Bradshaw / Dennis Regulation of Organelle and Cell Compartment Signaling

Cell Signaling Collection
1. Auflage 2011
ISBN: 978-0-12-382214-7
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 550 Seiten, Web PDF

This must-have cell signaling title will appeal to researchers across molecular biology, biochemistry, cell biology and genetics. The articles are written and edited by experts in the field and emphasize signaling to and from intracellular compartments including transcriptional responses to cytoplasmic and nuclear signaling events, chromatin remodeling and stress responses, the regulation of endoplasmic reticulum function, control of cell cycle progression and apoptosis and the modulation of the activities of mitochondria and other organelles. - Articles written and edited by experts in the field - Thematic volume covering regulation of endoplasmic reticulum function, regulation of cell cycle progression, and quality control and assurance in mitochondrion events - Up-to-date research on events in membrane proteins and proteins of intracellular matrix

Autoren/Hrsg.

Bradshaw, Ralph A.

Dennis, Edward A.

Inhaltsverzeichnis

1;Front Cover;1
2;Regulation of Organelle and Cell Compartment Signaling;4
3;Copyright Page;5
4;Editorial Advisory Board;6
5;Contents;8
6;Preface;12
7;Contributors;14
8;Section A: Overview;20
8.1;Chapter 1: Organelle Signaling;22
8.1.1;Origins of Cell Signaling Research;22
8.1.2;Receptors and Intracellular Signaling;23
8.1.3;Transcriptional Responses;24
8.1.4;Organelle Signaling;25
8.1.5;Focus and Scope of this Volume;26
8.1.6;References;26
9;Section B: Nuclear Signaling;28
9.1;Part 1: Transcription;30
9.1.1;Chapter 2: Signaling at the Nuclear Envelope;32
9.1.1.1;Introduction;32
9.1.1.2;Lamins and Lamin Associated Proteins in Cell Signaling;33
9.1.1.3;The Npc in Cell Signaling;36
9.1.1.4;Conclusions;36
9.1.1.5;Acknowledgements;36
9.1.1.6;References;37
9.1.2;Chapter 3: Nuclear Receptor Coactivators;40
9.1.2.1;Introduction;40
9.1.2.2;Ligand-Dependent Interaction between Nuclear Receptors and Coactivators;40
9.1.2.3;Posttranslational Modifications Performed by Coactivator Complexes;42
9.1.2.4;Conclusions;43
9.1.2.5;References;43
9.1.3;Chapter 4: Corepressors in Mediating Repression by Nuclear Receptors;46
9.1.3.1;Introduction;46
9.1.3.2;Corepressors Bound to Unliganded Receptor;47
9.1.3.3;Transrepression Strategies;49
9.1.3.4;Corepressors as Metabolic Sensors;50
9.1.3.5;Disease Mechanisms of Nuclear Receptor Dependent Transrepression;51
9.1.3.6;Future Directions;52
9.1.3.7;References;52
9.1.4;Chapter 5: Steroid Hormone Receptor Signaling;56
9.1.4.1;Introduction;56
9.1.4.2;Activation by the Hormone;56
9.1.4.3;Hormone Independent Activation;57
9.1.4.4;Cross-Talk with Other Transcription Factors;57
9.1.4.5;Non-Genomic Action of Steroid Hormones;57
9.1.4.6;The Errs;57
9.1.4.7;Selective Steroid Hormone Receptor Modulators;58
9.1.4.8;Acknowledgements;58
9.1.4.9;References;58
9.1.5;Chapter 6: FOXO Transcription Factors: Key Targets of the PI3K-Akt Pathway that Regulate Cell Proliferation, Survival,and Organismal Aging;62
9.1.5.1;Introduction;62
9.1.5.2;Identification of the Foxo Subfamily of Transcription Factors;62
9.1.5.3;Regulation of Foxo Transcription Factors by the PI3K-Akt Pathway;62
9.1.5.4;Other Regulatory Phosphorylation Sites in Foxos;63
9.1.5.5;Mechanism of the Exclusion of Foxos from the Nucleus in Response to Growth Factor Stimulation;63
9.1.5.6;Transcriptional Activator Properties of Foxos;65
9.1.5.7;Foxos and the Regulation of Apoptosis;65
9.1.5.8;Foxos are Key Regulators of Several Phases of the Cell Cycle;65
9.1.5.9;Foxos in Cancer Development: Potential Tumor Suppressors;67
9.1.5.10;Role of Foxos in the Response to stress and Organismal Aging;67
9.1.5.11;Foxos and the Regulation of Metabolism in Relation to Organismal Aging;67
9.1.5.12;Conclusion;68
9.1.5.13;Acknowledgements;68
9.1.5.14;References;68
9.1.6;Chapter 7: The Multi-Gene Family of Transcription Factor AP-1;72
9.1.6.1;Introduction;72
9.1.6.2;General Structure of the AP-1 Subunits;72
9.1.6.3;Transcriptional And posttranslational Control of AP-1 Activity;73
9.1.6.4;Function of Mammalian AP-1 Subunits During Embryogenesis and Tissue Homeostasis: Lessons From Loss-of-Function and Gain-of-Function Approaches in Mice;74
9.1.6.5;Function of Mammalian AP-1 Subunits During Cancer Development and Progression;78
9.1.6.6;Conclusion;79
9.1.6.7;Acknowledgements;79
9.1.6.8;References;79
9.1.7;Chapter 8: NF.B: A Key Integrator of Cell Signaling;82
9.1.7.1;References;87
9.1.8;Chapter 9: Ubiquitin-mediated Regulation of Protein Kinases in NF.B Signaling;90
9.1.8.1;Introduction;90
9.1.8.2;The Ubiquitin Pathway;90
9.1.8.3;NF.B Signaling;91
9.1.8.4;Ubiquitin-Mediated Activation of Protein Kinases in the IL-1R and TLR Pathways;92
9.1.8.5;Ubiquitin-Mediated Regulation of NF.B and Apoptosis in the TNFa Pathway;93
9.1.8.6;De-Ubiquitination Enzymes Prevent Protein Kinases Activation in The NF.B Pathway;95
9.1.8.7;Polyubiquitination Regulates Protein Kinase Activation in Diverse NF.B Pathways;96
9.1.8.8;Conclusions And Perspectives;98
9.1.8.9;Acknowledgements;98
9.1.8.10;References;98
9.1.9;Chapter 10: Transcriptional Regulation via the cAMP Responsive Activator CREB;102
9.1.9.1;The Creb Family of Transcription Factors;102
9.1.9.2;Domain Structure and Function;102
9.1.9.3;Overview of CREB Activation;103
9.1.9.4;Key Phosphorylation Events;103
9.1.9.5;CREB Target Genes;103
9.1.9.6;CBP and P300;104
9.1.9.7;TORC;104
9.1.9.8;Other Coactivators and Interacting Proteins;104
9.1.9.9;Questions to be Addressed;105
9.1.9.10;Acknowledgements;105
9.1.9.11;References;105
9.1.10;Chapter 11: The NFAT Family: Structure, Regulation, and Biological Functions;108
9.1.10.1;Introduction;108
9.1.10.2;Structure and DNA Binding;108
9.1.10.3;Regulation;109
9.1.10.4;Transcriptional Functions;111
9.1.10.5;Biological Programs Regulated By NFAT;111
9.1.10.6;The Primordial Family Member: NFAT5;112
9.1.10.7;Perspectives;113
9.1.10.8;References;113
9.1.11;Chapter 12: JAK-STAT Signaling;118
9.1.11.1;Abbreviations;118
9.1.11.2;Introduction;118
9.1.11.3;The JAK-STAT Paradigm;118
9.1.11.4;The JAK Family;121
9.1.11.5;The STAT Family;122
9.1.11.6;A Bright Future;123
9.1.11.7;References;123
9.2;Part 2: Chromatin Remodeling;126
9.2.1;Chapter 13: Histone Acetylation Complexes;128
9.2.1.1;Introduction;128
9.2.1.2;KAT Classification and Diversity;129
9.2.1.3;Bromodomains and Other Interpreters of Histone Modifications;134
9.2.1.4;Kats and Disease;134
9.2.1.5;Conclusion and Future Directions;135
9.2.1.6;Acknowledgements;135
9.2.1.7;References;135
9.2.2;Chapter 14: Regulation of Histone Deacetylase Activities and Functions by Phosphorylation and Dephosphorylation;138
9.2.2.1;Introduction;138
9.2.2.2;Reversible Phosphorylation of Mammalian Class I Hdacs;139
9.2.2.3;Reversible Phosphorylation of Mammalian Class II Hdacs;142
9.2.2.4;Conclusion and Perspectives;144
9.2.2.5;References;145
9.2.3;Chapter 15: Histone Methylation: Chemically Inert but Chromatin Dynamic;148
9.2.3.1;Introduction;148
9.2.3.2;Historical Perspective of Chromatin and Histone Methylation;148
9.2.3.3;Enzymes Regulating Arginine and Lysine Methylation States;149
9.2.3.4;Histone Lysine Methyltransferases;151
9.2.3.5;Histone Demethylase Enzymes;151
9.2.3.6;Degree and Location Matter;153
9.2.3.7;References;154
9.2.4;Chapter 16: Histone Phosphorylation: Chromatin Modifications that Link Cell Signaling Pathways to Nuclear Function Regulation;158
9.2.4.1;Introduction;158
9.2.4.2;Histone Phosphorylation and Transcriptional Regulation;159
9.2.4.3;Downstream Effects of Transcription Associated H3 Phosphorylation;161
9.2.4.4;Histone Phosphorylation in Response to DNA Damage;162
9.2.4.5;Histone Phosphorylation and Mitosis;163
9.2.4.6;Histone Phosphorylation During Apoptosis;163
9.2.4.7;Histone Phosphorylation and Human Diseases;164
9.2.4.8;Conclusions and Perspectives;164
9.2.4.9;References;165
9.2.5;Chapter 17: Histone Variants: Signaling or Structural Modules?;168
9.2.5.1;Introduction;168
9.2.5.2;H2A.Bbd in Search of a Function;169
9.2.5.3;H2A.X: DNA Damage and Beyond;170
9.2.5.4;H2A.Z Function at a Flip of a Coin;171
9.2.5.5;Macro H2A: Phosphorylation Matters;172
9.2.5.6;H2B Variance and Unknown Partners;173
9.2.5.7;H3.3 Providing Transcriptional Memory;174
9.2.5.8;CENP-A: Splitting Nucleosomes in Drosophila;174
9.2.5.9;Histone H1: The Microheterogeneity of Specialized Function;176
9.2.5.10;Concluding Remarks;177
9.2.5.11;Acknowledgements;178
9.2.5.12;References;178
9.2.6;Chapter 18: Histone Ubiquitination;186
9.2.6.1;The Mechanism of Ubiquitination;186
9.2.6.2;Histone Ubiquitination;186
9.2.6.3;Mono-Ubiquitination of H2A;186
9.2.6.4;Ubiquitination of Histone H2A Variants;187
9.2.6.5;De-Ubiquitination of Ubh2A;188
9.2.6.6;How does UbH2A Repress Transcription?;189
9.2.6.7;The Role of UbH2A in DNA Repair;189
9.2.6.8;Mono-Ubiquitination of H2B;189
9.2.6.9;H2B Ubiquitination Requires Factors Involved in Transcription Initiation and Elongation;190
9.2.6.10;H2B Ubiquitination is Required for Processive Lys-4 H3 and Lys-79 H3 Methylation;191
9.2.6.11;The 19S Proteasome and the Ccr4-not Complex Link H2B Ubiquitination to Lys-4 and Lys-79 H3 Methylation;192
9.2.6.12;De-Ubiquitination of UbH2B;192
9.2.6.13;De-Ubiquitination of UbH2B is Required for Later Stages of Transcription Elongation;193
9.2.6.14;Conclusion;193
9.2.6.15;Acknowledgements;194
9.2.6.16;References;194
9.2.7;Chapter 19: Chromatin Mediated Control of Gene Expression in Innate Immunity and Inflammation;198
9.2.7.1;Introduction;198
9.2.7.2;Inflammation as a Kinetically Complex Transcriptional Response;198
9.2.7.3;Chromatin and the Kinetic Control of Inflammatory Responses;199
9.2.7.4;Genetic Dissection of Chromatin Remodeling at Inflammatory Genes;199
9.2.7.5;Binding of Inflammatory Transcription Factors to Nucleosomal DNA;200
9.2.7.6;Conclusions;202
9.2.7.7;References;203
9.3;Part 3: Stress Responses;204
9.3.1;Chapter 20: Complexity of Stress Signaling;206
9.3.1.1;Abbreviations;206
9.3.1.2;Introduction;206
9.3.1.3;Origin of Stress Response Signals;207
9.3.1.4;Signal Transduction;211
9.3.1.5;Systems Level Deductions of Stress Response Networks;214
9.3.1.6;Acknowledgements;217
9.3.1.7;References;217
9.3.2;Chapter 21: Oxidative Stress and Free Radical Signal Transduction;226
9.3.2.1;Introduction: Redox Biology;226
9.3.2.2;Oxidative Stress Responses in Bacteria: Some Well-Defined Models of Redox Signal Transduction;226
9.3.2.3;Response to Superoxide Stress and Nitric Oxide: SoxR Protein;226
9.3.2.4;Response to H2O2 and Nitrosothiols:Oxyr Protein;229
9.3.2.5;Parallels in Redox and Free Radical Sensing;230
9.3.2.6;Themes in Redox Sensing;230
9.3.2.7;Acknowledgements;230
9.3.2.8;References;231
9.3.3;Chapter 22: Double-Strand Break Recognition and its Repair by Non-Homologous End-Joining;234
9.3.3.1;Overview of Non-Homologous End-Joining (NHEJ);234
9.3.3.2;Kinase Activation and Autophosphorylation of DNA-PK;234
9.3.3.3;DNA-PK May Influence the Balance of HR and NHEJ during S Phase;237
9.3.3.4;Local Chromatin Structure at Sites of NHEJ;238
9.3.3.5;References;238
9.3.4;Chapter 23: ATM Mediated Signaling Defends the Integrity of the Genome;240
9.3.4.1;Introduction;240
9.3.4.2;Sensing Radiation Damage in DNA;241
9.3.4.3;Atm Activation and Recruitment of DNA Damage Response Proteins to DNA DSB;242
9.3.4.4;ATM Mediated Downstream Signaling;243
9.3.4.5;Cell Cycle Checkpoint Activation;246
9.3.4.6;Concluding Remarks;248
9.3.4.7;References;248
9.3.5;Chapter 24: Signaling to the p53 Tumor Suppressor through Pathways Activated by Genotoxic and Non-Genotoxic Stresses;254
9.3.5.1;Introduction;254
9.3.5.2;p53 Protein Structure;254
9.3.5.3;Posttranslational Modifications to p53;256
9.3.5.4;Regulation of p53 Activity;257
9.3.5.5;p53 Stabilization;257
9.3.5.6;p53 Activation;259
9.3.5.7;Activation of p53 by Genotoxic Stresses;260
9.3.5.8;DNA Doubled-Strand Breaks;260
9.3.5.9;Replication Stress and Singlestranded DNA;261
9.3.5.10;Replicative Senescence;262
9.3.5.11;Oncogene Activation;262
9.3.5.12;Other Genotoxic Agents;263
9.3.5.13;Activation of p53 by Non-Genotoxic Stresses;263
9.3.5.14;The Unfolded Protein Response – ER Stress;263
9.3.5.15;Hypoxia;263
9.3.5.16;Glucose Deprivation – Nutritional Stress;264
9.3.5.17;Ribonucleotide Pool Imbalance;265
9.3.5.18;Nucleolar and Ribosomal Stress;265
9.3.5.19;Microtubule Disruption;266
9.3.5.20;Setting Thresholds and Resetting Activation – p53 Phosphatases;266
9.3.5.21;Conclusions;267
9.3.5.22;Acknowledgements;267
9.3.5.23;References;268
9.3.6;Chapter 25: The p53 Master Regulator and Rules of Engagement with Target Sequences;274
9.3.6.1;Introduction;274
9.3.6.2;The p53 Induced Transcriptional Network: Genes, Biological Functions, and the Complexity of Target Selection;274
9.3.6.3;Yeast as an in Vivo Test Tube to Study Wild-Type and Mutant p53 Transactivation Potential toward Defined Response Element Sequences;275
9.3.6.4;Yeast as an in Vivo Test Tube to Study Wild-Type and Mutant p53 Transactivation Potential Toward Defined Response Element Sequences;275
9.3.6.5;Rules of p53 Transactivation Revealed by Yeast-Based Assays;276
9.3.6.6;Spacers Affect p53 Transactivation Potential in the Yeast-Based Assay;277
9.3.6.7;Spacer Effects on p53 Binding and Transactivation in Mammalian Cell Assays;278
9.3.6.8;Non-Canonical 3/4- and 1/2-Site Res Expand the p53 Transcriptional Network;279
9.3.6.9;Impact of 1/2-Site res in the p53 Transcriptional Network;280
9.3.6.10;Evolutionary Development of p53 Res;280
9.3.6.11;Yeast Based Functional Classification of p53 Mutant Alleles Associated with Cancer;280
9.3.6.12;Contributions to the Rules of Engagement by p53 Homologs and Other Sequence Specific Transcription Factors;281
9.3.6.13;p53 Cofactors Contribute to Promoter Selectivity;281
9.3.6.14;Conclusions;281
9.3.6.15;Acknowledgements;282
9.3.6.16;References;282
9.3.7;Chapter 26: The Heat Shock Response and the Stressof Misfolded Proteins;286
9.3.7.1;Introduction;286
9.3.7.2;Transcriptional Regulation of the Heat Shock Response;287
9.3.7.3;Chaperone Function in Normal and Disease States;288
9.3.7.4;Acknowledgements;291
9.3.7.5;References;291
9.3.8;Chapter 27: Hypoxia Mediated Signaling Pathways;296
9.3.8.1;Introduction;296
9.3.8.2;HIF Regulation;296
9.3.8.3;HIF Signaling and Metastasis;297
9.3.8.4;Unfolded Protein Response;298
9.3.8.5;Conclusions;299
9.3.8.6;References;299
9.3.9;Chapter 28: Regulation of mRNA Turnover by Cellular Stress;302
9.3.9.1;Introduction;302
9.3.9.2;RNA-Binding Proteins Controlling mRNA Turnover;302
9.3.9.3;mRNA Decay Determinants and Degradation Machineries;304
9.3.9.4;Stress-Activated Signaling Molecules that Regulate mRNA Turnover;305
9.3.9.5;Concluding Remarks;307
9.3.9.6;Acknowledgements;307
9.3.9.7;References;307
9.3.10;Chapter 29: Oncogenic Stress Responses;312
9.3.10.1;Introduction;312
9.3.10.2;Downstream Effectors of OIS;312
9.3.10.3;p38Mapk Signaling and OIS;314
9.3.10.4;DNA Damage Response and OIS;315
9.3.10.5;Concluding Remarks;316
9.3.10.6;References;316
9.3.11;Chapter 30: Ubiquitin and FANC Stress Responses;320
9.3.11.1;Introduction;320
9.3.11.2;Components of the Fanconi Anemia Pathway;320
9.3.11.3;The FA Core Complex and Activation of the FA Pathway;320
9.3.11.4;Mono-Ubiquitylation of FANCD2 and FANCI;322
9.3.11.5;Downstream Effectors and Interactions with other DNA Repair Proteins;323
9.3.11.6;De-Ubiquitylation of FANCD2 and FANCI;325
9.3.11.7;Non-Repair Functions of the FA Pathway;325
9.3.11.8;Conclusions;326
9.3.11.9;References;326
9.3.12;Chapter 31: Stress and .-H2AX;328
9.3.12.1;Introduction;328
9.3.12.2;Stress Induces DNA DSB Damage and .-H2AX Formation;328
9.3.12.3;Role Of . -H2AX In DNA Damage Repair Pathways;331
9.3.12.4;. -H2AX, a Marker to Monitor Cell Stress and a Protein Involved in Stress Signaling;333
9.3.12.5;Conclusions;334
9.3.12.6;Acknowledgements;334
9.3.12.7;References;334
10;Section C: Signaling to/from Intracellular Compartments;338
10.1;Chapter 32: Regulation of mRNA Turnover;340
10.1.1;Introduction;340
10.1.2;Current Model for MRNA Decay in Mammalian Cells;340
10.1.3;Deadenylation: The First Major Step Triggering mRNA Decay;341
10.1.4;Regulation of Deadenylation by a Protein that Interacts with Both Poly(A) Nuclease(S) and PABP;341
10.1.5;A Mechanism for Translationally Coupled mRNA Turnover;342
10.1.6;The Involvement of RNA Processing Bodies (P-Bodies) in Regulation of mRNA Turnover;342
10.1.7;Concluding Remarks;343
10.1.8;References;343
10.2;Chapter 33: Signaling to Cytoplasmic Polyadenylation and Translation;346
10.2.1;Introduction;346
10.2.2;The Biochemistry of Cytoplasmic Polyadenylation;346
10.2.3;Signaling to Polyadenylation;347
10.2.4;A Hierarchy of Translation Control;348
10.2.5;Polyadenylation in Mammalian Oocytes;348
10.2.6;Signaling to Polyadenylation in the Brain;348
10.2.7;Conclusions;348
10.2.8;References;349
10.3;Chapter 34: Translation Control and Insulin Signaling;352
10.3.1;Introduction;352
10.3.2;The Insulin Signaling Pathway;352
10.3.3;Insulin Signaling and Regulation of Translation Initiation;353
10.3.4;Insulin Signaling and Regulation of Translation Elongation;355
10.3.5;Insulin Signaling and Ribosome Biogenesis;355
10.3.6;Concluding Remarks;356
10.3.7;Acknowledgements;356
10.3.8;References;356
10.4;Chapter 35: Signaling Pathways that Mediate Translational Control of Ribosome Recruitment to mRNA;358
10.4.1;Introduction;358
10.4.2;Translation Initiation;358
10.4.3;The eIF4F Complex;359
10.4.4;Regulation of Translation Initiation by mTOR;359
10.4.5;Translation and Cancer;361
10.4.6;Conclusions;361
10.4.7;References;362
10.5;Chapter 36: Nuclear and Cytoplasmic Functions of Abl Tyrosine Kinase;366
10.5.1;Introduction;366
10.5.2;Functional Domains of ABL;366
10.5.3;Proteins that Interact with ABL;367
10.5.4;ABL in Signal Transduction;369
10.5.5;Future Prospects;371
10.5.6;Acknowledgement;371
10.5.7;References;371
10.6;Chapter 37: The SREBP Pathway: Gene Regulation through Sterol Sensing and Gated Protein Trafficking;374
10.6.1;SREBPS: Membrane Bound Transcription Factors;374
10.6.2;Scap: Sterol Sensor and Escorter of SREBP from ER to Golgi;375
10.6.3;Insig: Sterol Sensor and ER Retention Protein;376
10.6.4;Scap and Insig: Two Sensors for Two Classes of Sterols;377
10.6.5;Future Challenges;377
10.6.6;Acknowledgements;378
10.6.7;References;378
10.7;Chapter 38: Ubiquitination/Proteasome;380
10.7.1;Protein Degradation and the Ubiquitin/Proteasome System;380
10.7.2;Regulation of Ubiquitination by Substrate Modification;380
10.7.3;Regulation of Ubiquitin Ligase Activity;382
10.7.4;Processing of TFS by the Ubiquitin System;382
10.7.5;Modulation of Kinase Activity by Ubiquitination;383
10.7.6;Role of Ubiquitination/Proteasome in TF Activity;383
10.7.7;Conclusion;384
10.7.8;Acknowledgements;384
10.7.9;References;384
10.8;Chapter 39: Regulating Endoplasmic Reticulum Function through the Unfolded Protein Response;386
10.8.1;Introduction;386
10.8.2;Molecular Sensors;386
10.8.3;How Molecular Sensors Detect ER Stress;387
10.8.4;Downregulating the UPR;388
10.8.5;Cellular Effects of UPR Induction;389
10.8.6;Physiological UPR;393
10.8.7;Perspectives;396
10.8.8;References;396
10.9;Chapter 40: Protein Quality Control in the Endoplasmic Reticulum;402
10.9.1;Introduction;402
10.9.2;ER Quality Control;402
10.9.3;Unique Environment of the ER;402
10.9.4;Molecular Chaperones and Folding Enzyme;403
10.9.5;Disposal of Unfolded and Misfolded Protein;404
10.9.6;ER Subcompartments;405
10.9.7;References;405
10.10;Chapter 41: Protein Quality Control in Peroxisomes: Ubiquitination of the Peroxisomal Targeting Signal Receptors;408
10.10.1;Introduction;408
10.10.2;PTS (Co-) Receptor Ubiquitination: Conundrum and Confusion;409
10.10.3;S. Cerevisiae PEX18P is Degraded in an Ubiquitin Dependent Manner;409
10.10.4;S. Cerevisiae PEX5P, Two Distinct Ubiquitination Events, Two Distinct Functions;410
10.10.5;The Ubiquitination of P. Pastoris PEX20P: Two Independent Ubiquitination Events?;412
10.10.6;Involvement of the Ring Proteins in PTS (Co-) Receptor Ubiquitination;413
10.10.7;AAA Protein Mediated (Co-) Receptor Recycling: an Ubiquitin Dependent Event?;413
10.10.8;Conclusions;414
10.10.9;References;415
10.11;Chapter 42: Mitochondrial Dynamics: Fusion and Division;418
10.11.1;Introduction;418
10.11.2;Mitochondrial Fusion;418
10.11.3;Mitochondrial Division;419
10.11.4;Conclusions;420
10.11.5;Acknowledgements;420
10.11.6;References;420
10.12;Chapter 43: Signaling Pathways from Mitochondria to the Cytoplasm and Nucleus;424
10.12.1;Introduction;424
10.12.2;Small Molecules as Signals from Mitochondria;424
10.12.3;Small Cations: NA+, K+, MG+2, CA+2, H+;425
10.12.4;ATP, ADP, and 425
10.12.5;NADH and NAD+;426
10.12.6;Glutathione (GSH and GSSG);426
10.12.7;Reactive Oxygen Species;427
10.12.8;Iron Sulfur Clusters;428
10.12.9;Sirtuins;428
10.12.10;Mitochondrial Retrograde Signaling;428
10.12.11;Conclusion;430
10.12.12;References;430
10.13;Chapter 44: Quality Control and Quality Assurance in the Mitochondrion;432
10.13.1;Introduction;432
10.13.2;Quality Assurance Mediated by Chaperones and the Protein Translocation Complex;433
10.13.3;Quality Control of Protein Structure and Function Mediated by ATP Dependent Proteases;437
10.13.4;Perspective;439
10.13.5;Acknowledgements;439
10.13.6;References;439
10.14;Chapter 45: Mitochondria as Organizers of the Cellular Ca2+ Signaling Network;444
10.14.1;Introduction;444
10.14.2;Fundamentals;444
10.14.3;The Plasticity of the Mitochondrial Ca2+ Handling Machinery;445
10.14.4;Mitochondrial Ca2+ Handling in the Cellular Context;446
10.14.5;CODA;451
10.14.6;Acknowledgements;451
10.14.7;References;451
10.15;Chapter 46: Signaling during Organelle Division and Inheritance: Peroxisomes;454
10.15.1;Introduction to Peroxisomes;454
10.15.2;Peroxisome Division;455
10.15.3;Peroxisome Inheritance;456
10.15.4;Concluding Remarks;458
10.15.5;Acknowledgements;458
10.15.6;References;458
10.16;Chapter 47: Bidirectional Crosstalk between Actin Dynamics and Endocytosis;462
10.16.1;Introduction;462
10.16.2;From Actin to Endocytosis;462
10.16.3;Converging Molecular Machinery in Endocytosis and Actin Dynamics;465
10.16.4;From Endocytosis to Actin Dynamics;468
10.16.5;Outlook;468
10.16.6;Acknowledgements;469
10.16.7;References;469
10.17;Chapter 48: Signaling in Autophagy Related Pathways;474
10.17.1;Introduction;474
10.17.2;Signaling Control of Autophagy;474
10.17.3;Autophagy and Cell Death;476
10.17.4;Acknowledgements;477
10.17.5;References;477
11;Section D: Cell Cycle/Cell Death Signaling;480
11.1;Chapter 49: Regulation of Cell Cycle Progression;482
11.1.1;Introduction;482
11.1.2;Cyclins Define Cell Cycle Phase;482
11.1.3;Signals to Slow Progress: Regulation of CDKs by Inhibitory Proteins;485
11.1.4;CDKs are Positively and Negatively Regulated by Phosphorylation;485
11.1.5;Degradation: The Importance of Being Absent;486
11.1.6;Checkpoint Signaling;487
11.1.7;Lessons from Mice: Cell Division without CDKs;487
11.1.8;Knockout Mouse Models: Cycling without Cyclins;488
11.1.9;References;488
11.2;Chapter 50: The Role of Rac and Rho in Cell Cycle Progression;492
11.2.1;Introduction;492
11.2.2;Regulation of G1 Progression;492
11.2.3;The Function of RAC and RHO in Cell Cycle Progression and Transformation;493
11.2.4;Cell Cycle Targets of RAC and RHO;493
11.2.5;Future Perspectives;494
11.2.6;Acknowledgement;494
11.2.7;References;494
11.3;Chapter 51: The Role of Alternative Splicing During the Cell Cycle and Programmed Cell Death;496
11.3.1;Introduction;496
11.3.2;Apoptosis and Splicing;496
11.3.3;Cell Cycle and Splicing;497
11.3.4;Conclusions;498
11.3.5;References;499
11.4;Chapter 52: Cell-Cycle Functions and Regulation of Cdc14 Phosphatases;502
11.4.1;Introduction;502
11.4.2;The CDC14 Phosphatase Subgroup of PTPs;502
11.4.3;Budding Yeast CDC14 is Essential for Exit from Mitosis;503
11.4.4;Fission Yeast CDC14 Coordinates Cytokinesis with Mitosis;504
11.4.5;Potential Cell-Cycle Functions of Human CDC14A and B;504
11.4.6;References;505
11.5;Chapter 53: Caspases: Cell Signaling by Proteolysis;508
11.5.1;Protease Signaling;508
11.5.2;Apoptosis and Limited Proteolysis;508
11.5.3;Caspase Activation;509
11.5.4;Regulation by Inhibitors;510
11.5.5;References;511
11.6;Chapter 54: Apoptosis Signaling: A Means to an End;514
11.6.1;Introduction;514
11.6.2;The End of the Road;514
11.6.3;Caspase-8 Activation via Death Receptors;515
11.6.4;Mitochondria and the Activation of Caspase-9;517
11.6.5;Mitochondrial Outer Membrane Permeabilization;518
11.6.6;The BCL-2 Family;518
11.6.7;Cell Cycle Versus Apoptosis;520
11.6.8;Conclusions;520
11.6.9;References;520
11.7;Chapter 55: The Role of Ceramide in Cell Regulation;524
11.7.1;Introduction;524
11.7.2;Sphingolipid Metabolism;524
11.7.3;Apoptosis;525
11.7.4;Non-Apoptotic Ceramide Biology;529
11.7.5;Conclusions;529
11.7.6;References;530
12;Index;536