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
Chenxiao Zheng, Jiayi Chen, Yurui Wu, Xiaochao Wang, Yongan Lin, Lilu Shu, Wenjun Liu, Peter Wang
Summary: Osteoarthritis is a non-inflammatory degenerative joint arthritis that worsens disability in the elderly. Ubiquitination, a type of post-translational modification, has been shown to impact the development and progression of osteoarthritis by targeting specific proteins for ubiquitination and influencing protein stability and localization. This review summarizes the multifaceted role of E3 ubiquitin ligases and deubiquitinases in the pathogenesis of osteoarthritis, as well as highlighting compounds that target these proteins to influence disease progression. The modulation of ubiquitination and deubiquitination may hold promise for improving treatment outcomes in osteoarthritis patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Fabiana Alejandra Rossi, Mario Rossi
Summary: This article summarizes the role of deubiquitinating enzyme USP19 in controlling various cellular processes in different tumors, and its potential as a therapeutic target in oncology.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Microbiology
Vera Vozandychova, Pavla Stojkova, Kamil Hercik, Pavel Rehulka, Jiri Stulik
Summary: Ubiquitination, similar to phosphorylation and acetylation, plays a crucial role in regulating various cell processes. Understanding how pathogens manipulate host ubiquitination processes is important for vaccine development and disease treatment. Pathogenic bacteria encode effector proteins targeting the host ubiquitin machinery to disrupt host defense processes.
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
Genetics & Heredity
Xiaofeng Dai, Tongxin Zhang, Dong Hua
Summary: Ubiquitination and SUMOylation are essential components of the ubiquitination-proteasome system, playing central roles in cancer initiation and development. Researchers are still exploring how to precisely harness the ubiquitination-proteasome system in cancer control, while the seemingly redundant roles of ubiquitination and SUMOylation complicate the understanding of their roles in carcinogenesis. This review sheds light on the similarities and differences of ubiquitination and SUMOylation, forecasting novel onco-therapeutic opportunities through cell homeostasis control.
Article
Genetics & Heredity
Nicolaj Jeran, Lisa Rotasperti, Giorgia Frabetti, Anna Calabritto, Paolo Pesaresi, Luca Tadini
Summary: During a plant's life cycle, plastids undergo various modifications, and plastid proteome rearrangements, protein homeostasis, and communication pathways are crucial for proper plastid differentiation and functioning. The study on Arabidopsis gun1-102 ftsh5-3 mutants revealed the significant role of PUB4 E3 ubiquitin ligase in degrading damaged chloroplasts, contributing to the variegated phenotype in seedlings.
Review
Pharmacology & Pharmacy
Yanfeng Wang, Feng Wang
Summary: Post-translational modifications like ubiquitination play crucial roles in regulating biological processes in eukaryotes, with DUBs being key enzymes that control ubiquitin-related pathways. Dysregulation of DUBs can lead to various diseases. Phosphorylation is the most extensively studied post-translational modification of DUBs, influencing their function and activity.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Elham Aryapour, Thomas Kietzmann
Summary: Liver diseases such as NAFLD, NASH, and HCC are associated with dysregulation of hepatic mitophagy. The involvement of mitochondrial E3 ubiquitin ligases and DUBs in the degradation of mitochondrial proteins and proper execution of mitophagy process makes them potential biomarkers and therapeutic targets for liver diseases.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Cell Biology
Longhao Wang, Tao Hu, Zhibo Shen, Yuanyuan Zheng, Qishun Geng, Lifeng Li, Beibei Sha, Miaomiao Li, Yaxin Sun, Yongjun Guo, Wenhua Xue, Dan Xuan, Ping Chen, Jie Zhao
Summary: The study revealed that targeting the deubiquitinating enzyme USP1 may be a potential strategy for the treatment of hepatocellular carcinoma (HCC). The USP1 inhibitor ML-323 inhibited the growth of HCC cells and induced cell cycle arrest. ML-323 treatment resulted in the accumulation of ubiquitinated proteins, induction of endoplasmic reticulum stress, and Noxa-dependent apoptosis. Additionally, active endoplasmic reticulum stress induced protective autophagy through AMPK phosphorylation.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Chunyi Liu, Thomas Jursa, Michael Aschner, Donald R. Smith, Somshuvra Mukhopadhyay
Summary: This study elucidated a fundamental protective response mechanism to manganese toxicity, in which elevated levels of manganese activate HIF1 and HIF2 to up-regulate the expression of SLC30A10, thereby reducing cellular and organismal manganese levels. This suggests the potential repurposing of prolyl hydroxylase inhibitors for the management of manganese neurotoxicity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Xianglan Yi, Mengxin Qi, Mingxiang Huang, Sheng Zhou, Jing Xiong
Summary: The study demonstrated that honokiol (HNK) inhibits HIF-1 alpha-mediated glycolysis and the progression of human breast cancer. HNK reduces glucose uptake and lactate production, and increases oxygen consumption in breast cancer cells. Additionally, HNK downregulates the expression of HIF-1 alpha and its downstream regulators.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Plant Sciences
Marco Trujillo
Summary: Microbial attack is detected by immune receptors at the plasma membrane, triggering signaling cascades leading to immune response. Ubiquitin and ubiquitin-like protein modifiers play key roles in controlling signaling intensity and buffering proteome imbalances caused by pathogen attack. Recent advances have revealed a complex signaling circuitry regulating cellular dynamics and protein degradation to maintain homeostasis.
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)
Article
Biochemistry & Molecular Biology
Wenguang He, Sarah Batty-Stuart, Jeffrey E. Lee, Michael Ohh
Summary: The study demonstrates that both hydroxyprolines in HIF-1 alpha ODD bind to the same interface on VHL with similar affinity; VHL binding affinity to ODD remains relatively unchanged whether one or two hydroxyprolines are present; ODD with two hydroxyprolines can accommodate two VHLs, and the ubiquitination rate is comparable between ODD with one or two hydroxyprolines. However, the two hydroxyprolines show distinct contributions to the intracellular stability of HIF-1 alpha ODD.
JOURNAL OF MOLECULAR BIOLOGY
(2021)