Article
Cell Biology
Cyriel Sebastiaan Olie, Adan Pinto-Fernandez, Andreas Damianou, Iolanda Vendrell, Hailiang Mei, Bianca den Hamer, Erik van der Wal, Jessica C. de Greef, Vered Raz, Benedikt M. Kessler
Summary: The ubiquitin proteasomal system plays a critical role in muscle physiology, but the function of deubiquitinating enzymes (DUBs) in muscle cells remains poorly understood. Through a genetic screen, we discovered that the depletion of USP18, a DUB, affects muscle cell differentiation. USP18 regulates differentiation initiation and maintenance independently of ISG15 and the ISG response. Alterations in gene networks and protein expression profiles were observed in the absence of USP18, leading to disrupted calcium homeostasis and reduced contractile force.
CELL DEATH & DISEASE
(2023)
Review
Pharmacology & Pharmacy
Laura D. Carreira, Rita I. Oliveira, Vania M. Moreira, Jorge A. R. Salvador
Summary: This review summarizes the structure and function of USP7, its relevance in cancer, and the recent advances and future perspectives in the development of USP7 inhibitors for cancer therapy.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Review
Cell Biology
Xiaolong Li, Ge Yang, Wenyao Zhang, Biying Qin, Zifan Ye, Huijing Shi, Xinmeng Zhao, Yihang Chen, Bowei Song, Ziqing Mei, Qi Zhao, Feng Wang
Summary: This article provides an overview of the recent advances in the structure and function of USP13, its relationship with diseases, and the discovery and development of inhibitors. These studies contribute to a better understanding of the molecular mechanisms of USP13 and facilitate the development of more potent inhibitors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Feng Wang, Yu Gao, Lihui Zhou, Junhao Chen, Zhiyan Xie, Zifan Ye, Yanfeng Wang
Summary: USP30 is a deubiquitinating enzyme localized in mitochondria and peroxisomes, playing essential roles in various cellular events. Dysregulation of USP30 is associated with physiological disorders, and research on USP30 inhibitors shows promise for potential therapeutic applications, especially in treating pulmonary disorders.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jun-O Jin, Nidhi Puranik, Quyen Thu Bui, Dhananjay Yadav, Peter Chang-Whan Lee
Summary: The ubiquitin system plays a crucial role in regulating cellular protein processes and abnormalities in ubiquitin modulation can lead to various cancers, with changes in protein ubiquitination contributing to lung cancer development. Inhibitors targeting the ubiquitin system have been developed for clinical applications in lung cancer treatment, highlighting the potential of this therapeutic approach.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Feng Wang, Shuo Ning, Beiming Yu, Yanfeng Wang
Summary: Ubiquitin-specific protease 14 (USP14) is an enzyme involved in regulating protein degradation and is associated with various diseases and cellular processes. Its activity is tightly regulated through conformational changes and phosphorylation. USP14 has gained significant interest as a therapeutic target due to its role in stabilizing disease-causing proteins and oncology targets.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Lukas Wettstein, Frank Kirchhoff, Jan Muench
Summary: TMPRSS2 is a crucial protease with widespread expression in various organs, playing a role in the entry processes of different respiratory viruses. Inhibiting TMPRSS2 activity is a promising strategy for blocking viral infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)
Article
Immunology
Justin D. Shepard, Brendan T. Freitas, Sergio E. Rodriguez, Florine E. M. Scholte, Kailee Baker, Madelyn R. Hutchison, Jaron E. Longo, Holden C. Miller, Brady M. O'Boyle, Aarushi Tandon, Peng Zhao, Neil J. Grimsey, Lance Wells, Eric Bergeron, Scott D. Pegan
Summary: Post-translational modification of host and viral proteins by ubiquitin and ubiquitin-like proteins is important for the host's immune response. Avian species lack an ubiquitin-like protein (ISG15) found in mammals and other reptiles, raising interest in studying the structure and function of avian OASL.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Medicinal
Duaa Kanan, Tarek Kanan, Berna Dogan, Muge Didem Orhan, Timucin Avsar, Serdar Durdagi
Summary: USP7 has been identified as a promising target for cancer therapy, and this study successfully identified and validated 7 potential USP7 inhibitors through computational methods and in vitro enzymatic inhibition assays.
Review
Plant Sciences
Gautier Langin, Manuel Gonzalez-Fuente, Suayib Uestuen
Summary: The plant immune system detects pathogens and activates defense responses, while pathogens manipulate the host's ubiquitin-proteasome system to promote disease.
ANNUAL REVIEW OF PHYTOPATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nicholas W. Ashton, Gabrielle J. Valles, Nancy Jaiswal, Irina Bezsonova, Roger Woodgate
Summary: USP7 is a critical deubiquitinating enzyme with important roles in multiple signaling pathways. The study reveals that DNA polymerase iota is a novel substrate of USP7, which requires binding to both TRAF and UBL1-2 domains for efficient deubiquitination. This discovery establishes a new bipartite mode of substrate binding for USP7.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Xiaodi Du, Hongyu Song, Nengxing Shen, Ruiqi Hua, Guangyou Yang
Summary: Ubiquitin-conjugating enzymes (E2s) play a vital role in connecting ubiquitin chains to target proteins, regulating the stability and activity of substrate proteins, and participating in various biological processes. Studies have suggested their potential as therapeutic targets in cancer, leading to a need for further exploration of their molecular basis and development of effective drugs targeting E2s.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cardiac & Cardiovascular Systems
Wei Zhao, Xiuying Zhang, Jianhui Rong
Summary: Myocardial infarction is a prevalent and life-threatening cardiovascular disease with interventional therapies mainly focusing on restoring coronary reperfusion. Recently discovered SUMOylation is crucial in regulating cardiac functions and potentially targeting it could provide treatments against myocardial injury. Understanding the effects of SUMOylation in the pathophysiology of myocardial infarction suggests it as a key therapeutic target for treating cardiovascular diseases.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Parasitology
Nandita Tanneru, M. Angel Nivya, Navin Adhikari, Kanika Saxena, Zeba Rizvi, Renu Sudhakar, Amit Kumar Nagwani, Atul, Faisal Mohammed Abdul Al-Nihmi, Kota Arun Kumar, Puran Singh Sijwali
Summary: DDI1 protein is involved in various cellular processes and has distinct domains that confer different activities. It is a potential target for HIV protease inhibitors and plays a role in parasite development.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2023)