Article
Immunology
Mohammed Asaad, Md Kaisar Ali, M. A. Abo-kadoum, Nzungize Lambert, Zhen Gong, Hao Wang, Moure Uae, Stech A. E. Nazou, Zhongmei Kuang, Jianping Xie
Summary: PPE10 plays a significant role in host-pathogen interaction by enhancing Mycobacterium tuberculosis's resistance to stress conditions and regulating host cell apoptosis through the expression of apoptosis-related proteins. The study provides novel insights into the mechanism of action of the PPE gene family.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Anna Aalto, Gabriela Martinez-Chacon, Christa Kietz, Nadezhda Tsyganova, Joose Kreutzer, Pasi Kallio, Meike Broemer, Annika Meinander
Summary: M1-Ub chains play a critical role in the NF-κB signaling pathway during inflammatory response induced by stress conditions in both flies and mammals. The linear ubiquitin E3 ligase LUBEL in flies catalyzes the formation of M1-Ub chains and protects flies from stress-induced death by activating the NF-κB signaling pathway.
Article
Biochemistry & Molecular Biology
Fang Hua, Wenzhuo Hao, Lingyan Wang, Shitao Li
Summary: EGFR-mediated NF-kappa B activation requires the involvement of PKP2 and LUBAC. Upon EGF stimulation, EGFR recruits PKP2 to the plasma membrane, activating the LUBAC complex and leading to NF-kappa B activation, which is crucial for tumor cell proliferation and development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biophysics
Yanjun Li, Kei Okatsu, Shuya Fukai, Yusuke Sato
Summary: TAB2-binding protein 2 (TAB2) is known to bind K63-linked polyubiquitin chains via its C-terminal Npl4 zinc-finger (NZF) domain, but recent research reveals its interaction with K6-linked polyubiquitin chains as well. The crystal structure analysis shows that TAB2-NZF can interact with both distal and proximal ubiquitin moieties of K6-Ub2, similar to its interaction with K63-Ub2, except for the flexible C-terminal region of the distal ubiquitin. This study sheds light on the dual specificity of TAB2-NZF towards K6- and K63-linked ubiquitin chains.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Cong Jiang, Xiaoming Dai, Shaohui He, Hongfei Zhou, Lan Fang, Jianping Guo, Songlei Liu, Tao Zhang, Weijuan Pan, Haihong Yu, Tianmin Fu, Dali Li, Hiroyuki Inuzuka, Ping Wang, Jianru Xiao, Wenyi Wei
Summary: The Ring domains of Mios, WDR24, and WDR59 are crucial for amino acid-induced mTORC1 activation through maintaining the integrity of GATOR2. The disruption of Mios Ring domain leads to self-ubiquitination of WDR24, preventing mTORC1 activation and resulting in severe growth defects and embryonic lethality at E10.5 in mice.
Article
Multidisciplinary Sciences
Di Wu, Haomin Li, Mingwei Liu, Jun Qin, Yi Sun
Summary: This study reveals that the absence of Rbx1, a component of Cullin-RING ligases, in regulatory T cells leads to a severe inflammatory disease. The Ube2m-Rbx1 axis is specifically required for intrinsic regulatory processes in Treg cells.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Laura Griewahn, Madeleine Mueller-Foxworth, Lukas Peintner, Manuela Wissler, Martina Weiss, Prisca Brauns-Schubert, Ramin Massoumi, Christoph Borner, Olaf Gross, Monica Yabal, Celine Charvet, Ulrich Maurer
Summary: SPATA2 bridges the interaction between CYLD and HOIP, a component of the LUBAC, thereby mediating the recruitment of CYLD to immune receptor complexes. In addition, SPATA2 competes with OTULIN for binding to HOIP, promoting autoubiquitylation of LUBAC and attenuating pro-inflammatory signaling. These findings highlight the independent functions of SPATA2 and CYLD in immune regulation.
Article
Microbiology
Bidisha Mitra, Nina Rose Beri, Rui Guo, Eric M. Burton, Laura A. Murray-Nerger, Benjamin E. Gewurz
Summary: This study found that two protein regions, TES1 and TES2, of the oncogene latent membrane protein 1 (LMP1) in the Epstein-Barr virus have different roles in the transformation and survival of B lymphocytes. TES1 signaling is critical for the survival of lymphoblastoid cell lines (LCL), while TES2 signaling has no effect on their survival. These findings contribute to understanding the functional mechanism of the LMP1 gene, and suggest that TES1 may be an important therapeutic target.
Article
Multidisciplinary Sciences
Esther Hoste, Kim Lecomte, Karl Annusver, Niels Vandamme, Jana Roels, Sophia Maschalidi, Lien Verboom, Hanna-Kaisa Vikkula, Mozes Sze, Lisette Van Hove, Kevin Verstaen, Arne Martens, Tino Hochepied, Yvan Saeys, Kodi Ravichandran, Maria Kasper, Geert van Loo
Summary: The study demonstrates that deficiency of OTULIN in keratinocytes causes skin inflammation and verrucous carcinoma through inducing keratinocyte death, highlighting the critical role of OTULIN in maintaining immune homeostasis in the skin.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Gilad Goldhirsh, Yelena Kravtsova-Ivantsiv, Gandhesiri Satish, Tamar Ziv, Ashraf Brik, Aaron Ciechanover
Summary: NF-kappa B is a crucial transcriptional regulator that relies on the UPS for activation and employs the ubiquitin ligase KPC1 for ubiquitination of p105 to generate p50, suppressing tumor growth. By linking the short amino acid sequence WILVRLW to the ligase, it can effectively bind p105 and limit cell growth.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Hirohisa Miyashita, Daisuke Oikawa, Seigo Terawaki, Daijiro Kabata, Ayumi Shintani, Fuminori Tokunaga
Summary: The study reveals that NDP52 suppresses canonical NF-kappa B signaling through its ubiquitin-binding properties and cooperatively regulates innate immune responses, apoptosis, and xenophagy with LUBAC.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Yasuhiro Fuseya, Kazuhiro Iwai
Summary: Linear ubiquitin chains play crucial roles in cell survival, proliferation, immune response, and bacterial clearance; these chains regulate physiological processes by controlling inflammatory responses and cell death; LUBAC, a complex containing two different ubiquitin ligases, interacts with deubiquitinating enzymes to regulate linear ubiquitination.
Article
Multidisciplinary Sciences
John Victor Napoleon, Satish Sagar, Sydney P. Kubica, Lidia Boghean, Smit Kour, Hannah M. King, Yogesh A. Sonawane, Ayrianne J. Crawford, Nagsen Gautam, Smitha Kizhake, Pawel A. Bialk, Eric Kmiec, Jayapal Reddy Mallareddy, Prathamesh P. Patil, Sandeep Rana, Sarbjit Singh, Janani Prahlad, Paul M. Grandgenett, Gloria E. O. Borgstahl, Gargi Ghosal, Yazen Alnouti, Michael A. Hollingsworth, Prakash Radhakrishnan, Amarnath Natarajan
Summary: Activation of IKK beta, characterized by phosphorylation of serine residues 177 and 181, has been implicated in the early onset of cancer. This study used various models to assess the role of IKK beta and its activation in cancer, and identified 39-100 as a potent inhibitor of MAP3K1. It was found that IKK beta activation is critical for tumor growth in Kras mutant pancreatic cancer, and the compound 39-100 inhibits MAP3K1-mediated IKK beta phosphorylation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Massimo Martinelli, Gabrielle Aguilar, David S. M. Lee, Andrew Kromer, Nhu Nguyen, Benjamin J. Wilkins, Tatiana Akimova, Ulf H. Beier, Louis R. Ghanem
Summary: The RNA-binding protein Pcbp2 is crucial for mouse development and is widely expressed in the immune systems. Its deletion in CD4(+) T cells affects T conventional cell proliferation by regulating co-stimulatory signaling. Pcbp2 deficiency does not impact Treg abundance or function, but is associated with peripheral CD4(+) lymphocyte population maintenance and optimal in vivo Tconv cell activation.
Article
Biochemistry & Molecular Biology
Helena C. Teague, Charlotte Lefevre, Eva Rieser, Lina Wolfram, Diego de Miguel, Daniel Patricio de Oliveira, Marisa Oliveira, Daniel S. Mansur, Nerea Irigoyen, Henning Walczak, Brian J. Ferguson
Summary: The ability of cells to mount an interferon response to virus infections depends on the intracellular nucleic acid sensing pattern recognition receptors (PRRs). The study shows that the linear ubiquitin chain assembly complex (LUBAC) regulates RIG-I signaling, indicating its role in antiviral innate immune responses.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Chemistry, Multidisciplinary
Kaiming Zhang, Naoki Horikoshi, Shanshan Li, Alexander S. Powers, Mikhail A. Hameedi, Grigore D. Pintilie, Hee-Don Chae, Yousuf A. Khan, Carl-Mikael Suomivuori, Ron O. Dror, Kathleen M. Sakamoto, Wah Chiu, Soichi Wakatsuki
Summary: In this study, a protein double shell was engineered to overcome the size limitation of determining structures of flexible proteins smaller than 30 kDa. This approach successfully determined the structure of the 11 kDa KIX domain of CBP, and molecular dynamics simulations were used to design peptides that block protein-protein interactions. The findings provide insights for the development of next-generation inhibitors.
ACS CENTRAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Irimpan I. Mathews, Naoki Horikoshi, Tsutomu Matsui, Manat Kaur, Soichi Wakatsuki, Daria Mochly-Rosen, Adriana Ann Garcia
Summary: This study identified a small molecule that activates G6PD variants by stabilizing the allosteric NADP(+) and dimer complex, suggesting potential therapeutic strategies for G6PD deficiency. The connection between allosteric NADP+ binding, oligomerization, and pathogenicity was elucidated, and stabilizing the dimer and tetramer was found to improve protein stability and activity. These findings provide a foundation for future drug discovery efforts.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Hasan DeMirci, Yashas Rao, Gabriele M. Stoffel, Bastian Vogeli, Kristina Schell, Aharon Gomez, Alexander Batyuk, Cornelius Gati, Raymond G. Sierra, Mark S. Hunter, E. Han Dao, Halil Ciftci, Brandon Hayes, Fredric Poitevin, Po-Nan Li, Manat Kaur, Kensuke Tono, David Adrian Saez, Samuel Deutsch, Yasuo Yoshikuni, Helmut Grubmueller, Tobias J. Erb, Esteban Vohringer-Martinez, Soichi Wakatsuki
Summary: This study used various experimental methods to investigate the structural organization of ECR in Kitasatospora setae, and found that its catalytic activity is carried out by a pair of dimers. The results reveal the dynamic organization and synchronized inter- and intrasubunit communications of this enzyme during catalysis.
ACS CENTRAL SCIENCE
(2022)
Review
Cell Biology
Ivan Dikic, Brenda A. Schulman
Summary: Recent studies have advanced our understanding of ubiquitylation, revealing unconventional ubiquitylation mechanisms used by pathogens to promote infection. Structural studies have shown that ubiquitin functions involve complex multivalent interactions that regulate transcription or protein degradation. Furthermore, these interactions can induce conformational changes and regulate protein degradation or transcription. These newly discovered mechanisms provide potential opportunities for innovative therapeutic interventions for diseases such as cancer and infectious diseases.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Mikhail Ali Hameedi, Erica T. Prates, Michael R. Garvin, Irimpan Mathews, B. Kirtley Amos, Omar Demerdash, Mark Bechthold, Mamta Iyer, Simin Rahighi, Daniel W. Kneller, Andrey Kovalevsky, Stephan Irle, Van-Quan Vuong, Julie C. Mitchell, Audrey Labbe, Stephanie Galanie, Soichi Wakatsuki, Daniel Jacobson
Summary: The authors report on the crystallographic and computational studies that explain how SARS-CoV-2 3CLpro cleaves NF-kappa B Essential Modulator, a host protein, in addition to its viral substrates. They discuss the association between this cleavage and the high adaptability of SARS-CoV-2 in humans. The study provides insights into the binding mechanism between 3CLpro and NEMO, as well as the role of key binding residues in the fitness of SARS-CoV-2.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Nai-Chi Chen, Chun-Hsiung Wang, Masato Yoshimura, Yi-Qi Yeh, Hong-Hsiang Guan, Phimonphan Chuankhayan, Chien-Chih Lin, Pei-Ju Lin, Yen-Chieh Huang, Soichi Wakatsuki, Meng-Chiao Ho, Chun-Jung Chen
Summary: Understanding the structural diversity of honeybee-infecting viruses is crucial for protecting pollinator health and managing disease spread in ecology and agriculture. This study used cryo-EM to determine the structures of T=4 and T=3 capsids of Lake Sinai virus (LSV) 2 and delta-N48 LSV1. The analysis revealed unique structural features and interactions of the capsid proteins, as well as the impact of pH on capsid conformations and particle sizes.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Alexandra Hertel, Ludovico Martins Alves, Henrik Dutz, Georg Tascher, Florian Bonn, Manuel Kaulich, Ivan Dikic, Stefan Eimer, Florian Steinberg, Anja Bremm
Summary: This study revealed a mechanism of controlling mTORC1 activation cascade at lysosomes through USP32-regulated LAMTOR1 ubiquitination.
Article
Chemistry, Multidisciplinary
David A. Perez A. Berrocal, Thimmalapura M. Vishwanatha, Daniel Horn-Ghetko, J. Josephine Botsch, Laura A. Hehl, Sebastian Kostrhon, Mohit Misra, Ivan Dikic, Paul P. Geurink, Hans van Dam, Brenda A. Schulman, Monique P. C. Mulder
Summary: Protein post-translational modification with ubiquitin (Ub) is a versatile signal regulating cell biology, and diseases associated with impaired Ub modification present opportunities for novel targeted treatments. The final components of the ubiquitination cascade, E3 ligases, have potential as small molecule targets. UbSRhodol, an autoimmolative Ub-based probe, enables detection of changes in E3 transthiolation activity, making it suitable for high-throughput screening and identification of small molecules modulating E3 activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Editorial Material
Biochemistry & Molecular Biology
Angus I. Lamond, Ivan Dikic, Andre Nussenzweig, Christoph W. Mueller, Janet M. Thornton, Michael B. Yaffe
Article
Cell Biology
Anshu Bhattacharya, Rukmini Mukherjee, Santosh Kumar Kuncha, Melinda Elaine Brunstein, Rajeshwari Rathore, Stephan Junek, Christian Muench, Ivan Dikic
Summary: Acute lysosomal membrane damage reduces functional lysosomes, but they have a recovery potential independent of lysosomal biogenesis and remain unaffected in cells depleted in TFEB and TFE3. A lysosomal membrane regeneration pathway was discovered that depends on ATG8, LIMP2, TBC1D15, dynamin-2, kinesin-5B, and clathrin. LIMP2 acts as a lysophagy receptor, binding ATG8, which recruits TBC1D15 to damaged lysosomal membranes. TBC1D15 interacts with ATG8 proteins and stabilizes the autophagic lysosomal reformation machinery, promoting lysosomal tubule formation and dynamin-2-dependent scission.
NATURE CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Brian C. Sanders, Suman Pokhrel, Audrey D. Labbe, Irimpan I. Mathews, Connor J. Cooper, Russell B. Davidson, Gwyndalyn Phillips, Kevin L. Weiss, Qiu Zhang, Hugh O'Neill, Manat Kaur, Jurgen G. Schmidt, Walter Reichard, Surekha Surendranathan, Jyothi Parvathareddy, Lexi Phillips, Christopher Rainville, David E. Sterner, Desigan Kumaran, Babak Andi, Gyorgy Babnigg, Nigel W. Moriarty, Paul D. Adams, Andrzej Joachimiak, Brett L. Hurst, Suresh Kumar, Tauseef R. Butt, Colleen B. Jonsson, Lori Ferrins, Soichi Wakatsuki, Stephanie Galanie, Martha S. Head, Jerry M. Parks
Summary: Designed a series of protease inhibitors targeting SARS-CoV-2, with the most effective inhibitor capable of blocking viral replication in mammalian cells and showing no significant inhibition of human proteases. These findings present an opportunity for the development of protease inhibitors.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
James S. Davies, Michael J. Currie, Rachel A. North, Mariafrancesca Scalise, Joshua D. Wright, Jack M. Copping, Daniela M. Remus, Ashutosh Gulati, Dustin R. Morado, Sam A. Jamieson, Michael C. Newton-Vesty, Gayan S. Abeysekera, Subramanian Ramaswamy, Rosmarie Friemann, Soichi Wakatsuki, Jane R. Allison, Cesare Indiveri, David Drew, Peter D. Mace, Renwick C. J. Dobson
Summary: The researchers report the structure of the TRAP transporter and propose a model for substrate transport using an 'elevator-with-an-operator' mechanism.
NATURE COMMUNICATIONS
(2023)
Review
Immunology
Joao Mello-Vieira, Tobias Bopp, Ivan Dikic
Summary: Cell-autonomous immunity is the first line of defense for cells to recognize and eliminate invasive pathogens. Ubiquitination plays a crucial role in orchestrating immune signaling networks and stimulating the appropriate immune response. This review focuses on how ubiquitin connects pathogen sensing pathways to cellular responses and discusses therapeutic options for enhancing cell-autonomous immune responses.
CURRENT OPINION IN IMMUNOLOGY
(2023)
Article
Cell Biology
Alexis Gonzalez, Ivan Dikic
Meeting Abstract
Oncology
Alicia Haydo, Johanna Ertl, Jennifer Schmidt, Marina E. Hoffmann, Stephanie Hehlgans, Alisha Crider, Rajeshwari Rathore, Christel Herold-Mende, Ivan Dikic, Mingji Dai, Alexander Adibekian, Franz Roedel, Donat Koegel, Benedikt Linder
STRAHLENTHERAPIE UND ONKOLOGIE
(2023)