Article
Biochemistry & Molecular Biology
Yuan Hu, Chenyang Qi, Jiaoyu Shi, Weiqiang Tan, Zhonghua Zhao, Yanyong Xu, Huijuan Wu, Zhigang Zhang
Summary: UCHL1 deficiency leads to severe kidney damage and proteinuria in podocytes, which is associated with ER stress, protein accumulation, and cell apoptosis. UCHL1 may be a potential target for preventing non-immune complex-mediated glomerulopathy.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Obstetrics & Gynecology
Meghan C. H. Ozcan, Lisa Cruz, Morgan F. F. Woodman, Fusun Gundogan, Kathryn J. J. Grive
Summary: The unique deubiquitinating enzyme UCHL1 regulates protein turnover only in oocytes, spermatogonia, and neurons. This study investigates the variation in UCHL1 expression across fetal maturation of oocytes to assess the lifelong ovarian reserve. The study found that UCHL1 expression in oocytes increases during ovarian development and reaches a plateau at 27 weeks gestational age, maintaining elevated levels until 36 weeks. This increase in expression is correlated with the increase in oocyte area, particularly during the transition of oocytes into primordial follicles.
REPRODUCTIVE SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Anna Sankiewicz, Tomasz Guszcz, Ewa Gorodkiewicz
Summary: The study investigates the relationship between the ubiquitin-proteasome system and transitional cell carcinoma, using SPRi-based biosensors to detect 20S proteasome and UCH-L1 in body fluids of TCC patients. The concentrations of both proteins were found to be significantly elevated in TCC patients compared to healthy subjects, suggesting their potential as cancer biomarkers.
APPLIED SCIENCES-BASEL
(2021)
Article
Biochemistry & Molecular Biology
Tomoo Suzuki, Yidan Dai, Masanori Ono, Junya Kojima, Toru Sasaki, Hiroshi Fujiwara, Naoaki Kuji, Hirotaka Nishi
Summary: Uterine leiomyomas, the most common pelvic tumors in women of reproductive age, can cause various symptoms and reproductive issues. This study found that UCHL1 expression is significantly higher in leiomyomas than in the myometrium. Inhibition of UCHL1 resulted in downregulation of COL1A1 and COL3A1 expression and decreased migration and contractility of leiomyoma cells. Targeting UCHL1 activity may be a potential therapeutic strategy for uterine leiomyoma.
Article
Biochemistry & Molecular Biology
Wenyan Yang, Shiqun Wang, Shengqiang Tong, Wei-Dong Zhang, Jiang-Jiang Qin
Summary: This article provides an overview of the ubiquitin-proteasome system (UPS) and its role in pancreatic cancer. Studies indicate that mutations or aberrant expression of UPS members can lead to rewriting of the ubiquitination code, affecting tumor growth, metastasis, immune evasion, and drug resistance. The article also reviews current UPS modulators and analyzes their potential as cancer therapies.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Thoa Kim Truong Huynh, Trinh Thi Thu Mai, Man Anh Huynh, Hideki Yoshida, Masamitsu Yamaguchi, Thao Thi Phuong Dang
Summary: This study demonstrates the impact of UCH-L1 deficiency on motor neuron health using a Drosophila model, highlighting the crucial role of UCH-L1 in neuronal health.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Cell Biology
Veronika Kinterova, Jiri Kanka, Alexandra Bartkova, Tereza Toralova
Summary: SCF-dependent proteolysis, mediated by SCF (Skp1-Cullin 1-F-box) ligases, plays a crucial role in cell cycle regulation, DNA repair, and centrosome cycle. It is also important in oogenesis and embryogenesis, with SCF beta TrCP and SCFSEL-10/FBXW7 being the most studied ligases in these processes. However, there are still many SCF ligases involved in embryogenesis that need to be further elucidated.
Article
Biophysics
Jinhee Lee, Bryant J. Kane, Mukund Khanwalker, Koji Sode
Summary: The incidence of traumatic brain injury (TBI) is increasing yearly, highlighting the importance of timely diagnosis for improved patient outcomes. In this study, a novel system for rapid and one-step electrochemical detection of ubiquitin C-terminal hydrolase L1 (UCHL1) was developed. The system demonstrated fast detection, no need for washing steps, and wide concentration range in artificial serum samples, making it a promising candidate for on-site TBI detection.
BIOSENSORS & BIOELECTRONICS
(2022)
Review
Oncology
Xiaowei Wang, Na Zhang, Meihua Li, Tao Hong, Wei Meng, Taohui Ouyang
Summary: Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a lesser-known member of the deubiquitinating enzyme family that has both deubiquitinase and ubiquitin ligase activity and plays a role in stabilizing ubiquitin. It was first discovered in the brain and is involved in regulating cell differentiation, proliferation, transcriptional regulation, and many other biological processes. UCH-L1 is predominantly expressed in the brain and has a role in tumor promotion or inhibition. The effect of UCH-L1 dysregulation in cancer and its underlying mechanisms are still debated. Extensive research into the role of UCH-L1 in different types of cancer is vital for future UCH-L1-associated cancer treatment. This review provides insights into the molecular structure and function of UCH-L1, summarizes its role in different types of cancer, and discusses how novel treatment targets contribute to cancer research.
Article
Pediatrics
Shuying Zeng, Yubo Huang, Tao Zhong, Tao Huang, Xianyan Dong, Huadong Zhu, Fulian Ouyang
Summary: This study found that the expression levels of serum UCH-L1 were significantly elevated in newborns with HIE, correlated with the severity of brain injury, and negatively associated with the development quotient, intelligence index, and NBNA score of newborns.
TRANSLATIONAL PEDIATRICS
(2021)
Review
Biochemistry & Molecular Biology
Jerry Vriend, Thatchawan Thanasupawat, Namita Sinha, Thomas Klonisch
Summary: The ubiquitin proteasome system plays a critical role in maintaining cellular homeostasis and impacting various functions in normal and cancer cells. This study reviewed the role of the UPS in ependymoma brain tumors and identified potential therapeutic targets specific to different subtypes of EPN. The study provides valuable insights into the cellular networks involved in EPN and suggests the UPS as a potential avenue for targeted therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Noha Hafez, Zahraa Modather El-Awadly, Reem K. Arafa
Summary: Researchers have highlighted the importance of ubiquitin in regulatory pathways, emphasizing its role in cell vitality, maturation, and differentiation. Deubiquitylating enzymes, especially UCH-L3, play crucial roles in maintaining cellular homeostasis and have been implicated in various molecular and cellular processes. The discovery of inhibitors for UCH-L3 through high throughput screening holds promise for cancer and neurodegenerative disease treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Vu Thuy Khanh Le-Trilling, Sofia Banchenko, Darius Paydar, Pia Madeleine Leipe, Lukas Binting, Simon Lauer, Andrea Graziadei, Robin Klingen, Christine Gotthold, Joerg Buerger, Thilo Bracht, Barbara Sitek, Robert Jan Lebbink, Anna Malyshkina, Thorsten Mielke, Juri Rappsilber, Christian M. T. Spahn, Sebastian Voigt, Mirko Trilling, David Schwefel
Summary: This study revealed that rat cytomegalovirus infection induces the loss of transcription factor STAT2, which is crucial for antiviral interferon signaling. It was found that viral protein E27 exploits the host-cell CRL4 complexes to degrade STAT2 through poly-ubiquitylation. Furthermore, structural analyses showed that E27 recruits STAT2 through a bipartite binding interface, partially overlapping with the IRF9 binding site.
Article
Cell Biology
Zhiping Mi, Steven H. Graham
Summary: This review focuses on the potential role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury and recovery. It discusses the normal physiological functions of UCHL1, the effects of posttranslational modification sites and splice variants on UCHL1 function, mouse models with UCHL1 mutations and deletions, and the hypothesized role and pathogenic mechanisms of UCHL1 in neurodegenerative diseases and brain injury.
AGEING RESEARCH REVIEWS
(2023)
Article
Multidisciplinary Sciences
Julia Reichelt, Wiebke Sachs, Sarah Froembling, Julia Fehlert, Maja Studencka-Turski, Anna Betz, Desiree Loreth, Lukas Blume, Susanne Witt, Sandra Pohl, Johannes Brand, Maire Czesla, Jan Knop, Bogdan I. Florea, Stephanie Zielinski, Marlies Sachs, Elion Hoxha, Irm Hermans-Borgmeyer, Gunther Zahner, Thorsten Wiech, Elke Krueger, Catherine Meyer-Schwesinger
Summary: In membranous nephropathy, autoantibodies target podocytes of the kidney filter, resulting in injury. The authors found that the disturbances in protein stability and proteinuria are related to abnormal interactions between non-functional UCH-L1 enzyme and the proteasome, reducing its capacity. The mechanistic significance of the ubiquitin proteasome system (UPS) in a kidney autoimmune environment is not well understood.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Luis Solabre Valois, Kevin A. Wilkinson, Yasuko Nakamura, Jeremy M. Henley
Review
Biochemistry & Molecular Biology
Jeremy M. Henley, Richard Seager, Yasuko Nakamura, Karolina Talandyte, Jithin Nair, Kevin A. Wilkinson
Summary: SUMOylation is a post-translational modification that regulates protein signaling by adjusting conformation or interactions; recent research has shown that SUMOylation of extranuclear proteins contributes to neuronal development, stress responses and synaptic transmission regulation.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Vanilla (Hua) Shi, Tim J. Craig, Paul Bishop, Yasuko Nakamura, Dan Rocca, Kevin A. Wilkinson, Jeremy M. Henley
Summary: This study reveals that CK2α over-expression reduces evoked synaptic vesicle release, while knockdown of CK2α enhances vesicle exocytosis from the reserve pool, and a phosphorylation-deficient mutant also increases vesicle exocytosis, indicating a previously unsuspected role of CK2α phosphorylation in regulating the reserve synaptic vesicle pool.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Neurosciences
Hiago Murilo Melo, Cristiane Ribeiro de Carvalho, Alexandre Ademar Hoeller, Jefferson Luiz Brum Marques, Marcelo Neves Linhares, Mark William Lopes, Guilherme Loureiro Fialho, Peter Wolf, Katia Lin, Zuner A. Bortolotto, Jeremy M. Henley, Andre D'Avila, Rodrigo Bainy Leal, Roger Walz
Summary: The study investigated the association between HRV and neurochemistry biomarkers of synaptic plasticity in the limbic system structures. Results showed a negative association between the levels of P-GluA1-Ser845 in AMY and resting HRV in MTLE-HS. The findings suggest that specific changes in synaptic plasticity may impact the regulation of the brain-heart axis by the limbic system.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Neurosciences
Jithin D. Nair, Kevin A. Wilkinson, Jeremy M. Henley, Jack R. Mellor
Summary: This article reviews the roles of kainate receptors in synaptic plasticity, focusing on their impact on postsynaptic signaling and presynaptic auto-receptor functions. It also explores the plasticity of kainate receptors themselves and their contribution to synaptic transmission plasticity.
Review
Neurosciences
Jeremy M. Henley, Jithin D. Nair, Richard Seager, Busra P. Yucel, Gavin Woodhall, Benjamin S. Henley, Karolina Talandyte, Hope I. Needs, Kevin A. Wilkinson
Summary: Epilepsy is caused by abnormal neuronal network activity. The review focuses on the role and regulation of kainate and AMPA receptors in seizure activity, discussing the impact of GluK2 and GluA2 subunits on their respective receptors' properties.
Review
Biology
Hope I. Needs, Margherita Protasoni, Jeremy M. Henley, Julien Prudent, Ian Collinson, Goncalo C. Pereira
Summary: Mitochondrial protein import is crucial for normal organelle physiology, and impaired import can lead to defective mitochondrial respiration and various diseases. Activation of stress response pathways is necessary to overcome dysfunction and restore proteostasis in mitochondria and cells.
Article
Biology
Kirsty J. McMillan, Paul J. Banks, Francesca L. N. Hellel, Ruth E. Carmichael, Thomas Clairfeuille, Ashley J. Evans, Kate J. Heesom, Philip Lewis, Brett M. Collins, Zafar Bashir, Jeremy M. Henley, Kevin A. Wilkinson, Peter J. Cullen
Summary: SNX27 is associated with various neuropathologies by sorting integral proteins to the synaptic surface, particularly AMPA receptors. Through regulating the endosomal sorting of LRFN2, SNX27 indirectly controls AMPA receptor-mediated synaptic transmission and plasticity, shedding light on their perturbed functions in neurological conditions.
Article
Multidisciplinary Sciences
Jithin D. Nair, Ellen Braksator, Busra P. Yucel, Alexandra Fletcher-Jones, Richard Seager, Jack R. Mellor, Zafar Bashir, Kevin A. Wilkinson, Jeremy M. Henley
Summary: The study found that sustained activation of GluK2 subunit-containing kainate receptors leads to AMPAR endocytosis and induces LTD in hippocampal neurons. In acute hippocampal slices, kainate application causes a significant loss of GluA2-containing AMPARs from synapses and long-lasting depression of AMPAR excitatory postsynaptic currents in CA1. These results demonstrate that kainate receptors can bidirectionally regulate synaptic AMPARs and synaptic plasticity via different signaling pathways.
Article
Neurosciences
Luis Solabre Valois, Vanilla (Hua) Shi, Paul Bishop, Bangfu Zhu, Yasuko Nakamura, Kevin A. Wilkinson, Jeremy M. Henley
Summary: The non-toxic C-terminal region of BoNT/A's receptor-binding domain, HCC/A, activates Rac1 and ERK pathway to enhance axonal outgrowth, dendritic protrusion formation, and synaptic vesicle release in hippocampal neurons. These data suggest that HCC/A may have neurotrophic properties independently of BoNT catalytic activity or toxicity.
IBRO NEUROSCIENCE REPORTS
(2021)
Article
Cell Biology
Chun Guo, Keri L. Hildick, Juwei Jiang, Alice Zhao, Wenbin Guo, Jeremy M. Henley, Kevin A. Wilkinson
Summary: Inhibition of Drp1 SUMOylation enhances its interaction with Bcl-x(L) and promotes cell death, while SENP3-mediated deSUMOylation facilitates the Mff-primed Drp1-Bcl-x(L) interaction that contributes to cell death following ischemia.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Hope I. Needs, Kevin A. Wilkinson, Jeremy M. Henley, Ian Collinson
Summary: Mitochondrial protein import is essential for organellar biogenesis and ATP supply. This study reveals that the aggregation-prone Tau variant reduces the levels of components of the import machinery, but does not affect protein import or respiratory function. Instead, it induces the formation of tunnelling nanotubes (TNTs) potentially for the recruitment or disposal of mitochondria. These findings suggest a link between Tau aggregation and defective mitochondrial import relevant to disease.
JOURNAL OF CELL SCIENCE
(2023)
Article
Neurosciences
Busra P. Yucel, Enaam M. Al Momany, Ashley J. Evans, Richard Seager, Kevin A. Wilkinson, Jeremy M. Henley
Summary: The palmitoylation of GluK2 contributes to stabilizing the surface expression of KARs, while dynamic depalmitoylation promotes downstream phosphorylation and SUMOylation to mediate activity-dependent KAR endocytosis.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Jithin D. Nair, Kevin A. Wilkinson, Busra P. Yucel, Christophe Mulle, Bryce Vissel, Jack Mellor, Jeremy M. Henley
Summary: Editing of GluK2 Q/R influences the synaptic expression and plasticity of AMPARs by modulating the ionotropic/metabotropic balance of KAR signaling.
Article
Biochemical Research Methods
Jithin D. Nair, Jeremy M. Henley, Kevin A. Wilkinson
Summary: The surface biotinylation technique is used to label surface-expressed proteins in primary neuronal cultures, allowing for isolation and measurement of protein levels through pull-down with streptavidin beads and western blotting. This approach has been used to monitor changes in AMPAR and KAR subunits, but can be adapted for investigating any surface-expressed protein.
