Wilson / Willson SUMO Regulation of Cellular Processes

2009
ISBN: 978-90-481-2649-1
Verlag: Springer Netherland
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 339 Seiten, eBook

Over a decade ago, a small cellular protein of 12 kDa, with 18% homology to the well-known ubiquitin protein, was co-discovered and termed Small Ubiquitin-like Modifier, or SUMO. Sumoylation is a post-translational modification that utilizes SUMO as the modifier group covalently attached to target substrates. This state-of-the art review on the sumoylation system deals with protein modification as it pertains to regulation of diverse cellular functions. Each chapter has been written by a leading researcher and covers the role of sumoylation in fundamental biochemical activities (transcription, RNA processing, chromatin remodelling, DNA repair, nucleocytoplasmic transport, ion channel regulation, and metabolic pathways). The text also examines the part sumoylation plays in critical cellular processes such as mitosis, meiosis, differentiation, senescence, and apoptosis. Lastly, the emerging role of sumoylation in specific diseases, including cancer and diabetes as well as neurodegenerative ones, is explored with an emphasis on defining molecular mechanisms that may provide new targets for treatment or prevention. While SUMO was discovered more than 10 years ago, this is still a relatively young field, and much remains to be discovered about the biochemical and biological properties of this modification system. In just the last few years, it has become clear that sumoylation modifies hundreds of cellular proteins, and there has been increased appreciation for the breadth of cellular functions that are impacted by this post-translational modification.

Zielgruppe

Research

Autoren/Hrsg.

Wilson, Van

Wilson, Van G.

Willson, Victor

Inhaltsverzeichnis

1;Contents;4
2;Contributors;6
3;1 Introduction to Sumoylation;9
3.1;1.1 The SUMO Proteins;9
3.2;1.2 The Enzymology of Sumoylation;11
3.3;1.3 Sumoylation Functions;13
3.4;1.4 Conclusion;14
3.5;References;15
4;Part I Molecular Functions;19
4.1;2 SUMO Modification and Transcriptional Regulation;20
4.1.1;2.1 Introduction;20
4.1.2;2.2 Sumoylation of Sequence Specific Regulators;24
4.1.2.1;2.2.1 Direct Effects on DNA Binding: HSF2;24
4.1.2.2;2.2.2 Sumoylation of Precursors and Regulatory Subunits: NF B ;25
4.1.2.3;2.2.3 Sumo as a Modulator of Transcriptional Regulatory Potential;25
4.1.2.3.1;2.2.3.1 Effect on Activators;26
4.1.2.3.2;2.2.3.2 Basis for the Promoter Context Dependence of Sumoylation;27
4.1.2.3.3;2.2.3.3 Sumoylation of Repressors: Positive Effects;28
4.1.2.3.4;2.2.3.4 Sumoylation of Repressors: Negative Effects;30
4.1.3;2.3 SUMO Harbors an Intrinsic Transcriptional Inhibitory Function;31
4.1.3.1;2.3.1 Identification of an Effector Surface in SUMO That Interacts with Sumo Binding Motifs;32
4.1.3.2;2.3.2 What Are the Mediators of the Repressive Effects of SUMO?;33
4.1.4;2.4 Sumoylation of Coregulators;35
4.1.4.1;2.4.1 Coactivators;36
4.1.4.2;2.4.2 Corepressors;38
4.1.5;2.5 How Does SUMO Modification Exerts Significant Effects at Low Stoichiometries?;40
4.1.6;2.6 Coda;42
4.1.7;References;43
4.2;3 Emerging Roles for SUMO in mRNA Processing and Metabolism;48
4.2.1;3.1 A Brief Introduction to RNA Processing Events, Interconnections to Transcription and Export;48
4.2.2;3.2 RNA Processing Factors as Sumoylation Substrates;49
4.2.3;3.3 5 Capping;50
4.2.4;3.4 Splicing;53
4.2.5;3.5 3 End Processing;54
4.2.6;3.6 Sumoylation of hnRNPS;57
4.2.7;3.7 Extending the Role of SUMO to mRNA Export;58
4.2.8;3.8 SUMO and RNA Editing;59
4.2.9;3.9 Conclusions;59
4.2.10;References;60
4.3;4 SUMO and Chromatin Remodelling;65
4.3.1;4.1 Introduction;66
4.3.2;4.2 Histone Sumoylation;66
4.3.3;4.3 SUMO and Higher Order Chromatin Structure;68
4.3.4;4.4 Telomeres and Centromeres;70
4.3.5;4.5 SUMO-Dependent Recruitment of General Transcriptional Corepressors;72
4.3.5.1;4.5.1 SUMO-Dependent HDAC Recruitment;72
4.3.5.2;4.5.2 Corepressor Complex Recruitment;73
4.3.6;4.6 SUMO-Dependent Modulation of General Coregulator Activity;74
4.3.6.1;4.6.1 HDAC Sumoylation and HDAC-Dependent Sumoylation;74
4.3.6.2;4.6.2 Sumoylation of General Transcriptional Corepressors;75
4.3.7;4.7 The Role of SUMO E3 Ligases in Chromatin Remodelling;76
4.3.8;References;78
4.4;5 Functions of SUMO in the Maintenance of Genome Stability;83
4.4.1;5.1 Introduction;84
4.4.2;5.2 Effects of SUMO on Homologous Recombination;85
4.4.2.1;5.2.1 Mms21-Dependent Sumoylation;86
4.4.2.2;5.2.2 Sumoylation of Rad52;86
4.4.2.3;5.2.3 Sumoylation of PCNA;88
4.4.3;5.3 Sumoylation of Thymidine DNA Glycosylase in Base Excision Repair;89
4.4.4;5.4 Function of SUMO in the Maintenance of Telomere Length;90
4.4.5;5.5 Sumoylation of Topoisomerase II in Chromosome Segregation;92
4.4.6;5.6 Function of Poly-SUMO Chains in DNA Repair;94
4.4.7;5.7 Conclusion;96
4.4.8;References;97
4.5;6 SUMO and Nucleocytoplasmic Transport;103
4.5.1;6.1 Introduction;103
4.5.2;6.2 Compartment-Specific Sumoylation;106
4.5.3;6.3 Regulation of Nuclear Transport by Sumoylation;108
4.5.3.1;6.3.1 SUMO-Dependent Inhibition of Nuclear Export;109
4.5.3.2;6.3.2 SUMO-dependent Stimulation of Nuclear Export;112
4.5.3.3;6.3.3 Sumoylation and Nuclear Import;112
4.5.4;6.4 Control of the Nuclear Transport Machinery by Sumoylation;114
4.5.5;6.5 Nucleocytoplasmic Transport of SUMO-Specific Enzymes;115
4.5.6;6.6 Conclusion;116
4.5.7;References;117
4.6;7 SUMO Modification of Ion Channels;123
4.6.1;7.1 Introduction;123
4.6.2;7.2 Extranuclear Targets of Sumoylation;125
4.6.3;7.3 Sumoylation of Ion Channels;127
4.6.3.1;7.3.1 K2P1;127
4.6.3.2;7.3.2 Kv1.5;131
4.6.3.3;7.3.3 GluR6;133
4.6.4;7.4 Ion Channels as Probes of SUMO Modification at the Plasma Membrane;135
4.6.5;7.5 Conclusions;139
4.6.6;References;140
4.7;8 The Roles of SUMO in Metabolic Regulation;143
4.7.1;8.1 Introduction: Functions of SUMO in Metabolism;144
4.7.2;8.2 SUMO and Master Regulation of Lipid Biosynthesis;144
4.7.3;8.3 Metabolic Adaptation to Cellular and Oxidative Stress;146
4.7.4;8.4 SUMO and Energy Metabolism;147
4.7.4.1;8.4.1 SUMO and Muscle Metabolism;147
4.7.4.2;8.4.2 SUMO and Insulin Synthesis;148
4.7.4.3;8.4.3 SUMO and Glucose Transport;149
4.7.4.4;8.4.4 Mitochondrial Biogenesis and Metabolic Disease;150
4.7.5;8.5 SUMO and Folate-Mediated One-Carbon Metabolism;151
4.7.6;References;153
5;Part II Cell Growth Regulation;156
5.1;9 The SUMO Pathway in Mitosis;157
5.1.1;9.1 Introduction;157
5.1.2;9.2 The SUMO Pathway;158
5.1.3;9.3 Outcomes of SUMO Modification;159
5.1.4;9.4 The Role of SUMO in Mitotic Chromosome Structure;160
5.1.5;9.5 SUMO and Centromere/Kinetochore Organization;163
5.1.6;9.6 SUMO and Cytokinesis;167
5.1.7;9.7 Conclusions and Perspectives;168
5.1.8;References;169
5.2;10 Wrestling with Chromosomes: The Roles of SUMODuring Meiosis;174
5.2.1;10.1 Introduction;174
5.2.2;10.2 Sumoylation;175
5.2.2.1;10.2.1 Sumoylation in Meiosis: A Phenotypic Survey;177
5.2.2.2;10.2.2 Targets of Sumoylation in Meiosis;179
5.2.3;10.3 Centromeric Heterochromatin and Sumoylation;179
5.2.4;10.4 Centromeric Coupling;180
5.2.5;10.5 SUMO-Mediated Regulation of SC Dynamics;182
5.2.5.1;10.5.1 ZIP1 and ZIP3: A SUMO Connection;182
5.2.6;10.6 Meiotic DSB Repair/Recombination;184
5.2.7;10.7 Conclusions;185
5.2.8;References;186
5.3;11 Sumoylation in Development and Differentiation;189
5.3.1;11.1 Introduction;189
5.3.2;11.2 The Reproductive System;190
5.3.2.1;11.2.1 Gonadal, Uterine, and Vuval Morphogenesis;190
5.3.2.2;11.2.2 Sperm Differentiation;191
5.3.3;11.3 Stem Cell Differentiation;193
5.3.3.1;11.3.1 Embryonic Stem Cells Diffentiation;193
5.3.3.2;11.3.2 Hematopoietic Stem Cells -- Macrophage Differentiation;194
5.3.4;11.4 Tissue and Cellular Differentiation;195
5.3.4.1;11.4.1 Keratinocytes;195
5.3.4.2;11.4.2 Myocytes;196
5.3.4.3;11.4.3 Neuronal Cells;197
5.3.5;11.5 Conclusions;198
5.3.6;References;199
5.4;12 The Role of Sumoylation in Senescence;202
5.4.1;12.1 Introduction;202
5.4.2;12.2 Sumoylation and Senescence;205
5.4.3;12.3 Cellular Senescence and p53 Sumoylation;207
5.4.4;12.4 Sumoylation, Senescence, and the Retinoblastoma Protein;208
5.4.5;12.5 Role of PML and Sumoylation in the Regulation of Senescence;210
5.4.6;12.6 Telomere Maintenance and SUMO;211
5.4.7;12.7 Conclusions;212
5.4.8;References;213
5.5;13 Sumoylation and Apoptosis;218
5.5.1;13.1 Introduction;218
5.5.2;13.2 p53 as a Major Apoptosis Regulatory Gene;219
5.5.2.1;13.2.1 P53 and Hematological Malignancies;220
5.5.2.2;13.2.2 Nutlin-3 Dependent Apoptosis;221
5.5.3;13.3 Aging and Apoptosis;223
5.5.4;13.4 Hormone Nuclear Receptor and Acetylation/Sumoylation;224
5.5.5;13.5 Sumoylation and Mitochondria-Associated Apoptosis;225
5.5.6;13.6 Topoisomerase as a Target of Apoptosis;226
5.5.7;13.7 Signalling Pathways and Sumoylation/Apoptosis;226
5.5.8;13.8 Conclusion;229
5.5.9;References;229
6;Part III Diseases;232
6.1;14 The Role of Sumoylation in Neurodegenerative Diseases;233
6.1.1;14.1 Introduction;233
6.1.2;14.2 Parkinsons Disease;234
6.1.3;14.3 Alzheimers Disease;236
6.1.4;14.4 Polyglutamine Diseases;237
6.1.4.1;14.4.1 Huntington's Disease;238
6.1.4.2;14.4.2 Denatorubro-Pallidoluysian Atrophy;238
6.1.4.3;14.4.3 Spinobulbar Muscular Atrophy;239
6.1.4.4;14.4.4 Spinocerebellar Ataxias;239
6.1.5;14.5 Neuronal Intranuclear Inclusion Disease;240
6.1.6;14.6 Cellular Stress;241
6.1.7;14.7 Ischemia;242
6.1.8;14.8 Sumoylation as a Potential Drug Target;243
6.1.9;14.9 Conclusions and Perspectives;246
6.1.10;References;247
6.2;15 Sumoylation and Its Contribution to Cancer;252
6.2.1;15.1 Introduction;252
6.2.2;15.2 Upstream Signals Regulating SUMO-Conjugation System in Cancer;253
6.2.3;15.3 Regulation of SUMO E2 Conjugating Enzyme, UBC9, in Cancer;255
6.2.4;15.4 Involvement of SUMO E3 Ligases in Cancer;256
6.2.5;15.5 Involvement of SUMO-Specific Proteases in Cancer;257
6.2.6;15.6 Regulation of Sumoylation at the Substrate Level and Implications in Cancer;258
6.2.7;15.7 SUMO Modification of Oncogenes and Tumor Suppressors;259
6.2.8;15.8 Conclusions;264
6.2.9;References;264
6.3;16 SUMO4-Encoded Genetic Susceptibility to Type 1 Diabetes;272
6.3.1;16.1 Introduction;273
6.3.2;16.2 Characterization of SUMO4 in T1D Susceptibility;274
6.3.3;16.3 Genetic Heterogeneity for SUMO4 in the European Caucasians;276
6.3.4;16.4 validation of SUMO4 as a Novel T1D Susceptibility Gene;277
6.3.5;16.5 The Effect of M55V Supports SUMO4 in T1D Susceptibility;280
6.3.6;16.6 Stress-Dependent SUMO4 Functionality;281
6.3.7;16.7 SUMO4 Acts as a Negative Regulator for the NFB Signaling Pathway;282
6.3.8;16.8 SUMO4 Regulates Cytokine-Initiated JAK/STAT Signaling;284
6.3.9;16.9 SUMO4 Modulates AP-1 Tanscriptional Activity;285
6.3.10;16.10 SUMO4 Wrestles with Intracellular Stress;287
6.3.11;16.11 Conclusions;289
6.3.12;References;289
6.4;17 Sumoylation in Craniofacial Disorders;299
6.4.1;17.1 Key Role for SUMO in Development;299
6.4.2;17.2 SUMO1 Haploinsufficiency Causes Cleft Lip and/or Palate;300
6.4.3;17.3 Sumoylation Regulates Craniofacial Developmental Genes;301
6.4.4;17.4 SUMO in Developmental Pathways and Syndromes;304
6.4.5;17.5 SUMO, Stress and CL/P;306
6.4.6;17.6 Conclusions;307
6.4.7;References;307
6.5;18 Viral Interplay with the Host Sumoylation System;312
6.5.1;18.1 Modification of Viral Proteins by Sumoylation;312
6.5.2;18.2 Viral Proteins that Affect Host Sumoylation;315
6.5.3;18.3 Herpes Simplex Virus;315
6.5.4;18.4 Cytomegalovirus;316
6.5.5;18.5 Human Herpesvirus 6;317
6.5.6;18.6 Epstein-Barr Virus;318
6.5.7;18.7 Adenovirus;318
6.5.8;18.8 Human Papillomavirus;320
6.5.9;18.9 Conclusion;322
6.5.10;References;323
6.6;Index;327