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)
Review
Pharmacology & Pharmacy
Sunil Singh, Joel Ng, J. Sivaraman
Summary: The HECT E3 ligase family consists of three sub-families: NEDD4, HERC, and Other, with the latter being less explored. Members of the Other subfamily have diverse N-terminal regions preceding the conserved HECT domains, which influence the stability and activity of the proteins. They assemble atypical ubiquitin linkages and cooperate with E3 ligases from other subfamilies to form branched ubiquitin chains on substrates, making them potential candidates for therapeutic drug development.
PHARMACOLOGY & THERAPEUTICS
(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.
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
Oncology
Min Sup Song, Pier Paolo Pandolfi
Summary: Members of the HECT family of E3 ubiquitin ligases have significant regulatory roles in PTEN function, subcellular localization, and levels, enabling the identification of genes involved in tumorigenesis and cancer susceptibility. These findings hold promise for the development of novel therapeutic approaches for cancer prevention and treatment, as well as other diseases.
SEMINARS IN CANCER BIOLOGY
(2022)
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)
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)
Review
Biochemistry & Molecular Biology
Jun Goto, Yoichiro Otaki, Tetsu Watanabe, Masafumi Watanabe
Summary: Despite medical advances, cardiac disease remains a significant health issue with high mortality rates. Maladaptive cardiac remodeling, like hypertrophy and fibrosis, is a risk factor for heart failure, underscoring the important role of ubiquitylation in cardiac disease development. HECT-type E3 ligases play a crucial role in ubiquitylation and have been implicated in a wide range of human diseases, including cardiac diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Katarzyna Retzer, Jeanette Moulinier-Anzola, Rebecca Lugsteiner, Nataliia Konstantinova, Maximilian Schwihla, Barbara Korbei, Christian Luschnig
Summary: Intracellular sorting and abundance of plasma membrane proteins are crucial for plants to sense and respond to environmental inputs. The reversible covalent modification by ubiquitin plays a key role in inducing adjustments in protein localization and functionality. The RING DOMAIN LIGASE family, including RGLG1, has been implicated in endocytic vacuolar cargo sorting, and this study provides evidence for their role in cargo trafficking between plasma membrane and endosomal compartments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Helge M. Magnussen, Danny T. Huang
Summary: The research compared the purification profiles of the MDM2 RING domain from various species and found that the RING domain from other species is less prone to aggregation compared to human. A single point mutation, G443T, was identified to greatly enhance the dimeric fraction of human MDM2 RING domain during purification, which will facilitate further studies and the development of new anti-cancer drugs.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
David C. Hughes, Leslie M. Baehr, David S. Waddell, Adam P. Sharples, Sue C. Bodine
Summary: The development and prevalence of diseases associated with aging have a global health burden on society. One hallmark of aging is the loss of proteostasis, partly caused by alterations to the ubiquitin-proteasome system and lysosome-autophagy system, leading to impaired function and maintenance of mass in tissues such as skeletal muscle. In skeletal muscle, functional impairment occurs early in the aging process and depends on proteostatic mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Andrew G. Manford, Elijah L. Mena, Karen Y. Shih, Christine L. Gee, Rachael McMinimy, Brenda Martinez-Gonzalez, Rumi Sherriff, Brandon Lew, Madeline Zoltek, Fernando Rodriguez-Perez, Makda Woldesenbet, John Kuriyan, Michael Rape
Summary: Oxidative phosphorylation not only produces ATP, but also generates reactive oxygen species. Cells alleviate reductive stress by ubiquitylating and degrading FNIP1, which relies on zinc as a molecular glue during this process.
Article
Multidisciplinary Sciences
Terry R. Suk, Marilyn T. Tirard, Zoe A. Fisk, Miso Mitkovski, Haley M. Geertsma, Jean-Louis A. Parmasad, Meghan M. Heer, Steve M. Callaghan, Fritz Benseler, Nils Brose, Marilyn Tirard, Maxime W. C. Rousseaux
Summary: SUMOylation is a protein modification widely present in evolutionarily conserved eukaryotes and has broad biological significance. To differentiate between SUMO paralogs and uncover their specific functions in vivo, His6-HA-Sumo2 and HA-Sumo2 knockin mouse lines were generated, expanding upon the existing His6-HA-Sumo1 mouse line. By utilizing the specificity of the HA epitope, regional differences in Sumo1 and Sumo2 expression were observed through whole-brain imaging. Immunoprecipitation coupled with mass spectrometry identified shared and specific neuronal targets of Sumo1 and Sumo2, and proximity ligation assays provided insight into the subcellular distribution of neuronal Sumo2-conjugates. These mouse models and associated datasets provide a powerful framework to determine the native SUMO code in cells of the central nervous system.
Article
Biochemistry & Molecular Biology
Virginia De Cesare
Summary: Ubiquitination, the attachment of ubiquitin to a substrate, plays a critical role in regulating the lifetime and function of cellular components. This process is mediated by enzymes including E1 activating enzyme, E2 conjugating enzymes, E3 ligases, and DUBs deubiquitylating enzymes. Understanding the function and specificity of ubiquitin machinery is of great importance due to its involvement in various cellular processes.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Yawei Ru, Xiaojie Yan, Bing Zhang, Lili Song, Qiqi Feng, Chen Ye, Zhili Zhou, Zhenzhen Yang, Yao Li, Zhenjian Zhang, Qianqian Li, Wenyi Mi, Cheng Dong
Summary: In this study, a new C-degron pathway, called the Gln/C-degron pathway, was discovered. The B30.2 domain of TRIM7 mediates the recognition of proteins with a C-terminal glutamine. The C-terminal residues of the substrate play a crucial role in C-degron recognition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)