Cullin-RING Ligases and Protein Neddylation

1. Front Matter

   Pages i-viii

   PDF

2. Introduction

   • Yi Sun

   Pages 1-8

3. Structural Biology of CRL Ubiquitin Ligases

   • Domnița-Valeria Rusnac, Ning Zheng

   Pages 9-31

4. Assembly and Regulation of CRL Ubiquitin Ligases

   • Kankan Wang, Raymond J. Deshaies, Xing Liu

   Pages 33-46

5. Cullin-RING Ligase Regulation by the COP9 Signalosome: Structural Mechanisms and New Physiologic Players

   • Feng Rao, Hong Lin, Yang Su

   Pages 47-60

6. Coordinated Actions Between p97 and Cullin-RING Ubiquitin Ligases for Protein Degradation

   • Wenbo Shi, Ran Ding, Pei Pei Zhou, Yuan Fang, Ruixi Wan, Yilin Chen et al.

   Pages 61-78

7. Regulation of Stem Cells by Cullin-RING Ligase

   • Lin Fu, Chun-Ping Cui, Lingqiang Zhang

   Pages 79-98

8. Viral Manipulations of the Cullin-RING Ubiquitin Ligases

   • Ying Liu, Xu Tan

   Pages 99-110

9. The Biology of F-box Proteins: The SCF Family of E3 Ubiquitin Ligases

   • Khai M. Nguyen, Luca Busino

   Pages 111-122

10. Targeting SCF E3 Ligases for Cancer Therapies

    • Jing Liu, Yunhua Peng, Jinfang Zhang, Jiangang Long, Jiankang Liu, Wenyi Wei

    Pages 123-146

11. Knockout Mouse Models Provide Insight into the Biological Functions of CRL1 Components

    • Tadashi Nakagawa, Keiko Nakayama, Keiichi I. Nakayama

    Pages 147-171

12. The Roles of Cullin-2 E3 Ubiquitin Ligase Complex in Cancer

    • Xijuan Liu, Giada Zurlo, Qing Zhang

    Pages 173-186

13. Cullin 3 and Its Role in Tumorigenesis

    • Ruey-Hwa Chen

    Pages 187-210

14. CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases

    • Pu Wang, Junbin Song, Dan Ye

    Pages 211-223

15. CRL4 Ubiquitin Pathway and DNA Damage Response

    • Pengbo Zhou, Fan Yan

    Pages 225-239

16. Cullin 4-DCAF Proteins in Tumorigenesis

    • Zhuan Zhou, Xinxin Song, Cindy M. Wavelet, Yong Wan

    Pages 241-259

17. Cullin RING Ligase 5 (CRL-5): Neddylation Activation and Biological Functions

    • Shizhen Zhang, Yi Sun

    Pages 261-283

18. Cullin-RING E3 Ubiquitin Ligase 7 in Growth Control and Cancer

    • Zhen-Qiang Pan

    Pages 285-296

19. Targeting Protein Neddylation for Cancer Therapy

    • Lisha Zhou, Lijun Jia

    Pages 297-315

20. Targeting Cullin-RING Ubiquitin Ligases and the Applications in PROTACs

    • Longyuan Gong, Danrui Cui, Xiufang Xiong, Yongchao Zhao

    Pages 317-347

This book summarizes all the important aspects of CRLs (Cullin-RING E3 Ubiquitin Ligases), while providing details of mechanistic specifics that go beyond protein ubiquitination and neddylation. Ubiquitin ligases, including the CRLs, which are activated by neddylation, play an important role in diverse biological processes and are involved in various human diseases, particularly cancer. The book covers various topics, such as CRL structure, biology, genetics, its regulation by neddylation, its pivotal role in human disease, and its potential in drug discovery and targeted therapies. The book appeals to biochemists and biologists working in other fields, and, given the importance of CRLs in all aspects of cell biology and the great promise of targeting these complexes for therapy, is a valuable resource anyone interested in modern biology or medicine.

• Cullin-RING ligases
• protein neddylation
• protein ubiquitylation
• protein degradation
• targeted therapy
• CRLs

• Radiation Oncology, University of Michigan, Ann Arbor, USA

  Yi Sun

• Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA

  Wenyi Wei

• Life Science Institute, Zhejiang University, Hangzhou, China

  Jianping Jin

Dr. Yi Sun completed his medical training in China in the early 1980s, his Ph.D. at the University of Iowa, USA, in 1989, and his postdoctorate at the NCI. Currently, he is a Lawrence-Krause Research Professor of Radiation Oncology, and Director of the Division of Radiation & Cancer Biology, Department of Radiation Oncology at the University of Michigan. His main research aims are validating SAG-Cullin RING Ligase (CRL) and neddylation as cancer targets, and identifying small molecule inhibitors against these targets for anticancer therapy. Dr. Sun is the author of 222 peer- reviewed articles published in various prestigious journals, including Dev Cell, eLife, J Cell Biol, J Clin Invest,Mol Cell,Nature Communications, PNAS, and Cancer Res. He serves as editorial board member of several scientific journals.  He was elected as a fellow of the AAAS (American Association for the Advancement of Science) in 2012. 

Dr. Wenyi Wei received his B.A. degree from Shandong University in 1993 and pursued his M.S. at the Chinese Academy of Science from 1993 to 1996. Afterwards, Dr. Wei completed his Ph.D. at the MCB department at Brown University and his postdoctorate at the laboratory of Dr. William Kaelin, Jr. at DFCI, Harvard Medical School. In 2006, Dr. Wei moved to the Department Pathology at Beth Israel Deaconess Medical Center, Harvard Medical School, where his research focuses on understanding how aberrant cell signaling events contribute to cell cycle dysregulation and subsequent tumorigenesis, to provide the molecular basis and the rationale to develop novel anti-cancer therapies targeting specific cell signaling pathways. 

Dr. Jianping Jin completed his PhD at Texas A&M University at College Station in 2000, and his postdoctorate in Dr. J Wade Harper’s Laboratory at Baylor College of Medicine and then at Harvard Medical School. Currently, he is a Professor and senior investigatorat the Life Science Institute, Zhejiang University, China. His main research projects focus on the ubiquitin signaling pathway, and its roles in cancer and inflammation. He discovered Uba6, the second ubiquitin E1 gene (humans only have two ubiquitin E1 genes), and its specific E2 gene, Use1 (also called Ube2Z). He was among the first to identify the family of DCAF genes, which are substarte adaptors of the Cullin4 ubiquitin ligases. Dr. Jin has published more than 50 peer-reviewed articles, and serves as an editorial member of the Journal of Biological Chemistry. He was a co-organizer for three Cold Spring Harbor Asia meetings on the ubiquitin family.

Policies and ethics