Article
Chemistry, Multidisciplinary
Lu-Jun Liang, Guo-Chao Chu, Qian Qu, Chong Zuo, Junxiong Mao, Qingyun Zheng, Jingnan Chen, Xianbin Meng, Yangwode Jing, Haiteng Deng, Yi-Ming Li, Lei Liu
Summary: This study describes a new total chemical synthesis approach for constructing a structurally new activity-based E2-Ub probe, which covalently captures the catalytic site of Cys-dependent E3 ligases. Chemical cross-linking coupled with mass spectrometry demonstrated the utility of this new probe in structural analysis of intermediates formed during thiol transfer processes. The study exemplifies the utility of chemical protein synthesis in developing protein probes for biological studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Lingmin Yuan, Zongyang Lv, Melanie J. Adams, Shaun K. Olsen
Summary: By determining the structure of a covalently trapped E1-E2-ubiquitin thioester mimetic, researchers identified two distinct conformations of the E1-E2-Ub complex which suggest the presence of an affinity switch mechanism facilitating thioester transfer.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Kaeli A. Welsh, Derek L. Bolhuis, Anneroos E. Nederstigt, Joshua Boyer, Brenda R. S. Temple, Thomas Bonacci, Li Gu, Alban Ordureau, J. Wade Harper, Joshua P. Steimel, Qi Zhang, Michael J. Emanuele, Joseph S. Harrison, Nicholas G. Brown
Summary: Polyubiquitination mediated by E2 and E3 enzymes is essential for cell cycle control, epigenetic regulation, and development. The helix-turn-helix (HTH) motif of the UBC has been shown to regulate the intrinsic polyubiquitination activity in different E2s, with distinct functions observed in UBE2S and UBE2R2. The repurposing of the E2(HTH) motif in these proteins suggests a new mechanism for modulating ubiquitin transfer and highlights the potential for additional regulation in E2-E3-mediated polyubiquitination.
Review
Biochemistry & Molecular Biology
Yu Meng, Huiyan Sun, Yayun Li, Shuang Zhao, Juan Su, Furong Zeng, Guangtong Deng, Xiang Chen
Summary: Ferroptosis is regulated by ubiquitination at post-translational level, in which E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) play crucial roles. The dysregulation of ubiquitin system enzymes contributes to the progression of multiple cancers. Understanding the regulatory networks of ferroptosis mediated by E3s or DUBs may provide new opportunities for cancer therapy.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biology
Dawafuti Sherpa, Judith Mueller, Oezge Karayel, Peng Xu, Yu Yao, Jakub Chrustowicz, Karthik Gottemukkala, Christine Baumann, Annette Gross, Oliver Czarnecki, Wei Zhang, Jun Gu, Johan Nilvebrant, Sachdev S. Sidhu, Peter J. Murray, Matthias Mann, Mitchell J. Weiss, Brenda A. Schulman, Arno F. Alpi
Summary: This study measured the proteomic landscape of in vitro human erythropoiesis models and found dynamic differential expression of subunits of the CTLH E3 ubiquitin ligase complex, as well as changes in the protein abundance of UBE2H. Inactivation of CTLH E3 assemblies or UBE2H led to defects in erythroid progenitors, including accelerated maturation and inefficient enucleation. These findings suggest that dynamic changes in UBE2H-CTLH E2-E3 modules control the orderly progression of human erythropoiesis.
Article
Biochemistry & Molecular Biology
Kazuhide Miyamoto, Atsushi Matsumoto
Summary: In this study, the unique properties of ARFs in E2-binding and auto-ubiquitination were demonstrated in ubiquitination assays. Point mutations of ARF by tryptophan resulted in changes in E2 specificity and Ub chain elongation. ARF mutants interacted with all 11 E2s and promoted auto-ubiquitination, allowing specific detection of E2 activities during ubiquitination.
Review
Biochemistry & Molecular Biology
Shu-Chun Chang, Bo-Xiang Zhang, Jeak Ling Ding
Summary: The ubiquitin-proteasome system plays a crucial role in modulating carcinogenesis by ubiquitination of cancer-related target proteins. Specific E2-E3 pairings are key in cancer progression, and current research focuses on E2-E3 interface motifs and the influence of UBE2O on E2-E3 pairing. The development of anti-cancer drugs targeting E2-E3 interacting residues for precision in cancer treatment is being carefully considered.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Biochemistry & Molecular Biology
Keerthiraju E. Ravichandran, Lars Kaduhr, Bozena Skupien-Rabian, Ekaterina Shvetsova, Mikolaj Sokolowski, Roscislaw Krutyholowa, Dominika Kwasna, Cindy Brachmann, Sean Lin, Sebastian Guzman Perez, Piotr Wilk, Manuel Kosters, Przemyslaw Grudnik, Urszula Jankowska, Sebastian A. Leidel, Raffael Schaffrath, Sebastian Glatt
Summary: This study investigated the covalent attachment of Urm1 to cellular target proteins, revealing that this process is independent of E2/E3 and requires oxidative stress, different from other UBLs. It was also found that urmylation is accompanied by the transfer of sulfur to cysteine residues in target proteins, a process known as cysteine persulfidation, highlighting the role of the Uba4-Urm1 system as an evolutionary link between prokaryotic SCPs and UBL modifications in modern eukaryotes.
Article
Multidisciplinary Sciences
Xiao-Wen Zhang, Na Feng, Yan-Chen Liu, Qiang Guo, Jing-Kang Wang, Yi-Zhen Bai, Xiao-Ming Ye, Zhuo Yang, Heng Yang, Yang Liu, Mi-Mi Yang, Yan-Hang Wang, Xiao-Meng Shi, Dan Liu, Peng-Fei Tu, Ke-Wu Zeng
Summary: This study discovers a natural small molecule called eupalinolide B (EB) that inhibits USP7 to alleviate symptoms of neurodegenerative diseases. EB selectively modifies the Cys(576) site, inhibiting the activity of USP7 and causing the degradation of Keap1. This leads to the activation of anti-neuroinflammation genes in microglia. The effectiveness of this treatment method is validated in mouse models.
Review
Pharmacology & Pharmacy
Wenya Bai, Siying Huo, Junjie Li, Jianlin Shao
Summary: This paper provides an overview of the advances in ubiquitination research, the structure and function of A20, and the relationships between A20 and immune inflammatory response, apoptosis, necroptosis, pyroptosis, and autophagy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Qiong Wu, Jingru Yin, Min Jiang, Jingyu Zhang, Zhenghong Sui
Summary: This study identified and classified E2 and E3 genes in Gracilariopsis lemaneiformis, an economically important red alga, and analyzed their expression levels and functions during tetrasporophyte development. The results suggest that certain genes may play a crucial role in the fertility of this alga.
Article
Biology
Sara Scinicariello, Adrian Soderholm, Markus Schaefer, Alexandra Shulkina, Irene Schwartz, Kathrin Hacker, Rebeca Gogova, Robert Kalis, Kimon Froussios, Valentina Budroni, Annika Bestehorn, Tim Clausen, Pavel Kovarik, Johannes Zuber, Gijs A. Versteeg
Summary: Tristetraprolin (TTP) stability is controlled by factors including lysine-ubiquitination and phosphorylation. The E3 ligase HUWE1 was identified as a regulator of TTP stability, indirectly controlling its phosphorylation. This study provides new insights into the regulation of TTP and its impact on immune response.
Article
Multidisciplinary Sciences
Zhibin Lin, Peijun Yang, Yufeng Hu, Hao Xu, Juanli Duan, Fei He, Kefeng Dou, Lin Wang
Summary: This study reveals the important role of RNF13 protein in NAFLD progression, which can alleviate NAFLD phenotypes by facilitating TRIM29-mediated degradation of STING.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Yijun Yu, Sheng Zhao, Deao Gu, Bijun Zhu, Hanxiao Liu, Wenlei Wu, Jiangjiexing Wu, Hui Wei, Leiying Miao
Summary: This study introduces a therapeutic approach for managing periodontitis using cerium oxide nanoparticles. The synthesized nanoparticles can scavenge reactive oxygen species, suppress inflammation reactions, and improve tissue restoration. The findings highlight the potential of cerium oxide nanoparticles for treating periodontitis and provide valuable insights into the application of nanozymes in inflammatory diseases.
Article
Cell Biology
Lijie Yao, Liqing Xu, Lijuan Zhou, Shuizhen Wu, Weihao Zou, Min Chen, Jiating Chen, Hongjuan Peng
Summary: Toxoplasma gondii evades host innate immune responses by promoting the degradation of TRIM21 through interacting with its virulence factor ROP18, TRIM21 plays a significant role in combating T. gondii infection, and its function can modulate parasitophorous vacuole membrane acidification through ubiquitin labeling, affecting the parasite's growth.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)