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
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
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
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.
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)
Article
Chemistry, Multidisciplinary
Xiyun Ye, Peiyuan Zhang, Jason Tao, John C. K. Wang, Amirhossein Mafi, Nathalie M. Grob, Anthony J. Quartararo, Hannah T. Baddock, Leanne J. G. Chan, Fiona E. McAllister, Ian Foe, Andrei Loas, Dan L. Eaton, Qi Hao, Aaron H. Nile, Bradley L. Pentelute
Summary: In this study, a covalent peptide inhibitor called reactide was designed to inhibit HPV-mediated degradation of p53 by targeting cysteine 58 in HPV16 E6. This reactide provides a starting point for the development of covalent peptidomimetic inhibitors against HPV-driven cancers.
Article
Immunology
Wilbert Mbuya, Kathrin Held, Ruby D. Mcharo, Antelmo Haule, Jacklina Mhizde, Jonathan Mnkai, Anifrid Mahenge, Maria Mwakatima, Margareth Sembo, Wolfram Mwalongo, Peter Agrea, Michael Hoelscher, Leonard Maboko, Elmar Saathoff, Otto Geisenberger, France Rwegoshora, Liset Torres, Richard A. Koup, Arne Kroidl, Mkunde Chachage, Christof Geldmacher
Summary: The study observed that HPV oncoprotein-specific T-cell responses were reduced in women with HIV infection, precancerous lesions, and low CD4 T-cell counts. This depletion of T-cell responses may contribute to the increased risk of HPV persistence and cancerogenesis in women living with HIV. Furthermore, HPV16 infections may have exceptional potential for cancerogenesis due to their low inherent immunogenicity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Qian Lv, Liqun Li, Ying Meng, Huimin Sun, Liuping Chen, Bingxin Wang, Xuejun Li
Summary: The study revealed that TaGW2-6A interacts with TaAGPS and degrades TaAGPS through the 26S proteasome pathway, influencing seed size. This mechanism provides new insights into the formation of wheat grain weight.
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)
Review
Immunology
Yiyang Liu, Lu Jiang, Xuemeng Sun, Yixuan Song, Yihan Liu, Leiliang Zhang
Summary: TRIM7 plays significant roles in host defense against viral infections and immune signaling pathways. However, viruses have developed immune evasion mechanisms to counteract its function. Understanding the interaction between TRIM7 and antiviral immunity is crucial for developing innovative treatments for viral diseases.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Biology
Osamu Nakabayashi, Hirotaka Takahashi, Kenta Moriwaki, Sachiko Komazawa-Sakon, Fumiaki Ohtake, Shin Murai, Yuichi Tsuchiya, Yuki Koyahara, Yasushi Saeki, Yukiko Yoshida, Soh Yamazaki, Fuminori Tokunaga, Tatsuya Sawasaki, Hiroyasu Nakano
Summary: The E3 ligase MIB2 ubiquitylates apoptosis-inhibitor cFLIP, suppressing RIPK1 kinase activity-dependent and -independent apoptosis. Deletion of MIB2 enhances RIPK1 kinase activity and impairs ubiquitylation of cFLIP(L), resulting in increased apoptosis.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Takashi Imada, Takeshi Shimi, Ai Kaiho, Yasushi Saeki, Hiroshi Kimura
Summary: In eukaryotic nuclei, various phase-separated nuclear bodies (NBs) coexist, with Pol II playing a critical role in transcription and interacting with CBs and HLBs. PCs increase during S phase, coinciding with the activation of histone genes, and form ternary associations with CBs and HLBs.
Article
Biochemistry & Molecular Biology
Ai Kaiho-Soma, Yoshino Akizuki, Katsuhide Igarashi, Akinori Endo, Takuji Shoda, Yasuko Kawase, Yosuke Demizu, Mikihiko Naito, Yasushi Saeki, Keiji Tanaka, Fumiaki Ohtake
Summary: The study reveals that the ubiquitin ligase TRIP12 and K29/K48-branched ubiquitin chains play crucial roles in targeted protein degradation, accelerating the degradation process induced by PROTACs. This cooperative mechanism is unique and enhances the efficiency of degrading neo-substrates.
Article
Oncology
Yuina Sonohara, Reine Takatsuka, Chikahide Masutani, Shigenori Iwai, Isao Kuraoka
Summary: The study demonstrates that acetaldehyde-induced DNA lesions can be repaired through the nucleotide excision repair (NER) mechanism, while also generating reversible GG crosslinks. Experimental evidence suggests that DNA polymerase eta may induce G to T transversions in acetaldehyde-treated DNA.
Article
Biotechnology & Applied Microbiology
Hidehiko Kawai, Kentaro Yazama, Yuri Yanai, Ryotaro Kamitsubo, Hiroyuki Kamiya
Summary: The study found that 5'-TDs with 100-base ss editor DNAs were as effective in gene correction as those with longer editor DNAs. Additionally, the antisense strand was more effective as the editor than the sense strand. These results suggest that 5'-TD fragments with shorter editor strands are useful for gene correction.
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Takumi Tsunoda, Miho Riku, Norika Yamada, Hikaru Tsuchiya, Takuya Tomita, Minako Suzuki, Mari Kizuki, Akihito Inoko, Hideaki Ito, Kenta Murotani, Hideki Murakami, Yasushi Saeki, Kenji Kasai
Summary: HECT-type ubiquitin E3 ligases, such as ITCH, play important roles in cellular functions by ubiquitinating various substrates. FAM189A2, a downregulated gene in breast cancer, acts as a unique activator for ITCH to regulate CXCR4 activity in endosomes, influencing chemotaxis and mammosphere formation of breast cancer cells.
Article
Chemistry, Medicinal
Hidetomo Yokoo, Norihito Shibata, Akinori Endo, Takahito Ito, Yuta Yanase, Yuki Murakami, Kiyonaga Fujii, Kengo Hamamura, Yasushi Saeki, Mikihiko Naito, Kosuke Aritake, Yosuke Demizu
Summary: PROTAC, an important modality for targeted protein degradation, requires careful selection of appropriate linker, E3 ligase ligand, and target protein ligand for successful development. In silico simulation can be a useful tool for rational development of PROTACs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Kiichi Shimabukuro, Takahiro Fukazawa, Akinori Kanai, Hidehiko Kawai, Kengo Mekata, Nobuyuki Hirohashi, Naoya Kakimoto, Keiji Tanimoto
Summary: This study evaluated the effects of low-dose-rate ionizing radiation on global gene expression in human cells. It found that low-dose-rate radiation modifies gene expression and cell cycle control, resulting in reduced sensitivity to anti-cancer chemotherapy in non-cancer cells.
Article
Biotechnology & Applied Microbiology
Hidehiko Kawai, Ryotaro Kamitsubo, Hiroyuki Kamiya
Summary: Mutations of important genes can cause various disorders, including cancer. Recent research has shown that a new version of a double-stranded structure can correct base substitution mutations in target genes in human cells. The experiments demonstrated the effective gene editing capabilities of this structure.
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
(2022)
Article
Biology
Rie Kanao, Hidehiko Kawai, Toshiyasu Taniguchi, Minoru Takata, Chikahide Masutani
Summary: PCNA modifications at K164 play a crucial role in DNA damage tolerance pathways by overcoming replication blockages and enhancing cellular resistance to alkylating compounds. Polκ and RFWD3 contribute to tolerance and their contributions are dependent on PCNA modifications, but independent of Polη.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Yoshino Akizuki, Mai Morita, Yuki Mori, Ai Kaiho-Soma, Shivani Dixit, Akinori Endo, Marie Shimogawa, Gosuke Hayashi, Mikihiko Naito, Akimitsu Okamoto, Keiji Tanaka, Yasushi Saeki, Fumiaki Ohtake
Summary: Targeted protein degradation through chemical hijacking of E3 ubiquitin ligases is a new concept in precision medicine. This study reveals the importance of K63-linked ubiquitin chains and UBE2N in degrader-induced proteasomal degradation and demonstrates the diversity of the ubiquitin code used for chemical hijacking.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Microbiology
Hirohito Ishigaki, Fumihiko Yasui, Misako Nakayama, Akinori Endo, Naoki Yamamoto, Kenzaburo Yamaji, Cong Thanh Nguyen, Yoshinori Kitagawa, Takahiro Sanada, Tomoko Honda, Tsubasa Munakata, Masahiko Higa, Sakiko Toyama, Risa Kono, Asako Takagi, Yusuke Matsumoto, Aya Koseki, Kaori Hayashi, Masanori Shiohara, Koji Ishii, Yasushi Saeki, Yasushi Itoh, Michinori Kohara
Summary: The rDIs-S vaccine, developed using the attenuated vaccinia virus Dairen-I (DIs) strain platform carrying the SARS-CoV-2 S gene, has shown broad and durable protective immunity against various strains of SARS-CoV-2 in animal and mouse models. Proteomic analysis revealed that the vaccine can prevent and restore protein expression related to the pathogenic effects and immune response of SARS-CoV-2 infection. Long-term studies also demonstrated that vaccination with rDIs-S maintains S protein-specific antibody titers for at least 6 months.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yohei Sugimoto, Yuji Masuda, Shigenori Iwai, Yumi Miyake, Rie Kanao, Chikahide Masutani
Summary: AP sites are DNA lesions that cause cytotoxicity, replication-blocks, and mutations. HMCES interacts with AP sites in single stranded DNA to form stable thiazolidine protein-DNA crosslinks and protect cells. The crosslinked HMCES is degraded by proteasome, and APE1 can incise the protease-digested HMCES adducts. These findings provide insights into the damage tolerance and repair pathways for HMCES-DNA crosslinks in human cells.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yoko Hasegawa, Thais Huarancca Reyes, Tomohiro Uemura, Anirban Baral, Akari Fujimaki, Yongming Luo, Yoshie Morita, Yasushi Saeki, Shugo Maekawa, Shigetaka Yasuda, Koki Mukuta, Yoichiro Fukao, Keiji Tanaka, Akihiko Nakano, Junpei Takagi, Rishikesh P. Bhalerao, Junji Yamaguchi, Takeo Sato
Summary: This study identified the interaction between the trans-Golgi network/early endosome localized SNARE protein SYP61 and the transmembrane ubiquitin ligase ATL31 in Arabidopsis. It also revealed the critical role of SYP61 in plant responses to nutrient stress, as well as its ubiquitination under low carbon/high nitrogen conditions. These findings provide important insights into the ubiquitin signaling and membrane trafficking machinery in plants.