Article
Cell Biology
Tingting Gan, Yuhong Wang, Yang Liu, David G. Schatz, Jiazhi Hu
Summary: RAG1 and RAG2 form a tetramer nuclease for V(D)J recombination in lymphocytes, with RAG1 requiring interaction with RAG2 to be activated. RAG2 disrupts RAG1 aggregates, activating recombination.
Article
Biochemistry & Molecular Biology
Doris Niewolik, Klaus Schwarz
Summary: The interaction between nuclease ARTEMIS and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a crucial role in the repair of DNA double strand breaks and V(D)J recombination activity. Mutations disrupting this interaction have been found to impair the function of these proteins. Small fragments capable of mediating this interaction have been identified, offering possibilities for the design of specific inhibitors.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Plant Sciences
Jinhao Sun, Cuiling Yuan, Meng Wang, Anming Ding, Guohua Chai, Yuhe Sun, Gongke Zhou, Dahai Yang, Yingzhen Kong
Summary: In this study, the regulatory mechanisms of pectin demethylesterification were investigated, revealing that the mud1 Arabidopsis mutant has increased mucilage adherence due to increased PMEs activities and decreased DM. It was suggested that MUD1 may act as an ubiquitin ligase to regulate the DM of pectin by post-transcriptionally removing proteins that negatively regulate PMEs in seed coat mucilage.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Orsolya Bilkei-Gorzo, Tiaan Heunis, Jose Luis Marin-Rubio, Francesca Romana Cianfanelli, Benjamin Bernard Armando Raymond, Joseph Inns, Daniela Fabrikova, Julien Peltier, Fiona Oakley, Ralf Schmid, Anetta Hartlova, Matthias Trost
Summary: This study reveals the importance of phagosomal ubiquitylation and the E3 ubiquitin ligase RNF115 in regulating innate immune functions during bacterial infections.
Article
Biochemistry & Molecular Biology
Lu Gong, Samuel Bates, Yujun Li, Xin Lin, Wenyi Wei, Xiaobo Zhou
Summary: Research found that SNPs within the FAM13A gene are significantly associated with chronic obstructive pulmonary disease and lung function. After treatment with cigarette smoke extract, FAM13A protein is phosphorylated at the serine 312 residue by AKT kinase and recognized by the CULLIN4A/DCAF1 E3 ligase complex, leading to its ubiquitination-mediated degradation. Additionally, AKT activation also leads to downregulation of FAM13A protein levels in mice with influenza or naphthalene-induced lung injury. Functionally, reduced FAM13A protein levels accelerate epithelial cell proliferation in murine lungs during the recovery phase after injury.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Medicinal
Adam G. Bond, Conner Craigon, Kwok-Ho Chan, Andrea Testa, Athanasios Karapetsas, Rotimi Fasimoye, Thomas Macartney, J. Julian Blow, Dario R. Alessi, Alessio Ciulli
Summary: This study describes the design and development of a new protein degradation system utilizing a variant of the Brd4 bromodomain as a degradation tag. The system effectively degrades BromoTagged proteins in a fast, selective manner, showing favorable pharmacokinetic profile in mice. This system expands the arsenal of chemical genetic degradation tools for manipulating protein levels and exploring therapeutic potential in cells and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Martin P. Schwalm, Lena M. Berger, Maximilian N. Meuter, James D. Vasta, Cesear R. Corona, Sandra Roehm, Benedict-Tilman Berger, Frederic Farges, Sebastian M. Beinert, Franziska Preuss, Viktoria Morasch, Vladimir V. Rogov, Sebastian Mathea, Krishna Saxena, Matthew B. Robers, Susanne Mueller, Stefan Knapp
Summary: E3 ligases play a crucial role in regulating protein homeostasis by recruiting substrate proteins to the proteasomal degradation machinery. Recent research has focused on the Baculovirus IAP Repeat (BIR) family of E3 ligases, which contain a structurally conserved but diverse protein interaction domain. The Inhibitors of Apoptosis (IAP) family, which typically have three BIR domains, are promising drug targets. However, there is currently a lack of assay tools to evaluate the selectivity of inhibitors in this target area.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Rupa Kumari, Urbi Roy, Sagar Desai, Namrata M. Nilavar, Annemarie Van Nieuwenhuijze, Amita Paranjape, Gudapureddy Radha, Pushpinder Bawa, Mrinal Srivastava, Mridula Nambiar, Kithiganahalli Narayanaswamy Balaji, Adrian Liston, Bibha Choudhary, Sathees C. Raghavan
Summary: The study showed that miR-29c regulates RAG1 in a B cell stage-specific manner, modulation of miR-29c levels affects V(D)J recombination efficiency in pre-B cells, and a negative correlation between miR-29c and RAG1 levels is observed in different developmental stages.
Review
Biochemistry & Molecular Biology
Rui Zhang, Shaoqing Shi
Summary: HECT-type E3 ubiquitin ligases play a vital role in controlling protein function and stability, and members of the NEDD4 family have critical roles in dysregulation of autophagy in cancer cells. This review focuses on the role of NEDD4 E3 ligases in defective autophagy in cancer cells, discussing their function, substrates, and signaling pathways, providing a basis for cancer treatment through modulation of these ligases.
MOLECULAR MEDICINE
(2023)
Review
Immunology
Haoran Cui, Yaxian Zhang, Leiliang Zhang
Summary: Poxviruses have evolved various mechanisms to evade innate immunity, some of which involve poxvirus-encoded E3 ubiquitin ligases and adaptor proteins. These proteins can be categorized into five groups based on their functional domains and ubiquitin transfer mechanisms. Most known substrates of poxvirus E3 ubiquitin ligases are components of the innate immune system. Current research progress provides mechanistic insights into the interaction between these viruses and their hosts.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Helen A. Beilinson, Rebecca A. Glynn, Anurupa Devi Yadavalli, Jianxiong Xiao, Elizabeth Corbett, Huseyin Saribasak, Rahul Arya, Charline Miot, Anamika Bhattacharyya, Jessica M. Jones, Jagan M. R. Pongubala, Craig H. Bassing, David G. Schatz
Summary: The RAG1 N-terminal region regulates V(D)J recombination and lymphocyte development through multiple pathways, including control of the balance between short- and long-range recombination, as shown in studies with different RAG1 mutant mice.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Plant Sciences
Jialing Zhang, Chaonan Li, Long Li, Yajun Xi, Jingyi Wang, Xinguo Mao, Ruilian Jing
Summary: TaAIRP2-1B regulates spike length by facilitating TaHIPP3 degradation, and the haplotype Hap-1B-1 of TaAIRP2-1B is a favorable natural variation for increasing spike length in wheat. This study provides insights into the role of E3 ubiquitin ligase genes in wheat development and identifies TaAIRP2-1B as a key regulator of spike length. The findings also offer genetic resources and markers for wheat molecular breeding.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Review
Biochemistry & Molecular Biology
Ishita Tripathi-Giesgen, Christian Behrends, Arno F. Alpi
Summary: The ubiquitin system plays a crucial role in the host cellular defense program against bacterial infection, especially when certain bacteria are exposed to the host cytosol during invasion. Host cell E3 ubiquitin ligases contribute to the formation of a protective ubiquitin coat on invading pathogens, with their divergent ubiquitin conjugation mechanisms influencing the complexity of the anti-bacterial coating. Bacteria have evolved strategies to evade the activities of the host ubiquitin system.
Review
Biochemistry & Molecular Biology
Dong Wang, Yuanming Zou, Xinyue Huang, Zeyu Yin, Mohan Li, Jiaqi Xu, Boquan Wu, Da Li, Ying Zhang, Yingxian Sun, Xingang Zhang, Naijin Zhang
Summary: The ubiquitin-proteasome system is crucial for regulating protein levels in cells, and SMURF1 and SMURF2 are important components that maintain physiological processes by regulating the stability of multiple proteins. The regulatory functions of SMURFs in disease progression are complex, either facilitative or inhibitory, and understanding their mechanisms offers potential therapeutic targets and new avenues for research.
Review
Biochemistry & Molecular Biology
Dong Wang, Yuanming Zou, Xinyue Huang, Zeyu Yin, Mohan Li, Jiaqi Xu, Boquan Wu, Da Li, Ying Zhang, Yingxian Sun, Xingang Zhang, Naijin Zhang
Summary: The ubiquitin-proteasome system plays a crucial role in regulating protein levels in cells. SMURF1 and SMURF2 are key components in this system, responsible for regulating protein stability and maintaining physiological processes such as cell migration, proliferation, and apoptosis. They also play significant roles in disease progression, with complex regulatory functions. This review focuses on the mechanisms by which SMURF1 and SMURF2 regulate disease progression in non-cancerous diseases, providing potential therapeutic targets for various diseases and new research avenues for SMURF proteins.