Review
Oncology
Matthew P. Parker, Kenneth R. Peterson, Chad Slawson
Summary: O-linked beta-N-acetylglucosamine (O-GlcNAc) is a post-translational modification linking nutrient flux to gene transcription. Aberrant O-GlcNAcylation is associated with cancer development, progression, and alterations in gene expression. O-GlcNAc cycling by OGT and OGA regulates various aspects of gene expression, including RNA polymerase function and transcription factor activity.
Article
Biochemistry & Molecular Biology
Adam Kositzke, Dacheng Fan, Ao Wang, Hao Li, Matthew Worth, Jiaoyang Jiang
Summary: The essential human enzyme O-Linked beta-N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) play important roles in modifying intracellular proteins. Screening OGT TPR mutants revealed key residues affecting OGA O-GlcNAcylation. This study is the first to systematically investigate each OGT TPR, providing insights into the binding mechanism of OGT to OGA protein substrates.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Biochemistry & Molecular Biology
Rodrigo P. Silva-Aguiar, Diogo B. Peruchetti, Ana Acacia S. Pinheiro, Celso Caruso-Neves, Wagner B. Dias
Summary: Kidneys maintain internal stability by regulating body fluid composition through the correlation between structure and function in the nephron. Kidney diseases have a global impact on healthcare programs, and there are limited treatment options available. Protein O-GlcNAcylation, a post-translational modification involved in regulating various cell functions, is associated with the development of chronic degenerative diseases and has implications in cardiovascular, neurodegenerative, and metabolic diseases. This review discusses the impact of protein O-GlcNAcylation on renal function, disease conditions, and future directions in the field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Agriculture, Dairy & Animal Science
Laila T. Kirkpatrick, Morgan R. Daughtry, Samer El-Kadi, Tim Hao Shi, David E. Gerrard
Summary: This study investigates the role of O-GlcNAcylation in porcine myogenesis. The findings show that elevated O-GlcNAcylation impairs muscle cell differentiation by downregulating the expression of myogenin and inhibiting Akt phosphorylation. In contrast, inhibition of O-GlcNAc transferase has little impact on myoblast proliferation or differentiation. Additionally, the study demonstrates that O-GlcNAcylation plays a critical role in muscle regeneration in vivo. These findings suggest that O-GlcNAcylation serves as a nutrient sensor and regulates muscle growth in agriculturally important animals.
JOURNAL OF ANIMAL SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Jiahui He, Zhiya Fan, Yinping Tian, Weiwei Yang, Yichao Zhou, Qiang Zhu, Wanjun Zhang, Weijie Qin, Wen Yi
Summary: Light control of OGT activity in cells has been achieved by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine, providing a valuable chemical tool to control cellular O-GlcNAc with spatiotemporal precision and aiding in a better understanding of O-GlcNAc function.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Oncology
Chia-Wei Hu, Jinshan Xie, Jiaoyang Jiang
Summary: Dynamic O-GlcNAc modification plays a crucial role in regulating protein functions in various cellular processes. Abnormal regulation of the enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), as well as changes in cellular O-GlcNAc profiles, are common features in almost all types of cancer. Recent studies have focused on the structural features of OGT and OGA, as well as their aberrant protein-protein interactions (PPIs) and their role in rewiring cancer networks. Understanding these interactions and mechanisms will help identify key proteins and modules that drive malignancies, and potentially lead to new directions for anti-cancer drug development.
Article
Biochemistry & Molecular Biology
Patrick Weber, Zuzana Meszaros, Pavla Bojarova, Manuel Ebner, Roland Fischer, Vladimir Kren, Natalia Kulik, Philipp Mueller, Miluse Vlachova, Kristyna Slamova, Arnold E. Stuetz, Martin Thonhofer, Ana Torvisco, Tanja M. Wrodnigg, Andreas Wolfsgruber
Summary: A new class of compounds that inhibit the de-O-glycosylation of proteins has been discovered. These compounds, highly substituted diaminocyclopentanes, are selective and reversible inhibitors of O-beta-N-acetyl-D-glucosaminidase (O-GlcNAcase), and show impressive biological activities. They could serve as promising leads for the development of anti-tau-phosphorylation agents to potentially ameliorate Alzheimer's disease.
BIOORGANIC CHEMISTRY
(2023)
Article
Clinical Neurology
Sang-Min Kim, Seungjae Zhang, Jiwon Park, Hyun Jae Sung, Thuy-Duong Thi Tran, ChiHye Chung, Inn-Oc Han
Summary: REM sleep deprivation in mice is linked to impaired contextual fear memory and reduced hexosamine biosynthetic pathway/O-GlcNAc flux in the brain. Modulating O-GlcNAc cycling restores cognitive deficits induced by REMSD, highlighting a molecular link between sleep and cognitive function. This study provides comprehensive evidence of dynamic O-GlcNAcylation changes during the learning and memory process in mice.
Article
Multidisciplinary Sciences
Akihito Ishikita, Shouji Matsushima, Soichiro Ikeda, Kosuke Okabe, Ryohei Nishimura, Tomonori Tadokoro, Nobuyuki Enzan, Taishi Yamamoto, Masashi Sada, Yoshitomo Tsutsui, Ryo Miyake, Masataka Ikeda, Tomomi Ide, Shintaro Kinugawa, Hiroyuki Tsutsui
Summary: The molecular mechanisms of cardiac hypertrophy induced by glucose metabolism remain incompletely understood. The Hexosamine biosynthesis pathway (HBP) plays a key role in mediating cardiac hypertrophy through protein O-GlcNAcylation and Akt activation. GFAT2, a critical enzyme in the HBP pathway, is identified as a major isoform in the heart and is involved in regulating cardiomyocyte hypertrophy.
Article
Biochemistry & Molecular Biology
Sheng Yan, Bin Peng, Shifeng Kan, Guangcan Shao, Zhikai Xiahou, Xiangyan Tang, Yong-Xiang Chen, Meng-Qiu Dong, Xiao Liu, Xingzhi Xu, Jing Li
Summary: This article investigates the impact of O-GlcNAc transferase (OGT) on PLK1, and finds that OGT can modify PLK1 through O-GlcNAcylation. Further research reveals that the T291A and T291N mutations increase the stability of PLK1 and lead to chromosome segregation defects and uterine carcinoma. The findings suggest that OGT exerts its mitotic function partially through O-GlcNAcylation of PLK1, which may contribute to tumorigenesis by elevating O-GlcNAc levels.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Israel Olapeju Bolanle, Kirsten Riches-Suman, Ritchie Williamson, Timothy M. Palmer
Summary: Protein O-GlcNAcylation has emerged as a new mechanism in the pathogenesis of cardiovascular diseases, playing a vital role in modulating vascular homeostasis and cardiac function through altering cellular functions of target proteins. Studying this mechanism may provide new therapeutic targets for the development of more effective medicines.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Chia-Hung Lin, Chen-Chung Liao, Mei-Yu Chen, Teh-Ying Chou
Summary: This study investigates the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells, revealing that OGA expression is regulated at the mRNA level while OGT expression is controlled through translation. The research also highlights the important role of 4E-BP1 in maintaining intracellular O-GlcNAc levels homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Ramkumar Mohan, Seokwon Jo, Elina Da Sol Chung, Eunice Oribamise, Amber Lockridge, Juan E. Abrahante-Llorens, Hai-Bin Ruan, Xiao-Yong Yang, Emilyn U. Alejandro
Summary: The study revealed that beta-cell Ogt overexpression in mice led to glucose intolerance under metabolic stressors such as high-fat diet and streptozocin, despite normal insulin secretion and beta-cell mass. Additionally, female mice with beta Ogt overexpression developed hyperglycemia and glucose intolerance post-treatment with streptozocin, contrary to the typical resistance seen in female mice. Transcriptional analysis showed common altered pathways involving pro-survival and inflammatory regulators in islets with loss or gain of Ogt. These findings suggest a gene dosage effect of Ogt and highlight the importance of O-GlcNAc cycling in beta-cell survival and function for glucose homeostasis.
Article
Biochemistry & Molecular Biology
Yun Ge, Hailin Lu, Bo Yang, Christina M. Woo
Summary: The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. O-GlcNAc levels in cells can dynamically respond to environmental cues in a temporal and spatial manner, leading to altered signal transduction and functional effects. In this study, the researchers developed a strategy for controlling the levels of O-GlcNAc in live cells based on the design of an O-GlcNAcase (OGA) fused to an intein triggered by 4-hydroxytamoxifen (4-HT).
ACS CHEMICAL BIOLOGY
(2023)
Article
Oncology
Di Wang, Jiaan Wu, Dandan Wang, Xiaoyan Huang, Naining Zhang, Yikang Shi
Summary: The study demonstrates that cisplatin enhances protein O-GlcNAcylation by altering the activity of OGT, OGA, and AMPK in lung cancer cells both in vitro and in vivo. The findings also show that cisplatin treatment results in increased global protein O-GlcNAc levels, upregulated expression of OGT and OGA, and inhibited AMPK activity in the cells. Additionally, decreased AMPK activation inhibits GFAT1 phosphorylation and promotes its activity, leading to elevated UDP-GlcNAc production.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2021)
Article
Biochemical Research Methods
Hannah M. Stephen, Jeremy L. Praissman, Lance Wells
Summary: The O-GlcNAc transferase (OGT) selectively modifies proteins with beta-N-acetyl-glucosamine, and the TPR domain of OGT plays a role in substrate selection. Variants of OGT causing X-linked intellectual disability (XLID) occur in the TPR domain. Identified TPR interactors of OGT are associated with disease states, particularly intellectual disability, providing a starting point for further research on the role of OGT in cellular processes and disease mechanisms.
JOURNAL OF PROTEOME RESEARCH
(2021)
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
Multidisciplinary Sciences
M. Osman Sheikh, Chantelle J. Capicciotti, Lin Liu, Jeremy Praissman, Dahai Ding, Daniel G. Mead, Melinda A. Brindley, Tobias Willer, Kevin P. Campbell, Kelley W. Moremen, Lance Wells, Geert-Jan Boons
Summary: Matriglycan plays a critical role in protein binding and viral infection, and its length can be adjusted accordingly. This finding contributes to a better understanding of the interaction between cells and viruses.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Trevor M. Adams, Peng Zhao, Digantkumar Chapla, Kelley W. Moremen, Lance Wells
Summary: N-glycosylation is an essential posttranslational modification in eukaryotic cells that affects various properties of glycoproteins. This study found that local steric and electrostatic factors surrounding each glycosylation site influence the availability and efficiency of glycan modification, leading to the formation of microheterogeneity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Pedro Monagas-Valentin, Robert Bridger, Ishita Chandel, Melissa Koff, Boris Novikov, Patrick Schroeder, Lance Wells, Vladislav Panin
Summary: Mutations in POMTs cause brain defects and muscular dystrophies due to abnormal glycosylation of alpha-Dg. PTP69D is identified as a gene that interacts with POMTs to produce the abdomen rotation phenotype. PTP69D is required for larval sensory axon wiring and is a substrate of POMT-mediated O-mannosylation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Jeremy D. DeBarry, Mustafa V. Nural, Suman B. Pakala, Vishal Nayak, Susanne Warrenfeltz, Jay Humphrey, Stacey A. Lapp, Monica Cabrera-Mora, Cristiana F. A. Brito, Jianlin Jiang, Celia L. Saney, Allison Hankus, Hannah M. Stealey, Megan B. DeBarry, Nicolas Lackman, Noah Legall, Kevin Lee, Yan Tang, Anuj Gupta, Elizabeth D. Trippe, Robert R. Bridger, Daniel Brent Weatherly, Mariko S. Peterson, Xuntian Jiang, ViLinh Tran, Karan Uppal, Luis L. Fonseca, Chester J. Joyner, Ebru Karpuzoglu, Regina J. Cordy, Esmeralda V. S. Meyer, Lance L. Wells, Daniel S. Ory, F. Eun-Hyung Lee, Rabindra Tirouvanziam, Juan B. Gutierrez, Chris Ibegbu, Tracey J. Lamb, Jan Pohl, Sarah T. Pruett, Dean P. Jones, Mark P. Styczynski, Eberhard O. Voit, Alberto Moreno, Mary R. Galinski, Jessica C. Kissinger
Summary: This study presents methods and data generated from longitudinal systems biology infection experiments to investigate the biology, pathogenesis, and immune responses of Plasmodium cynomolgi. The findings provide important insights into the parasite species and serve as a reliable data resource.
Meeting Abstract
Biochemistry & Molecular Biology
Trevor M. Adams, Peng Zhao, Digantkumar Chapla, Kelley W. Moremen, Lance Wells
Meeting Abstract
Biochemistry & Molecular Biology
Russell Gotschall, Jonathan Roberts, Kylie Gray, Linda Lyons, Riley Marcincyk, Udayanga Wanninayake, Annie Arnold, Lydia Gotschall, Vaughn Weaver, Peng Zhao, Lance Wells, Lin Liu, Hung Do, Michael DiGruccio
Meeting Abstract
Biochemistry & Molecular Biology
Paige LaMore, Ye Ji, Oliver C. Grant, Jeremy Praissman, Digantkumar Chapla, Annapoorani Ramiah, Kelley Moremen, Lance Wells, Robert J. Woods
Meeting Abstract
Biochemistry & Molecular Biology
Pedro Monagas-Valentin, Robert Bridger, Ishita Chandel, Melissa Koff, Boris Novikov, Patrick Schroeder, Lance Wells, Vladislav Panin
Meeting Abstract
Biochemistry & Molecular Biology
Ashley M. Rogers, Robert T. Patry, Harald Nothaft, Robert Bridger, Lauren Pepi, Asif Shajahan, Parastoo Azadi, Lance Wells, Christine M. Szymanski
Meeting Abstract
Biochemistry & Molecular Biology
Lance Wells
Article
Biochemistry & Molecular Biology
Michael E. Rusiniak, Patrick R. Punch, Nitai C. Hait, Aparna Maiti, Robert T. Burns, Digantkumar Chapla, Kelley W. Moremen, Peng Zhao, Lance Wells, Karin Hoffmeister, Joseph T. Y. Lau
Summary: Interaction between immune cells and the systemic environment is crucial for the coordinated development and execution of immune responses. This study reveals that extracellular ST6GAL1 plays a profound role in monocyte-macrophage lineage cells, promoting cell development and survival by activating essential cell surface receptors and initiating intracellular signaling.
Review
Biochemistry & Molecular Biology
Hannah M. Stephen, Trevor M. Adams, Lance Wells
Summary: This review discusses the importance of O-GlcNAc modification in intracellular processes and various diseases, as well as explores the substrate selection mechanisms for O-GlcNAc cycling. Current research paints a picture of an exquisitely regulated and complex system by which OGT and OGA select substrates.
Review
Biochemical Research Methods
Jeremy L. Praissman, Lance Wells
Summary: The outbreak of the coronavirus in 2019 led to a rapid and robust response from the global scientific and medical communities, resulting in a large number of published studies. Proteomic research provides quantitative information on the course of viral infection, identifies sites and microheterogeneity of post-translational modifications, and reveals protein-protein interactions.
MOLECULAR & CELLULAR PROTEOMICS
(2021)