MARCUS GROETTRUP is a Professor for Immunology in the Department of Biology of Konstanz University in Germany. His main interests are in the role of the immunoproteasome in antigen fragmentation and autoimmunity. Moreover, he has studied the function and conjugation of the ubiquitin-like protein FAT10. He studied biochemistry in Tübingen and ET H Zürich and did his diploma thesis in the laboratory of H. Hengartner and R. Zinkernagel. During his PhD at the Basel Institute for Immunology with H. von Boehmer he discovered the pre T cell receptor. After habilitation at Humboldt University Berlin in the group of P-M. Kloetzel on the topic of antigen processing he founded his own group at the Cantonal Hospital St. Gallen, Switzerland. Since 2002 he holds the Chair of Immunology at the University of Konstanz, Germany. Several prizes were awarded to Dr. Groettrup like the Award of the Sandoz Foundation for Therapeutic Research, the Karl Lohmann Prize of the German Society for Biological Chemistry, the Langener Science Prize of the Paul Ehrlich Institute, and the Research Award by the CaP CURE foundation.

Inhaltsverzeichnis

Preface: New Paradigms in the Conjugation of Ubiquitin Family Modifiers xvii Marcus Groettrup 1. Activation of Ubiquitin and Ubiquitin?Like Proteins 1 Frederick C. Streich, Jr. and Arthur L. Haas 2. Control of Ubiquitin Conjugation by Cdc48 and Its Cofactors 17 Alexander Buchberger 3. Regulation of Ubiquitin Receptors by Coupled Monoubiquitination 31 Daniela Hoeller and Ivan Dikic 4. Control of Cullin?Ring Ubiquitin Ligase Activity by Nedd8 41 Raymond J. Deshaies, Ethan D. Emberley and Anjanabha Saha 5. Control of Deneddylation by the Cop9 Signalosome 57 Tilo Schmaler and Wolfgang Dubiel 6. Mechanism, Specificity and Structure of the Deubiquitinases 69 David Komander 7. Ubiquitin Conjugation and Deconjugation in NF?kB Signaling 88 Michael Düwel, Kamyar Hadian and Daniel Krappmann 8. Functions of Linear Ubiquitin Chains in the NF?kB Pathway: Linear Polyubiquitin in NF??B Signaling 100 Kazuhiro Iwai 9. Assembly of K11?Linked Ubiquitin Chains by the Anaphase?Promoting Complex 107 Michael Rape 10. Ubiquitin Family Members in the Regulation of the Tumor Suppressor p53 116 Dimitris P. Xirodimas and Martin Scheffner 11. Ubiquitylation in the ERAD Pathway 136 Frederik Eisele, Antje Schäfer and Dieter H. Wolf 12. Pupylation: A Signal for Proteasomal Degradation in Mycobacterium tuberculosis 149 Kristin E. Burns and K. Heran Darwin 13. sumo Control 158 Katharina Maderböck and Andrea Pichler 14. The In Vivo Functions of Desumoylating Enzymes 170 Tasneem Bawa?Khalfe and Edward T.H. Yeh 15. Regulatory Functions of Ubiquitin and Sumo in DNA Repair Pathways 184 Stefan Jentsch and Stefan Müller 16. Sumoylation as a Signal for Polyubiquitylation and Proteasomal Degradation 195 Maria Miteva, Kirstin Keusekotten, Kay Hofmann, Gerrit J.K. Praefcke and R. Jürgen Dohmen 17. In Vivo Functions of Isgylation 215 Klaus?Peter Knobeloch 18. Identification and Validation of ISG15 Target Proteins 228 Larissa A. Durfee and Jon M. Huibregtse 19. FAT 10: Activated by UBA6and Functioning in Protein Degradation 238 Christiane Pelzer and Marcus Groettrup Index 247

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+ 1 a a 4 + 17 10 15 ubiquitin; and of 16 VCP 17 18 20 33 34 34 36 p domain. 41 42 42 43 P U 42 47 binding. C. elegans 16 In 21 22 50 51 52 53 13 and UFD 4 10 of Cdc48. 18 30 of Ufd2. COFACTORS 47 23 13 47 47 47 72 15 15 and of Spt23 p90. Ufd2 and Cdc48. In C. elegans 74 16 75 75 76 76 Ufd2 25 54 54 7 56 p47 7 7 80 30 30 81 82 82 but and CD3 26 DUB COFACTORS 30 UFD3 OTU1 4 Cdc48 30 4 OLE1. 15 27 87 REFERENCES 30 REGULATION OF UBIQUITIN MONOUBIQUITINATION UBIQUITINATION 1 32 7 S) d 33 12 13 14 15 18 19 15 20 21 35 15 15 27 15 31 32 31 33 36 monoubiquitination of pol pol 34 37 34 monoubiquitination. 20 35 trans 3 15 REFERENCES by monoubiquitination. Mol Cell; 2009. UBIQUITIN LIGASE ACTIVITY BY Nedd 1 2 of 41 5 6 8 fold. 9 13 14 edd 43 18 18 K M and k 18 22 23 K M 24 25 K M 26 edd 45 18 27 K M K D 18 25 . 8 10 M 21 28 MECHANISM AND REGULATION OF CRLs 34 41 34 edd 47 48 S. pombe 49 51 p27 and I by SCF and SCF 57 58 59 60 CTD CTD CTD CTD in Cul5 CTD CTD CTD 60 18

Focussed on the modifiers ubiquitin, SUMO1/2/3, NED 8, ISG15 and FAT10 Discusses how conjugation enzymes determine specific linkages and how they are interpreted by ubiquitin binding domains Cross-talk between the ubiquitin family modification systems