Cover Page
The handle http://hdl.handle.net/1887/28466 holds various files of this Leiden University
dissertation
Author: Hendriks, Ivo Alexander
Title: Global and site-specific characterization of the SUMO proteome by mass
spectrometry
Issue Date: 2014-09-03
Global and Site-Specific
Characterization of the SUMO
Proteome by Mass Spectrometry
Ivo Hendriks
Cover design by IA Hendriks
Thesis layout by IA Hendriks
Printing by GVO drukkers & vormgevers B.V. | Ponsen & Looijen, www.gvo.nl
ISBN/EAN: 978-90-6464-804-5
Copyright 2014, Ivo Hendriks. All rights reserved. Copyright of individual chapters
lies with the first and last authors, excepting the following:
Chapters 4 and 5: Elsevier (Molecular Cell)
No part of this book may be reproduced, digitalized, or transmitted in any form
or by any means, electronic or mechanical, including photocopying, recording, or
by any information storage or retrieval system, without prior permission from the
author.
Global and Site-Specific
Characterization of the SUMO
Proteome by Mass Spectrometry
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van de Rector Magnificus Prof.mr. C.J.J.M. Stolker,
volgens het besluit van het College voor Promoties
te verdedigen op woensdag 3 september 2014
klokke 13.45 uur
door
Ivo Alexander Hendriks
geboren te Haarlem
op 17 oktober 1983
Promotiecommissie
Promotor:
Prof. Dr. P. ten Dijke
Copromotor:
Dr. A.C.O Vertegaal
Overige leden: Prof. Dr. H.T.M. Timmers1
Prof. Dr. M. Vermeulen2
Prof. Dr. L. Mullenders
Department of Molecular Cancer Research, University Medical Center Utrecht, Utrecht, Netherlands
Radboud Institute for Moleculair Life Sciences, Nijmegen, Netherlands
1
2
The studies described in this thesis were primarily performed at the Leiden University Medical Center (Netherlands), and in part at the Max Planck Institute for
Biochemistry (Germany) and at the Novo Nordisk Foundation Center for Protein
Research (Denmark).
This work was financially supported as indicated in each chapter. Overall, these
studies were financially supported by the Netherlands Organization for Scientific
Research (NWO)(A.C.O.V.), ZonMW (A.C.O.V.), the European Research Council
(A.C.O.V), the Marie Curie Initial Training Networks program of the European Union
(290257-UPStream, A.C.O.V. and J.V.O.), the research career program FSS Sapere
Aude (J.V.O.) from the Danish Research Council, the RUBICON EU Network of Excellence (M.M.), and the Max Planck Society (M.M).
Printing of this thesis was financially supported by the J.E. Jurriaanse Stichting.
"Yesterday we obeyed kings and
bent our necks before emperors.
Today we kneel only to truth."
Kahlil Gibran
(January 6, 1883 – April 10, 1931)
TABLE OF CONTENTS
Outline of the thesis
11
Chapter 1
Introduction
15
Chapter 2
SUMO-2 Orchestrates Chromatin Modifiers in Response to DNA Damage
43
Chapter 3
USP11 Counteracts RNF4 and Stabilizes PML Nuclear Bodies
77
Chapter 4
Site-Specific Identification of SUMO-2 Targets in Cells Reveals an Inverted SUMOylation Motif and a Hydrophobic Cluster SUMOylation Motif
Chapter 5
Uncovering SUMOylation Dynamics During Cell Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein
103
139
Chapter 6
Uncovering Global SUMOylation Signalling Networks in a Site-Specific Manner
181
Chapter 7
A Novel Method for the Identification of SUMO Acceptor Lysines in a Site-Specific Manner
219
Chapter 8Discussion
249
Summary
275
Nederlandse samenvatting
279
List of abbreviations
287
Curriculum Vitae
293
List of publications
295
Acknowledgments
297
9
10