Review
Biochemistry & Molecular Biology
Jessica Proulx, Kathleen Borgmann, In-Woo Park
Summary: Viruses encode viral DUBs to disrupt cellular Ub-dependent processes, evade host immune response, and enhance virus replication and proliferation within infected cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Chibuzo Sampson, Qiuping Wang, Wuxiyar Otkur, Haifeng Zhao, Yun Lu, Xiaolong Liu, Hai-long Piao
Summary: Ubiquitination, an important post-translational modification, is crucial for maintaining cellular protein homeostasis. E3 ubiquitin ligases are the most influential enzymes in the ubiquitination process and play a significant role in cancer hallmarks. The specificity of E3 ligases and their involvement in cancer hallmarks have led to the development of compounds that target them for cancer therapy. This review highlights the role of E3 ligases in cancer hallmarks and summarizes the application and significance of targeting E3 ligases as potential cancer therapy.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Review
Immunology
Niraj Parihar, Lokesh Kumar Bhatt
Summary: The ubiquitin-proteasome pathway plays a crucial role in the development of autoimmune diseases, with DUBs regulating protein ubiquitination to influence immune responses.
INFLAMMOPHARMACOLOGY
(2021)
Review
Immunology
Mingjiu Zhao, Mengdi Zhang, Zhou Yang, Zhiguang Zhou, Jiaqi Huang, Bin Zhao
Summary: Since its emergence in 2019, COVID-19 has spread rapidly worldwide, causing a pervasive pandemic that has had profound effects on healthcare systems and the socio-economic environment. Numerous studies have focused on the pathogenic virus, SARS-CoV-2, in an effort to find ways to combat COVID-19. The ubiquitin-proteasome system (UPS) is recognized as a crucial mechanism for regulating human biological activities through the maintenance of protein homeostasis. This review aims to clarify the mechanisms by which the virus utilizes host E3 ubiquitin ligases and DUBs, along with its own viral proteins with similar enzyme activities, to facilitate invasion, replication, evasion, and inflammation. Understanding the role of E3 ubiquitin ligases and DUBs in COVID-19 can provide valuable insights for the development of antiviral therapies.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Genetics & Heredity
Fengguang Zhai, Jingyun Li, Meng Ye, Xiaofeng Jin
Summary: CUL3 is a scaffold protein that forms ubiquitin ligases with the substrate recognition adaptor and RING-finger protein 1. Through non-degradative ubiquitination, CUL3-E3 ligases play crucial roles in cell cycle regulation, protein transportation, and tumorigenesis.
Article
Multidisciplinary Sciences
Virginia De Cesare, Daniel Carbajo Lopez, Peter D. Mabbitt, Adam J. Fletcher, Mathieu Soetens, Odetta Antico, Nicola T. Wood, Satpal Virdee
Summary: The study focuses on exploring the esterase and isopeptidase activity of DUBs, revealing that most DUBs exhibit dual selectivity, with the ovarian tumor domain DUB class demonstrating specific isopeptidase activity and the Machado-Joseph disease (MJD) class showing highly specific ubiquitin esterase activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Immunology
Min Zou, Qi-Shan Zeng, Jiao Nie, Jia-Hui Yang, Zhen-Yi Luo, Hua-Tian Gan
Summary: Inflammatory bowel disease (IBD) is a complex disorder involving genetic susceptibility, gut microbiota imbalance, mucosal immune disorder, and environmental factors. Recent studies have shown associations between ubiquitination and deubiquitination in the pathogenesis of IBD, highlighting the importance of these post-translational modifications in inflammation development and potential targeted therapeutics for IBD.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Chemistry, Medicinal
Yeon Jung Kim, Yeonjoo Lee, Hyungkyung Shin, SuA Hwang, Jinyoung Park, Eun Joo Song
Summary: This article summarizes the recently described components of the ubiquitin-proteasome system (UPS), including E3 ubiquitin ligases, deubiquitinases (DUBs), and immunoproteasomes, whose malfunction leads to tumorigenesis. The inhibitors of these components have been investigated in clinical trials as anticancer therapy since 2020. The article explains the mechanism and effects of several inhibitors in depth to better understand the advantages of targeting UPS components for cancer treatment. It also describes attempts to overcome resistance and limited efficacy of some launched proteasome inhibitors, as well as an emerging PROTAC-based tool for targeting UPS components in anticancer therapy.
ARCHIVES OF PHARMACAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Stephanie Diaz, Kankan Wang, Benita Sjogren, Xing Liu
Summary: Maintenance of protein homeostasis is crucial for eukaryotic biology, and the ubiquitin-proteasome system (UPS) plays an important role in the pathogenesis of cardiovascular diseases. Recent research has found that cullin-RING ubiquitin ligases (CRLs), an essential component of UPS, have significant physiological and pathological functions in the cardiovascular system.
Article
Neurosciences
Na Liu, Miao-Miao Lin, Yan Wang
Summary: Despite the increasing incidence and prevalence of neurodegenerative diseases, effective treatment strategies are lacking. This systematic literature review explores the involvement of E3 ubiquitin ligases and deubiquitinating enzymes in the pathogenesis mechanisms of these diseases, aiming to identify promising therapeutic targets.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Clemens Cammann, Nicole Israel, Hortense Slevogt, Ulrike Seifert
Summary: This review discusses the central role of T cell activation and the regulatory mechanisms involved, including protein phosphorylation and dephosphorylation, as well as the functions of E3 ligases and deubiquitinating enzymes. Furthermore, the importance of ubiquitination in T cell tolerance and the development of autoimmune diseases is highlighted, and new approaches for therapeutic intervention are explored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Yi Xiong, Chao Yu, Qianting Zhang
Summary: This review discusses the functions of ubiquitin proteasome system (UPS) components in mammalian spermatogenesis, including the composition of proteasome isoforms at each stage, the specificity and associated degradation events of each isoform, E3 ubiquitin ligases mediating protein ubiquitination, and the deubiquitinases involved in spermatogenesis and male fertility. Exploring the UPS machineries in spermatogenesis provides insights into protein dynamics during male germ cell production and sheds light on the etiology and pathogenesis of human male infertility.
Review
Virology
Lauren R. Combs, Jacob Combs, Robert McKenna, Zsolt Toth
Summary: This review focuses on how the KSHV protein RTA hijacks the host's ubiquitin-proteasome pathway to promote lytic reactivation and suppress the host's immune response. RTA targets transcription repressors and immune activators to block the lytic cycle of the virus.
Review
Cell Biology
Jason Q. Tang, Mary M. Marchand, Gianluca Veggiani
Summary: Protein turnover, regulated by the ubiquitin-proteasome system (UPS), is important for cellular homeostasis. Dysregulation of the UPS is associated with diseases and UPS enzymes are attractive therapeutic targets. However, redundancies of UPS enzymes make it challenging to identify precise drug targets. Engineered ubiquitin has emerged as a promising alternative to guide the development of small molecules targeting novel surfaces.
Review
Endocrinology & Metabolism
Shasha Shao, Daixing Zhou, Jun Feng, Yanyan Liu, Baturuhu, Huimei Yin, Daqian Zhan
Summary: Sepsis is a life-threatening organ dysfunction caused by an abnormal infection-induced immune response and remains a considerable therapeutic challenge. Immune-modulatory therapies have great potential for novel sepsis therapies by targeting the hyper-inflammation and late immunosuppression in sepsis patients. E3 ubiquitin ligases have been implicated in the regulation of immune response and may provide insights into the prevention and therapy for sepsis.
FRONTIERS IN ENDOCRINOLOGY
(2023)