Table Of ContentAdvances in Experimental Medicine and Biology 963
Van G. Wilson Editor
SUMO Regulation
of Cellular
Processes
Second Edition
Advances in Experimental Medicine
and Biology
Volume 963
Editorial Board
IRUN R. COHEN, The Weizmann Institute of Science, Rehovot, Israel
ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research, Orangeburg,
NY, USA
JOHN D. LAMBRIS, University of Pennsylvania, Philadelphia, PA, USA
RODOLFO PAOLETTI, University of Milan, Milan, Italy
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Van G. Wilson
Editor
SUMO Regulation
of Cellular Processes
Second Edition
Editor
Van G. Wilson
Department of Microbial Pathogenesis
and Immunology, College of
Medicine
Texas A&M Health Science Center
Bryan, TX, USA
ISSN 0065-2598 ISSN 2214-8019 (electronic)
Advances in Experimental Medicine and Biology
ISBN 978-3-319-50043-0 ISBN 978-3-319-50044-7 (eBook)
DOI 10.1007/978-3-319-50044-7
Library of Congress Control Number: 2017932104
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Preface
Posttranslational modification of proteins has proven to be a critical regula-
tory mechanism to control protein function, location, and interaction with
partners. In 1996 several groups independently identified a new protein modi-
fier moiety that has become known as SUMO (small ubiquitin-like modifier).
It was quickly established that SUMO is part of a larger ubiquitin superfamily
and that the enzymology of SUMO addition to substrates paralleled the
canonical ubiquitin modification pathway. Early studies in the field of
sumoylation examined single protein substrates, and the total number of
known substrates grew slowly for the first 15 years after the discovery of
SUMO. Much of this early work focused on transcription factors as they were
among the first identified substrates for sumoylation. A large literature estab-
lished a critical regulatory role for sumoylation in fine-tuning many transcrip-
tional units that impacted a variety of cellular systems including development
and differentiation; cell growth and division; DNA organization, replication,
and repair; and defense from pathogens. As would be expected given the
involvement of sumoylation in so many fundamental cellular processes,
mutations affecting the sumoylation components typically result in lethal or
severely dysfunctional phenotypes. Additionally, disruption of SUMO
homeostasis was shown to contribute to the development and establishment
of some oncogenic malignancies.
In the years since the original edition of this book, there has been an enor-
mous increase in the interest in and understanding of the widespread role of
sumoylation in biological processes. The application of proteomics
approaches in the mid-2000s rapidly expanded the identification of SUMO
substrates along with the mapping of sumoylation sites in these substrates.
This enlarged cohort of substrates revealed new pathways and processes
modulated by sumoylation and confirmed that sumoylation is a globally sig-
nificant regulator of cellular biology. It also became clear that the original
definition of a SUMO accepter site accounted for only a portion of the
mapped sites, leading to the elucidation of several other types of consensus
acceptor motifs. Other advances include an increasing appreciation of the
role of sumoylation in network coordination (mediated via SUMO-modified
proteins binding to proteins with specific SUMO-interacting motifs), of the
importance of cross talk between the SUMO and ubiquitin systems, and of
the critical contributions of sumoylation to host health and defense against
v
vi Preface
pathogens. All of these topics are addressed in revised or new chapters of this
edition, and the contributors hope that this book will provide both a strong
foundation of established information in this field and an introduction to
cutting- edge finding and unanswered questions.
Bryan, TX, USA Van G. Wilson
Contents
1 Introduction to Sumoylation ....................................................... 1
Van G. Wilson
Part I Molecular Functions
2 Roles of Sumoylation in mRNA Processing
and Metabolism ............................................................................ 15
Patricia Richard, Vasupradha Vethantham,
and James L. Manley
3 SUMO and Chromatin Remodeling ........................................... 35
David Wotton, Lucy F. Pemberton,
and Jacqueline Merrill-Schools
4 Functions of SUMO in the Maintenance
of Genome Stability ...................................................................... 51
Nicola Zilio, Karolin Eifler-Olivi, and Helle D. Ulrich
5 Regulation of Cellular Processes by SUMO:
Understudied Topics .................................................................... 89
Jorrit M. Enserink
6 The Molecular Interface Between the SUMO
and Ubiquitin Systems ................................................................. 99
Jeff L. Staudinger
7 SUMO and Nucleocytoplasmic Transport ................................. 111
Christopher Ptak and Richard W. Wozniak
8 Sumo Modification of Ion Channels ........................................... 127
Mark Benson, Jorge A. Iñiguez-lluhí, and Jeffrey Martens
9 The Roles of SUMO in Metabolic Regulation ........................... 143
Elena Kamynina and Patrick J. Stover
Part II Cell Growth Regulation
10 The SUMO Pathway in Mitosis .................................................. 171
Debaditya Mukhopadhyay and Mary Dasso
vii
viii Contents
11 Wrestling with Chromosomes: The Roles
of SUMO During Meiosis ............................................................ 185
Amanda C. Nottke, Hyun-Min Kim,
and Monica P. Colaiácovo
12 Sumoylation in Development and Differentiation ..................... 197
Adeline F. Deyrieux and Van G. Wilson
13 The Role of Sumoylation in Senescence ..................................... 215
Lyndee L. Scurr, Sebastian Haferkamp, and Helen Rizos
14 Regulation of Plant Cellular and Organismal
Development by SUMO ............................................................... 227
Nabil Elrouby
15 SUMO in Drosophila Development ............................................ 249
Joseph Cao and Albert J. Courey
Part III Diseases
16 Sumoylation: Implications for Neurodegenerative
Diseases ......................................................................................... 261
Dina B. Anderson, Camila A. Zanella, Jeremy M. Henley,
and Helena Cimarosti
17 Sumoylation and Its Contribution to Cancer ............................ 283
Jason S. Lee, Hee June Choi, and Sung Hee Baek
18 Sumoylation Modulates the Susceptibility
to Type 1 Diabetes ........................................................................ 299
Jing Zhang, Zhishui Chen, Zhiguang Zhou,
Ping Yang, and Cong-Yi Wang
19 Sumoylation in Craniofacial Disorders ...................................... 323
Erwin Pauws and Philip Stanier
20 Coordination of Cellular Localization-Dependent
Effects of Sumoylation in Regulating Cardiovascular
and Neurological Diseases ........................................................... 337
Jun-ichi Abe, Uday G. Sandhu, Nguyet Minh Hoang,
Manoj Thangam, Raymundo A. Quintana-Quezada,
Keigi Fujiwara, and Nhat Tu Le
21 Viral Interplay with the Host Sumoylation System .................. 359
Van G. Wilson
22 Sumoylation as an Integral Mechanism in Bacterial
Infection and Disease Progression .............................................. 389
Chittur V. Srikanth and Smriti Verma
Index ...................................................................................................... 409
1
Introduction to Sumoylation
Van G. Wilson
Abstract
Reversible post-translational modification is a rapid and efficient system
to control the activity of pre-existing proteins. Modifiers range from small
chemical moieties, such as phosphate groups, to proteins themselves as
the modifier. The patriarch of the protein modifiers is ubiquitin which
plays a central role in protein degradation and protein targeting. Over the
last 20 years, the ubiquitin family has expanded to include a variety of
ubiquitin-related small modifier proteins that are all covalently attached to
a lysine residue on target proteins via series of enzymatic reactions. Of
these more recently discovered ubiquitin-like proteins, the SUMO family
has gained prominence as a major regulatory component that impacts
numerous aspects of cell growth, differentiation, and response to stress.
Unlike ubiquitinylation which often leads to proteins turn over, sumoylation
performs a variety of function such as altering protein stability, modulat-
ing protein trafficking, directing protein-protein interactions, and regulat-
ing protein activity. This chapter will introduce the basic properties of
SUMO proteins and the general tenets of sumoylation.
Keywords
SUMO • Ubc9 • SAE1/2 • SENP • SUMO Ligases
1.1 The Sumo Proteins
Over two decades ago, a small cellular protein of
12 kDa, with 18% homology to the well-known
V.G. Wilson (*) ubiquitin protein, was co-discovered and termed
Department of Microbial Pathogenesis and Small Ubiquitin-like MOdifier or SUMO. SUMO
Immunology, College of Medicine, Texas A&M
was independently identified by four groups in
Health Science Center, 8447 HWY 47, Bryan,
1996: Freemont’s group found it as a small
TX 77807-1359, USA
e-mail: [email protected] ubiquitin-l ike protein associated with PML in an
© Springer International Publishing AG 2017 1
V.G. Wilson (ed.), SUMO Regulation of Cellular Processes, Advances in Experimental Medicine
and Biology 963, DOI 10.1007/978-3-319-50044-7_1
