Article
Biochemistry & Molecular Biology
Roslin J. Adamson, N. Connor Payne, Sergio G. Bartual, Ralph Mazitschek, Alex N. Bullock
Summary: KEAP1 promotes the ubiquitin-dependent degradation of NRF2 by assembling into a CUL3-dependent ubiquitin ligase complex. Oxidative and electrophilic stress inhibit KEAP1, allowing NRF2 to accumulate for stress response gene transactivation. The crystal structure of the BTB and 3-box domains of human KEAP1 in complex with the CUL3 N-terminal domain revealed a heterotetrameric assembly with 2:2 stoichiometry. The developed TRFRET-based assay system and binding profile data provide valuable insights into the KEAP1-CUL3 interaction.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Review
Microbiology
Robert J. Ingham, Farynna Loubich Facundo, Jianing Dong
Summary: This review examines the Ub-dependent and -independent activities of ANKR/F-box proteins in poxviruses and discusses how these proteins are used to counteract the host immune response and influence various cellular processes.
Review
Biochemistry & Molecular Biology
J. Wade Harper, Brenda A. Schulman
Summary: Cullin-RING ubiquitin ligases (CRLs) are modular platforms that regulate biological processes by ubiquitylating specific targets. Regulation is achieved through dynamic control of activation and substrate ubiquitylation, and CRLs provide a vast landscape for developing small molecules that reshape interactions and promote targeted turnover of proteins. Ultimately, the dynamics of substrate receptor interchange in CRLs drive the turnover of selected proteins to influence cellular decision-making.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Article
Cell Biology
Jiansong Liu, Yichen Zang, Cunying Ma, Dandan Wang, Zhuangfei Tian, Xia Xu, Wenjuan Li, Jihui Jia, Zhifang Liu
Summary: This study reveals that STYX acts as an oncogene in gastric cancer (GC) by inhibiting the degradation function of FBXO31, and may serve as a potential therapeutic target and prognostic biomarker in GC. STYX's interaction with FBXO31 and its regulation by c-Jun and Helicobacter pylori are key mechanisms driving GC progression.
CELL DEATH & DISEASE
(2022)
Editorial Material
Plant Sciences
Yusheng Zhao, Zhiyong Liu
Summary: Zhang et al. (2023) demonstrated through association analysis that the wheat E3 ubiquitin ligase TaAIRP2-1B positively regulates spike length by involving an upstream regulator, TaERF3, and a downstream target, TaHIPP3. This study provides a deeper understanding of spike architecture regulation and offers an alternative molecular module for designing wheat with increased yield potential.
JOURNAL OF EXPERIMENTAL BOTANY
(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
Biochemistry & Molecular Biology
Ting Zhao, Congbo Huang, Shengzhi Li, Mengqiong Jia, Ling Wang, Yujin Tang, Chaohong Zhang, Yan Li
Summary: In this study, a grape F-box E3 ubiquitin ligase VviKFB07 associated with the metabolism of stilbene and flavonoid was identified. Overexpression of VviKFB07 led to a decrease in flavonol and anthocyanin content in corolla and promoted the accumulation of resveratrol in grape callus. Further experiments confirmed the physical interaction between VviKFB07 and VviCHSs proteins and the involvement of VviKFB07 in the ubiquitination and degradation of VviCHSs protein. These findings clarify the role of ubiquitin ligase VviKFB07 in the synthesis of stilbene and flavonoid in grapes.
Review
Biochemistry & Molecular Biology
Artem Bonchuk, Konstantin Balagurov, Pavel Georgiev
Summary: The article provides a translation of the importance of BTB/POZ domains in eukaryotic organisms, as well as their role in various developmental processes and oncological diseases. Structural studies have revealed the principles of protein-protein interactions mediated by BTB domains and provided a basis for specific inhibition of these interactions. BTB domains originated early in evolution and progressively adapted to perform different functions. The article also proposes an updated structure-based classification of BTB domain families and discusses their evolutionary interconnections.
Review
Microbiology
Sian Lant, Carlos Maluquer de Motes
Summary: This review highlights the crucial role of the ubiquitin system in regulating cellular functions and combating viral infections, as well as the strategies utilized by viruses to manipulate this system. Understanding the interactions between the ubiquitin system and viruses can lead to the discovery of new antiviral treatments and insights into viral pathogenesis and host responses.
Article
Oncology
Xintong Liu, Emiko Sanada, Jiang Li, Xiaomeng Li, Hiroyuki Osada, Nobumoto Watanabe
Summary: Beta-transducin repeat-containing protein (beta-TrCP) is an F-box protein subunit of the E3 Skp1-Cullin-F box (SCF) ubiquitin-ligase complex. We developed a high-throughput screening system to identify small molecule ligands of beta-TrCP, and obtained several hit compounds that effectively inhibited beta-TrCP in cells. In silico analysis revealed the important moieties of these hit compounds and their hydrogen bonding with beta-TrCP.
Article
Cell Biology
Andrew W. Boland, Elisabet Gas-Pascual, Hanke van der Wel, Hyun W. Kim, Christopher M. West
Summary: This study examines the essential role of FbxwD and Vwa1 in the development of Dictyostelium. The interaction between these two proteins was confirmed, and changes in their expression levels during multicellular development suggested their co-functioning. Overexpression of FbxwD interfered with terminal cell differentiation, while overexpression of different domains of Vwa1 arrested development, indicating their importance in multicellular development. This research provides insights into the mechanisms of cell development and related diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Shujaat Hussain, Jianshu Dong, Xinli Ma, Jian Li, Shen Chen, Agboybor Clement, Hongmin Liu
Summary: F-box proteins are important in various cellular processes and are associated with tumorigenesis, cancer development, and progression. However, the expression and function of FBXO9 differ in different types of human cancer. Further genetic and mechanistic studies are needed to elucidate the role of FBXO9, and targeting F-box proteins or F-box protein signaling pathways could be an effective strategy for cancer therapy.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Cell Biology
Mei Ji, Zhao Zhao, Yue Li, Penglin Xu, Jia Shi, Zhe Li, Kaige Wang, Xiaotian Huang, Bin Liu
Summary: FBXO6 was identified as the ubiquitin E3 ligase for RNASET2, promoting its instability through ubiquitin-mediated proteasome degradation pathway. High expression of FBXO6 was associated with poor overall survival in ovarian cancer patients, suggesting a potential therapeutic target for ovarian cancer treatment.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Tomoki Shibuya, Manabu Nishiyama, Kazuhisa Kato, Yoshinori Kanayama
Summary: SlFKF1, a homolog of FKF1 in tomato, a day-neutral plant with fleshy fruit, may have similar functions to Arabidopsis thaliana FKF1. It is involved in the regulation of flowering and fruit ripening, and its expression is influenced by blue light. This study provides insights into the diverse physiological roles of FKF1 in plants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Christopher T. D. Price, Yousef Abu Kwaik
Summary: The ubiquitin pathway is highly conserved and important in eukaryotic cells, with many intracellular bacterial pathogens targeting this pathway. Legionella pneumophila injects various ubiquitin-modifying enzymes into host cells to modulate ubiquitin-related processes, highlighting the evolution and importance of this pathway in pathogenesis.
Article
Virology
Karla Kirkegaard, Nicholas J. van Buuren, Roberto Mateo
CURRENT OPINION IN VIROLOGY
(2016)
Article
Microbiology
Christopher J. Neufeldt, Michael A. Joyce, Nicholas Van Buuren, Aviad Levin, Karla Kirkegaard, Michael Gale, D. Lorne J. Tyrrell, Richard W. Wozniak
Article
Gastroenterology & Hepatology
Nicholas van Buuren, Lorraine Fradette, Jason Grebely, Alexandra King, Mel Krajden, Sonya A. MacParland, Alison Marshall, Sahar Saeed, Joyce Wilson, Marina B. Klein, Selena M. Sagan
CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2016)
Article
Biology
Nicholas van Buuren, Timothy Tellinghuisen, Christopher D. Richardson, Karla Kirkegaard
Article
Multidisciplinary Sciences
Julia L. Rintoul, Jiahu Wang, Don B. Gammon, Nicholas J. van Buuren, Kenneth Garson, Karen Jardine, Michele Barry, David H. Evans, John C. Bell
Article
Microbiology
Nicholas van Buuren, Kristin Burles, Jill Schriewer, Ninad Mehta, Scott Parker, R. Mark Buller, Michele Barry
Editorial Material
Gastroenterology & Hepatology
Sonya A. MacParland, Marc Bilodeau, Jason Grebely, Julie Bruneau, Curtis Cooper, Marina Klein, Selena M. Sagan, Norma Choucha, Louise Balfour, Frank Bialystok, Mel Krajden, Jennifer Raven, Eve Roberts, Rodney Russell, Michael Houghton, D. Lorne Tyrrell, Jordan J. Feld
CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Emma Abernathy, Roberto Mateo, Karim Majzoub, Nick van Buuren, Sara W. Bird, Jan E. Carette, Karla Kirkegaard
Article
Microbiology
Yaw Shin Ooi, Karim Majzoub, Ryan A. Flynn, Miguel A. Mata, Jonathan Diep, Jason Kenichi Li, Nicholas van Buuren, Neil Rumachik, Alex G. Johnson, Andreas S. Puschnik, Caleb D. Marceau, Luwanika Mlera, Jeffrey M. Grabowski, Karla Kirkegaard, Marshall E. Bloom, Peter Sarnow, Carolyn R. Bertozzi, Jan E. Carette
NATURE MICROBIOLOGY
(2019)
Article
Immunology
Noe Rico Montanari, Ricardo Ramirez, Nick Van Buuren, Thierry P. P. van den Bosch, Michail Doukas, Jose D. Debes, Becket Feierbach, Andre Boonstra
Summary: This study found a dysregulated liver transcriptome in inactive carriers of chronic hepatitis B virus (HBV) compared to healthy liver donors, despite normal liver function. Diverse levels of HBsAg have minimal impact on the liver transcriptome in inactive carriers, but gene correlation analysis revealed correlations with leukocyte activation, recruitment, and innate responses genes.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Virology
Ricardo Ramirez, Nicholas van Buuren, Lindsay Gamelin, Cameron Soulette, Lindsey May, Dong Han, Mei Yu, Regina Choy, Guofeng Cheng, Neeru Bhardwaj, Joy Chiu, Robert C. Muench, William E. Delaney, Hongmei Mo, Becket Feierbach, Li Li
Summary: This study utilized genomics approaches to describe HBV integrations and transcriptional signatures in three HCC cell lines, revealing potential associations between HBV and host chromosomal translocations. The application of novel methods sheds new light on the complexity and potential risks of HBV integrations in HCC.
JOURNAL OF VIROLOGY
(2021)
Article
Gastroenterology & Hepatology
Noe Rico Montanari, Ricardo Ramirez, Abhishek Aggarwal, Nick van Buuren, Michael Doukas, Christina Moon, Scott Turner, Lauri Diehl, Li Li, Jose D. Debes, Becket Feierbach, Andre Boonstra
Summary: In this study, the immunological composition and transcriptional profiles of liver samples from patients with chronic HBV were compared to healthy controls. The results showed distinct inflammatory profiles and gene expression differences in chronic HBV phases compared to healthy liver, indicating the complex interplay between the immune system and the virus in the liver.
JOURNAL OF HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Nicholas van Buuren, Ricardo Ramirez, Cameron Soulette, Vithika Suri, Dong Han, Lindsey May, Scott Turner, P. C. Parvangada, Ross Martin, Henry L. Y. Chan, Patrick Marcellin, Maria Buti, Nam Bui, Neeru Bhardwaj, Anuj Gaggar, Li Li, Hongmei Mo, Becket Feierbach
Summary: The study utilized targeted long-read sequencing to analyze HBV integration events in liver biopsies, revealing chromosomal translocation associated with HBV integration. Long-read RNA sequencing allowed for accurate quantification of HBV transcriptome, with patients showing differences in transcription origin based on HBeAg status. The findings suggest a novel mechanism with mutagenic potential that may contribute to HCC progression.
Article
Gastroenterology & Hepatology
Nicholas van Buuren, Ricardo Ramirez, Scott Turner, Diana Chen, Vithika Suri, Abhishek Aggarwal, Christina Moon, Sam Kim, Dmytro Kornyeyev, Nam Bui, Neeru Bhardwaj, Henry Ly Chan, Patrick Marcellin, Maria Buti, Jeffrey Wallin, Anuj Gaggar, Simon P. Fletcher, Lauri Diehl, Li Li, Hongmei Mo, Becket Feierbach
Summary: By analyzing liver biopsies from patients with chronic HBV infection using RNA-Seq and a custom multiplex immunofluorescence panel, two distinct liver immune microenvironments were identified as immune high and immune low. Patients with immune high status exhibited elevated immune pathways and increased presence of immune cells.
