Article
Multidisciplinary Sciences
Stephanie L. Sarbanes, Vincent A. Blomen, Eric Lam, Soren Heissel, Joseph M. Luna, Thijn R. Brummelkamp, Erik Falck-Pedersen, H-Heinrich Hoffmann, Charles M. Rice
Summary: The journey of DNA viruses from the plasma membrane to the nuclear pore is crucial for viral replication, with MIB1 identified as a critical host factor for Adenovirus infectivity. MIB1's ubiquitination activity is essential for promoting AdV infection by potentially degrading negative regulators. This study highlights a new way that viruses exploit host cell machinery for replication, suggesting a potential target for therapeutic interventions against AdV infection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Gurusamy Hariharasudhan, Seo-Yeon Jeong, Min-Ji Kim, Sung Mi Jung, Gwanwoo Seo, Ju-Ran Moon, Sumi Lee, In-Youb Chang, Younghoon Kee, Ho Jin You, Jung-Hee Lee
Summary: SUMOylation of RAD51 is crucial for its recruitment to chromatin and HR repair. TOPORS-mediated RAD51 SUMOylation plays a key role in promoting HR repair and genomic maintenance.
NUCLEIC ACIDS RESEARCH
(2022)
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
Pragyesh Dixit, Swathi Shivaram Suratkal, Shrikant Babanrao Kokate, Debashish Chakraborty, Indrajit Poirah, Supriya Samal, Niranjan Rout, Shivaram P. Singh, Arup Sarkar, Asima Bhattacharyya
Summary: This study elucidates a novel mechanism of oxidative stress regulation by phosphorylated Siah2 in H. pylori-infected gastric epithelial cancer cells. Phosphorylation of Siah2 enhances the generation of reactive oxygen species (ROS) induced by H. pylori and leads to the degradation of the antioxidant protein GRP78. Surprisingly, cells expressing Siah2 with a phospho-null mutation have lower levels of cellular GRP78 but release more GRP78 and accumulate higher levels of ROS.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
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)
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)
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)
Article
Multidisciplinary Sciences
Xiaolan Liu, Xufeng Cen, Ronghai Wu, Ziyan Chen, Yanqi Xie, Fengqi Wang, Bing Shan, Linghui Zeng, Jichun Zhou, Bojian Xie, Yangjun Cai, Jinyan Huang, Yingjiqiong Liang, Youqian Wu, Chao Zhang, Dongrui Wang, Hongguang Xia
Summary: This study reveals that cisplatin enhances the anti-tumor effect of PD-L1 blockade and upregulates ARIH1 expression, promoting T cell infiltration and sensitizing tumors to immune checkpoint blockade. ARIH1 mediates activation of the STING pathway by ubiquitination and degradation of DNA-PKcs, which is a mechanism of tumor resistance to ICB. Activating ARIH1 is an effective strategy to improve the efficacy of cancer immunotherapy.
NATURE COMMUNICATIONS
(2023)
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.
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.
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.
Article
Biochemistry & Molecular Biology
Yi Zheng, Jian Deng, Lulu Han, Meng-Wei Zhuang, Yanwen Xu, Jing Zhang, Mei-Ling Nan, Yang Xiao, Peng Zhan, Xinyong Liu, Chengjiang Gao, Pei-Hui Wang
Summary: This study reveals the involvement of the stress response pathway and innate antiviral immunity in the pathogenic mechanism of SARS-CoV-2. NSP5 and N protein of SARS-CoV-2 were found to attenuate the formation of antiviral stress granules (avSG). NSP5 suppressed avSG formation and disrupted the RIG-I-MAVS complex to weaken the RIG-I-mediated antiviral response, while N protein specifically targeted cofactors upstream of RIG-I and affected the recognition of dsRNA by RIG-I.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
