Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect
ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Gliotoxin Suppresses NF-κB Activation by Selectively Inhibiting Linear Ubiquitin Chain Assembly Complex (LUBAC)

View Author Information
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Open Innovation Center for Drug Discovery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
§ Department of Molecular Cell Biology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan
Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High-Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki 305-8501, Japan
Medical Innovation Center Laboratory for Malignancy Control Research/DSK, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto-shi, Kyoto 606-8501, Japan
# Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305, United States
SLAC National Accelerator Laboratory, Menlo Park, California 94025, United States
Department of Biophysics and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto-shi, Kyoto 606-8501, Japan
Cite this: ACS Chem. Biol. 2015, 10, 3, 675–681
Publication Date (Web):December 10, 2014
https://doi.org/10.1021/cb500653y
Copyright © 2014 American Chemical Society

    Article Views

    2840

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options
    Supporting Info (1)»

    Abstract

    Abstract Image

    A linear ubiquitin chain, which consists of ubiquitin molecules linked via their N- and C-termini, is formed by a linear ubiquitin chain assembly complex (LUBAC) composed of HOIP, HOIL-1L, and SHARPIN, and conjugation of a linear ubiquitin chain on the NF-κB essential modulator (NEMO) is deeply involved in NF-κB activation induced by various signals. Since abnormal activation of NF-κB is associated with inflammatory disease and malignancy, we searched for an inhibitor of LUBAC by high-throughput screening (HTS) with a Tb3+-fluorescein FRET system. As a result, we found that the fungal metabolite gliotoxin inhibits LUBAC selectively by binding to the RING-IBR-RING domain of HOIP, the catalytic center of LUBAC. Gliotoxin has been well-known as an inhibitor of NF-κB activation, though its action mechanism has remained elusive. Here, we show that gliotoxin inhibits signal-induced NF-κB activation by selectively inhibiting LUBAC-mediated linear ubiquitin chain formation.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    Figures S1–S10, Tables S1 and S2, methods, and references. This material is available free of charge via the Internet at http://pubs.acs.org

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 74 publications.

    1. Henrik Johansson, Yi-Chun Isabella Tsai, Ken Fantom, Chun-Wa Chung, Sandra Kümper, Luigi Martino, Daniel A. Thomas, H. Christian Eberl, Marcel Muelbaier, David House, Katrin Rittinger. Fragment-Based Covalent Ligand Screening Enables Rapid Discovery of Inhibitors for the RBR E3 Ubiquitin Ligase HOIP. Journal of the American Chemical Society 2019, 141 (6) , 2703-2712. https://doi.org/10.1021/jacs.8b13193
    2. Florent Péron, Stéphanie Riché, Brigitte Lesur, Marcel Hibert, Philippe Breton, Jean-Marie Fourquez, Nicolas Girard, Dominique Bonnet. Versatile Synthetic Approach for Selective Diversification of Bicyclic Aza-Diketopiperazines. ACS Omega 2018, 3 (11) , 15182-15192. https://doi.org/10.1021/acsomega.8b01752
    3. Zakey Yusuf Buuh, Zhigang Lyu, Rongsheng E. Wang. Interrogating the Roles of Post-Translational Modifications of Non-Histone Proteins. Journal of Medicinal Chemistry 2018, 61 (8) , 3239-3252. https://doi.org/10.1021/acs.jmedchem.6b01817
    4. Michael Chan, Alast Ahmadi, Shiyin Yao, Fumi Sato-Kaneko, Karen Messer, Minya Pu, Brandon Nguyen, Tomoko Hayashi, Maripat Corr, Dennis A. Carson, Howard B. Cottam, and Nikunj M. Shukla . Identification of Biologically Active Pyrimido[5,4-b]indoles That Prolong NF-κB Activation without Intrinsic Activity. ACS Combinatorial Science 2017, 19 (8) , 533-543. https://doi.org/10.1021/acscombsci.7b00080
    5. Zhengkai Wei, Qinqin Jin, Wei Liu, Tingting Liu, Kaifeng He, Zha Jin, Meiyi Chen, Yuqian Jiang, Yuxiao Qian, Hongrong Hong, Dezhi Zhang, Quan Liu, Zhengtao Yang, Qianyong Li. Gliotoxin elicits immunotoxicity in the early innate immune system of ducks. Poultry Science 2024, 10 , 103717. https://doi.org/10.1016/j.psj.2024.103717
    6. Ze Rong, Kaifeng Zheng, Jun Chen, Xiaofeng Jin. The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer. Journal of Cancer Research and Clinical Oncology 2024, 150 (3) https://doi.org/10.1007/s00432-024-05659-9
    7. Bhaskar Basu, Satadeepa Kal, Subhajit Karmakar, Malini Basu, Mrinal K. Ghosh. E3 ubiquitin ligases in lung cancer: Emerging insights and therapeutic opportunities. Life Sciences 2024, 336 , 122333. https://doi.org/10.1016/j.lfs.2023.122333
    8. Nadine Weinelt, Kaja Nicole Wächtershäuser, Gulustan Celik, Birte Jeiler, Isabelle Gollin, Laura Zein, Sonja Smith, Geoffroy Andrieux, Tonmoy Das, Jens Roedig, Leonard Feist, Björn Rotter, Melanie Boerries, Francesco Pampaloni, Sjoerd J. L. van Wijk. LUBAC-mediated M1 Ub regulates necroptosis by segregating the cellular distribution of active MLKL. Cell Death & Disease 2024, 15 (1) https://doi.org/10.1038/s41419-024-06447-6
    9. Jack Li, Sijin Liu, Shitao Li. Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery. Cell Communication and Signaling 2023, 21 (1) https://doi.org/10.1186/s12964-023-01239-5
    10. Lin Wang, Qinghua Jiang, Siyu Chen, Siyi Wang, Jingyi Lu, Xun Gao, Dongfang Zhang, Xin Jin. Natural epidithiodiketopiperazine alkaloids as potential anticancer agents: Recent mechanisms of action, structural modification, and synthetic strategies. Bioorganic Chemistry 2023, 137 , 106642. https://doi.org/10.1016/j.bioorg.2023.106642
    11. Keito Hiragi, Akira Nishide, Kenji Takagi, Kazuhiro Iwai, Minsoo Kim, Tsunehiro Mizushima. Structural insight into the recognition of the linear ubiquitin assembly complex by Shigella E3 ligase IpaH1.4/2.5. The Journal of Biochemistry 2023, 173 (4) , 317-326. https://doi.org/10.1093/jb/mvac109
    12. Chibuzo Sampson, Qiuping Wang, Wuxiyar Otkur, Haifeng Zhao, Yun Lu, Xiaolong Liu, Hai‐long Piao. The roles of E3 ubiquitin ligases in cancer progression and targeted therapy. Clinical and Translational Medicine 2023, 13 (3) https://doi.org/10.1002/ctm2.1204
    13. Koji Jimbo, Ayuna Hattori, Shuhei Koide, Takahiro Ito, Katsuhiro Sasaki, Kazuhiro Iwai, Yasuhito Nannya, Atsushi Iwama, Arinobu Tojo, Takaaki Konuma. Genetic deletion and pharmacologic inhibition of E3 ubiquitin ligase HOIP impairs the propagation of myeloid leukemia. Leukemia 2023, 37 (1) , 122-133. https://doi.org/10.1038/s41375-022-01750-7
    14. Xijun Chen, Qing Ye, Wenxiu Zhao, Xiaoqin Chi, Chengrong Xie, Xiaomin Wang. RBCK1 promotes hepatocellular carcinoma metastasis and growth by stabilizing RNF31. Cell Death Discovery 2022, 8 (1) https://doi.org/10.1038/s41420-022-01126-x
    15. Qi Liu, Gabriel LaPlante, Wei Zhang. Targeting the Ubiquitination Cascade for Drug Discovery. 2022, 179-225. https://doi.org/10.1002/9781119774198.ch5
    16. Yanmin Guo, Jianfeng He, Hailong Zhang, Ran Chen, Lian Li, Xiaojia Liu, Caihu Huang, Zhe Qiang, Zihan Zhou, Yanli Wang, Jian Huang, Xian Zhao, Junke Zheng, Guo-Qiang Chen, Jianxiu Yu. Linear ubiquitination of PTEN impairs its function to promote prostate cancer progression. Oncogene 2022, 41 (44) , 4877-4892. https://doi.org/10.1038/s41388-022-02485-6
    17. Shuo Ning, Lingling Luo, Beiming Yu, Dina Mai, Feng Wang. Structures, functions, and inhibitors of LUBAC and its related diseases. Journal of Leukocyte Biology 2022, 112 (4) , 799-811. https://doi.org/10.1002/JLB.3MR0222-508R
    18. Mingqi Li, Ling Li, Sarah Asemota, David Kakhniashvili, Ramesh Narayanan, Xusheng Wang, Francesca-Fang Liao. Reciprocal interplay between OTULIN–LUBAC determines genotoxic and inflammatory NF-κB signal responses. Proceedings of the National Academy of Sciences 2022, 119 (33) https://doi.org/10.1073/pnas.2123097119
    19. Dhanya Krishnan, Ramsekhar N. Menon, Srinivas Gopala. SHARPIN: Role in Finding NEMO and in Amyloid-Beta Clearance and Degradation (ABCD) Pathway in Alzheimer’s Disease?. Cellular and Molecular Neurobiology 2022, 42 (5) , 1267-1281. https://doi.org/10.1007/s10571-020-01023-w
    20. Zhengkui Zhang, Xiangjun Kong, Maarten A. Ligtenberg, Susan E. van Hal-van Veen, Nils L. Visser, Beaunelle de Bruijn, Kelly Stecker, Pim W. van der Helm, Thomas Kuilman, Esmée P. Hoefsmit, David W. Vredevoogd, Georgi Apriamashvili, Beau Baars, Emile E. Voest, Sjoerd Klarenbeek, Maarten Altelaar, Daniel S. Peeper. RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells. Cell Reports Medicine 2022, 3 (6) , 100655. https://doi.org/10.1016/j.xcrm.2022.100655
    21. Fuminori Tokunaga, Fumiyo Ikeda. Linear ubiquitination in immune and neurodegenerative diseases, and beyond. Biochemical Society Transactions 2022, 50 (2) , 799-811. https://doi.org/10.1042/BST20211078
    22. Yanan Li, Shujing Li, Huijian Wu. Ubiquitination-Proteasome System (UPS) and Autophagy Two Main Protein Degradation Machineries in Response to Cell Stress. Cells 2022, 11 (5) , 851. https://doi.org/10.3390/cells11050851
    23. Andrew J. Freeman, Conor J. Kearney, John Silke, Jane Oliaro. Unleashing TNF cytotoxicity to enhance cancer immunotherapy. Trends in Immunology 2021, 42 (12) , 1128-1142. https://doi.org/10.1016/j.it.2021.10.003
    24. Hailong Zhang, Xian Zhao, Yanmin Guo, Ran Chen, Jianfeng He, Lian Li, Zhe Qiang, Qianqian Yang, Xiaojia Liu, Caihu Huang, Runhui Lu, Jiayu Fang, Yingting Cao, Jiayi Huang, Yanli Wang, Jian Huang, Guo-Qiang Chen, Jinke Cheng, Jianxiu Yu. Hypoxia regulates overall mRNA homeostasis by inducing Met1-linked linear ubiquitination of AGO2 in cancer cells. Nature Communications 2021, 12 (1) https://doi.org/10.1038/s41467-021-25739-5
    25. Peng Ye, Xiaoxia Chi, Jong-Ho Cha, Shahang Luo, Guanghui Yang, Xiuwen Yan, Wen-Hao Yang. Potential of E3 Ubiquitin Ligases in Cancer Immunity: Opportunities and Challenges. Cells 2021, 10 (12) , 3309. https://doi.org/10.3390/cells10123309
    26. Magdalena Staszczak. Fungal Secondary Metabolites as Inhibitors of the Ubiquitin–Proteasome System. International Journal of Molecular Sciences 2021, 22 (24) , 13309. https://doi.org/10.3390/ijms222413309
    27. Andrew J Freeman, Stephin J Vervoort, Jessica Michie, Kelly M Ramsbottom, John Silke, Conor J Kearney, Jane Oliaro. HOIP limits anti‐tumor immunity by protecting against combined TNF and IFN‐gamma‐induced apoptosis. EMBO reports 2021, 22 (11) https://doi.org/10.15252/embr.202153391
    28. Andrew Aboujaoude, Berge Minassian, Sharmistha Mitra. LUBAC: a new player in polyglucosan body disease. Biochemical Society Transactions 2021, 49 (5) , 2443-2454. https://doi.org/10.1042/BST20210838
    29. Zheng-Qing Li, Xiuping Chen, Ying Wang. Small molecules targeting ubiquitination to control inflammatory diseases. Drug Discovery Today 2021, 26 (10) , 2414-2422. https://doi.org/10.1016/j.drudis.2021.04.029
    30. Yasuhiro Fuseya, Kazuhiro Iwai. Biochemistry, Pathophysiology, and Regulation of Linear Ubiquitination: Intricate Regulation by Coordinated Functions of the Associated Ligase and Deubiquitinase. Cells 2021, 10 (10) , 2706. https://doi.org/10.3390/cells10102706
    31. Gabriel LaPlante, Wei Zhang. Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors. Cancers 2021, 13 (12) , 3079. https://doi.org/10.3390/cancers13123079
    32. Daniel F. Q. Smith, Arturo Casadevall. Fungal immunity and pathogenesis in mammals versus the invertebrate model organism Galleria mellonella. Pathogens and Disease 2021, 79 (3) https://doi.org/10.1093/femspd/ftab013
    33. Kazuhiro IWAI. LUBAC-mediated linear ubiquitination: a crucial regulator of immune signaling. Proceedings of the Japan Academy, Series B 2021, 97 (3) , 120-133. https://doi.org/10.2183/pjab.97.007
    34. Berthe Katrine Fiil, Mads Gyrd-Hansen. The Met1-linked ubiquitin machinery in inflammation and infection. Cell Death & Differentiation 2021, 28 (2) , 557-569. https://doi.org/10.1038/s41418-020-00702-x
    35. Kazuhiro Iwai. Discovery of linear ubiquitination, a crucial regulator for immune signaling and cell death. The FEBS Journal 2021, 288 (4) , 1060-1069. https://doi.org/10.1111/febs.15471
    36. Xu Cao, Lei Cao, Wencan Zhang, Rongzhu Lu, Jin-Song Bian, Xiaowei Nie. Therapeutic potential of sulfur-containing natural products in inflammatory diseases. Pharmacology & Therapeutics 2020, 216 , 107687. https://doi.org/10.1016/j.pharmthera.2020.107687
    37. Wei Wang, Mingqi Li, Suriyan Ponnusamy, Yayun Chi, Jingyan Xue, Beshoy Fahmy, Meiyun Fan, Gustavo A. Miranda-Carboni, Ramesh Narayanan, Jiong Wu, Zhao-Hui Wu. ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/β-catenin activation to enhance drug resistance in breast cancers. Nature Communications 2020, 11 (1) https://doi.org/10.1038/s41467-020-17770-9
    38. Daisuke Oikawa, Yusuke Sato, Fumiaki Ohtake, Keidai Komakura, Kazuki Hanada, Koji Sugawara, Seigo Terawaki, Yukari Mizukami, Hoang T. Phuong, Kiyosei Iio, Shingo Obika, Masaya Fukushi, Takashi Irie, Daisuke Tsuruta, Shinji Sakamoto, Keiji Tanaka, Yasushi Saeki, Shuya Fukai, Fuminori Tokunaga. Molecular bases for HOIPINs-mediated inhibition of LUBAC and innate immune responses. Communications Biology 2020, 3 (1) https://doi.org/10.1038/s42003-020-0882-8
    39. Zhihui Song, Wei Wei, Wenming Xiao, Essel D. Al-Saleem, Reza Nejati, Liqi Chen, Jiejing Yin, Joseph Fabrizio, Michael N. Petrus, Thomas A. Waldmann, Yibin Yang. Essential role of the linear ubiquitin chain assembly complex and TAK1 kinase in A20 mutant Hodgkin lymphoma. Proceedings of the National Academy of Sciences 2020, 117 (46) , 28980-28991. https://doi.org/10.1073/pnas.2014470117
    40. Timurs Maculins, Javier Garcia-Pardo, Anamarija Skenderovic, Jakob Gebel, Mateusz Putyrski, Andrew Vorobyov, Philipp Busse, Gabor Varga, Maria Kuzikov, Andrea Zaliani, Simin Rahighi, Veronique Schaeffer, Michael J. Parnham, Sachdev S. Sidhu, Andreas Ernst, Volker Dötsch, Masato Akutsu, Ivan Dikic. Discovery of Protein-Protein Interaction Inhibitors by Integrating Protein Engineering and Chemical Screening Platforms. Cell Chemical Biology 2020, 27 (11) , 1441-1451.e7. https://doi.org/10.1016/j.chembiol.2020.07.010
    41. Patricia L. Brazee, Jacob I. Sznajder. Targeting the Linear Ubiquitin Assembly Complex to Modulate the Host Response and Improve Influenza A Virus Induced Lung Injury. Archivos de Bronconeumología (English Edition) 2020, 56 (9) , 586-591. https://doi.org/10.1016/j.arbr.2020.04.008
    42. Patricia L. Brazee, Jacob I. Sznajder. Targeting the Linear Ubiquitin Assembly Complex to Modulate the Host Response and Improve Influenza A Virus Induced Lung Injury. Archivos de Bronconeumología 2020, 56 (9) , 586-591. https://doi.org/10.1016/j.arbres.2020.04.019
    43. Mateusz Stoszko, Abdullah M. S. Al-Hatmi, Anton Skriba, Michael Roling, Enrico Ne, Raquel Crespo, Yvonne M. Mueller, Mohammad Javad Najafzadeh, Joyce Kang, Renata Ptackova, Elizabeth LeMasters, Pritha Biswas, Alessia Bertoldi, Tsung Wai Kan, Elisa de Crignis, Miroslav Sulc, Joyce H.G. Lebbink, Casper Rokx, Annelies Verbon, Wilfred van Ijcken, Peter D. Katsikis, Robert-Jan Palstra, Vladimir Havlicek, Sybren de Hoog, Tokameh Mahmoudi. Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb, and reverses HIV-1 latency. Science Advances 2020, 6 (33) https://doi.org/10.1126/sciadv.aba6617
    44. TW Jordan. The cellular and molecular toxicity of sporidesmin. New Zealand Veterinary Journal 2020, 68 (4) , 203-213. https://doi.org/10.1080/00480169.2020.1729268
    45. Yasuhiro Fuseya, Hiroaki Fujita, Minsoo Kim, Fumiaki Ohtake, Akira Nishide, Katsuhiro Sasaki, Yasushi Saeki, Keiji Tanaka, Ryosuke Takahashi, Kazuhiro Iwai. The HOIL-1L ligase modulates immune signalling and cell death via monoubiquitination of LUBAC. Nature Cell Biology 2020, 22 (6) , 663-673. https://doi.org/10.1038/s41556-020-0517-9
    46. Daisuke Oikawa, Yusuke Sato, Hidefumi Ito, Fuminori Tokunaga. Linear Ubiquitin Code: Its Writer, Erasers, Decoders, Inhibitors, and Implications in Disorders. International Journal of Molecular Sciences 2020, 21 (9) , 3381. https://doi.org/10.3390/ijms21093381
    47. Patricia L. Brazee, Luisa Morales-Nebreda, Natalia D. Magnani, Joe G.N. Garcia, Alexander V. Misharin, Karen M. Ridge, G.R. Scott Budinger, Kazuhiro Iwai, Laura A. Dada, Jacob I. Sznajder. Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection. Journal of Clinical Investigation 2020, 130 (3) , 1301-1314. https://doi.org/10.1172/JCI128368
    48. Yi-Chun Isabella Tsai, Henrik Johansson, David Dixon, Stephen Martin, Chun-wa Chung, Jane Clarkson, David House, Katrin Rittinger. Single-Domain Antibodies as Crystallization Chaperones to Enable Structure-Based Inhibitor Development for RBR E3 Ubiquitin Ligases. Cell Chemical Biology 2020, 27 (1) , 83-93.e9. https://doi.org/10.1016/j.chembiol.2019.11.007
    49. Min Wu, Yan Chang, Huaibin Hu, Rui Mu, Yucheng Zhang, Xuanhe Qin, Xiaotao Duan, Weihua Li, Haiqing Tu, Weina Zhang, Guang Wang, Qiuying Han, Ailing Li, Tao Zhou, Kazuhiro Iwai, Xuemin Zhang, Huiyan Li. LUBAC controls chromosome alignment by targeting CENP-E to attached kinetochores. Nature Communications 2019, 10 (1) https://doi.org/10.1038/s41467-018-08043-7
    50. Katsuhiro Sasaki, Ai Himeno, Tomoko Nakagawa, Yoshiteru Sasaki, Hiroshi Kiyonari, Kazuhiro Iwai. Modulation of autoimmune pathogenesis by T cell-triggered inflammatory cell death. Nature Communications 2019, 10 (1) https://doi.org/10.1038/s41467-019-11858-7
    51. Jinho Seo, Min Wook Kim, Kwang-Hee Bae, Sang Chul Lee, Jaewhan Song, Eun-Woo Lee. The roles of ubiquitination in extrinsic cell death pathways and its implications for therapeutics. Biochemical Pharmacology 2019, 162 , 21-40. https://doi.org/10.1016/j.bcp.2018.11.012
    52. E. Josue Ruiz, Markus E. Diefenbacher, Jessica K. Nelson, Rocio Sancho, Fabio Pucci, Atanu Chakraborty, Paula Moreno, Alessandro Annibaldi, Gianmaria Liccardi, Vesela Encheva, Richard Mitter, Mathias Rosenfeldt, Ambrosius P. Snijders, Pascal Meier, Marco A. Calzado, Axel Behrens. LUBAC determines chemotherapy resistance in squamous cell lung cancer. Journal of Experimental Medicine 2019, 216 (2) , 450-465. https://doi.org/10.1084/jem.20180742
    53. Ken Katsuya, Daisuke Oikawa, Kiyosei Iio, Shingo Obika, Yuji Hori, Toshiki Urashima, Kumiko Ayukawa, Fuminori Tokunaga. Small-molecule inhibitors of linear ubiquitin chain assembly complex (LUBAC), HOIPINs, suppress NF-κB signaling. Biochemical and Biophysical Research Communications 2019, 509 (3) , 700-706. https://doi.org/10.1016/j.bbrc.2018.12.164
    54. Fumiaki Ohtake, Hikaru Tsuchiya, Keiji Tanaka, Yasushi Saeki. Methods to measure ubiquitin chain length and linkage. 2019, 105-133. https://doi.org/10.1016/bs.mie.2018.12.019
    55. Zhen Gong, Zhongmei Kuang, Hui Li, Chunyan Li, Md Kaisar Ali, Fujing Huang, Ping Li, Qiming Li, Xue Huang, Sai Ren, Jiang Li, Jianping Xie. Regulation of host cell pyroptosis and cytokines production by Mycobacterium tuberculosis effector PPE60 requires LUBAC mediated NF-κB signaling. Cellular Immunology 2019, 335 , 41-50. https://doi.org/10.1016/j.cellimm.2018.10.009
    56. Hikaru Tsuchiya, Daocharad Burana, Fumiaki Ohtake, Naoko Arai, Ai Kaiho, Masayuki Komada, Keiji Tanaka, Yasushi Saeki. Ub-ProT reveals global length and composition of protein ubiquitylation in cells. Nature Communications 2018, 9 (1) https://doi.org/10.1038/s41467-018-02869-x
    57. Swarupa Panda, Nelson O. Gekara. The deubiquitinase MYSM1 dampens NOD2-mediated inflammation and tissue damage by inactivating the RIP2 complex. Nature Communications 2018, 9 (1) https://doi.org/10.1038/s41467-018-07016-0
    58. Ken Katsuya, Yuji Hori, Daisuke Oikawa, Tomohisa Yamamoto, Kayo Umetani, Toshiki Urashima, Tomomi Kinoshita, Kumiko Ayukawa, Fuminori Tokunaga, Masahiro Tamaru. High-Throughput Screening for Linear Ubiquitin Chain Assembly Complex (LUBAC) Selective Inhibitors Using Homogenous Time-Resolved Fluorescence (HTRF)-Based Assay System. SLAS Discovery 2018, 23 (10) , 1018-1029. https://doi.org/10.1177/2472555218793066
    59. Jing Li, Yaru Zhang, Bruno Da Silva Sil Dos Santos, Feng Wang, Yuyong Ma, Christian Perez, Yanling Yang, Junmin Peng, Seth M. Cohen, Tsui-Fen Chou, Stephen T. Hilton, Raymond J. Deshaies. Epidithiodiketopiperazines Inhibit Protein Degradation by Targeting Proteasome Deubiquitinase Rpn11. Cell Chemical Biology 2018, 25 (11) , 1350-1358.e9. https://doi.org/10.1016/j.chembiol.2018.07.012
    60. Virginia De Cesare, Clare Johnson, Victoria Barlow, James Hastie, Axel Knebel, Matthias Trost. The MALDI-TOF E2/E3 Ligase Assay as Universal Tool for Drug Discovery in the Ubiquitin Pathway. Cell Chemical Biology 2018, 25 (9) , 1117-1127.e4. https://doi.org/10.1016/j.chembiol.2018.06.004
    61. Norah A. Alturki, Scott McComb, Ardeshir Ariana, Dikchha Rijal, Robert G. Korneluk, Shao-Cong Sun, Emad Alnemri, Subash Sad. Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis. Cell Death & Disease 2018, 9 (6) https://doi.org/10.1038/s41419-018-0672-0
    62. Francisco Aguilar-Alonso, Amanda L. Whiting, Ye Joon Kim, Federico Bernal. Biophysical and biological evaluation of optimized stapled peptide inhibitors of the linear ubiquitin chain assembly complex (LUBAC). Bioorganic & Medicinal Chemistry 2018, 26 (6) , 1179-1188. https://doi.org/10.1016/j.bmc.2017.11.047
    63. Hikaru Tsuchiya, Fumiaki Ohtake, Naoko Arai, Ai Kaiho, Sayaka Yasuda, Keiji Tanaka, Yasushi Saeki. In Vivo Ubiquitin Linkage-type Analysis Reveals that the Cdc48-Rad23/Dsk2 Axis Contributes to K48-Linked Chain Specificity of the Proteasome. Molecular Cell 2017, 66 (4) , 488-502.e7. https://doi.org/10.1016/j.molcel.2017.04.024
    64. Cibele Konstantinovas, Tiago A. de Oliveira Mendes, Marcos A. Vannier-Santos, Jane Lima-Santos. Modulation of Human Immune Response by Fungal Biocontrol Agents. Frontiers in Microbiology 2017, 8 https://doi.org/10.3389/fmicb.2017.00039
    65. Yusuke Kimura, Toru Komatsu, Kouichi Yanagi, Kenjiro Hanaoka, Tasuku Ueno, Takuya Terai, Hirotatsu Kojima, Takayoshi Okabe, Tetsuo Nagano, Yasuteru Urano. Development of Chemical Tools to Monitor and Control Isoaspartyl Peptide Methyltransferase Activity. Angewandte Chemie 2017, 129 (1) , 159-163. https://doi.org/10.1002/ange.201608677
    66. Yusuke Kimura, Toru Komatsu, Kouichi Yanagi, Kenjiro Hanaoka, Tasuku Ueno, Takuya Terai, Hirotatsu Kojima, Takayoshi Okabe, Tetsuo Nagano, Yasuteru Urano. Development of Chemical Tools to Monitor and Control Isoaspartyl Peptide Methyltransferase Activity. Angewandte Chemie International Edition 2017, 56 (1) , 153-157. https://doi.org/10.1002/anie.201608677
    67. Ali A Abdul-Sater, Maria I Edilova, Derek L Clouthier, Achire Mbanwi, Elisabeth Kremmer, Tania H Watts. The signaling adaptor TRAF1 negatively regulates Toll-like receptor signaling and this underlies its role in rheumatic disease. Nature Immunology 2017, 18 (1) , 26-35. https://doi.org/10.1038/ni.3618
    68. Toru Komatsu. Potential of Enzymomics Methodologies to Characterize Disease-Related Protein Functions. CHEMICAL & PHARMACEUTICAL BULLETIN 2017, 65 (7) , 605-610. https://doi.org/10.1248/cpb.c17-00144
    69. Evgenij Fiskin, Tihana Bionda, Ivan Dikic, Christian Behrends. Global Analysis of Host and Bacterial Ubiquitinome in Response to Salmonella Typhimurium Infection. Molecular Cell 2016, 62 (6) , 967-981. https://doi.org/10.1016/j.molcel.2016.04.015
    70. Patricia Brazee, Laura A. Dada, Jacob I. Sznajder. Role of Linear Ubiquitination in Health and Disease. American Journal of Respiratory Cell and Molecular Biology 2016, 54 (6) , 761-768. https://doi.org/10.1165/rcmb.2016-0014TR
    71. Takuya Terai, Hiroki Ito, Kenjiro Hanaoka, Toru Komatsu, Tasuku Ueno, Tetsuo Nagano, Yasuteru Urano. Detection of NAD(P)H-dependent enzyme activity by time-domain ratiometry of terbium luminescence. Bioorganic & Medicinal Chemistry Letters 2016, 26 (9) , 2314-2317. https://doi.org/10.1016/j.bmcl.2016.03.038
    72. Hiroki SAKAMOTO, Kazuhiro IWAI, Tetsuo NAGANO. . Kagaku To Seibutsu 2016, 54 (2) , 83-84. https://doi.org/10.1271/kagakutoseibutsu.54.83
    73. Junxiong Chen, Chenliang Wang, Wenjian Lan, Chunying Huang, Mengmeng Lin, Zhongyang Wang, Wanling Liang, Aikichi Iwamoto, Xiangling Yang, Huanliang Liu. Gliotoxin Inhibits Proliferation and Induces Apoptosis in Colorectal Cancer Cells. Marine Drugs 2015, 13 (10) , 6259-6273. https://doi.org/10.3390/md13106259
    74. Katsuhiro Sasaki, Kazuhiro Iwai. Roles of linear ubiquitinylation, a crucial regulator of NF ‐κB and cell death, in the immune system. Immunological Reviews 2015, 266 (1) , 175-189. https://doi.org/10.1111/imr.12308