Matty Verlaan-de Vries, Christian D. Kelstrup, Chiara Francavilla, Rene H. Medema, Jesper V. Olsen* and Alfred C.O. Vertegaal*
*Correspondence: jesper.olsen@cpr.ku.dk (J.V.O.), vertegaal@lumc.nl (A.C.O.V.)