Review
Biochemistry & Molecular Biology
Cyril Balsollier, Roland J. Pieters, Marko Anderluh
Summary: O-GlcNAcylation is a critical posttranslational modification process that has sparked interest in the medical community. While OGA inhibitors are in clinical trials, finding potent OGT inhibitors remains challenging due to complex expression and instability.
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)
Article
Cell Biology
Lorela Ciraku, Emily M. Esquea, Mauricio J. Reginato
Summary: O-GlcNAcylation is a post-translational modification affecting protein stability, interactions, and phosphorylation, playing a crucial role in nutrient sensing and regulation of cancer signaling pathways. Its elevated levels have been linked to various cancers, making it a potential target for cancer treatment.
CELLULAR SIGNALLING
(2022)
Article
Biochemistry & Molecular Biology
Yang Li, Zelan Yang, Jia Chen, Yihao Chen, Chengji Jiang, Tao Zhong, Yanting Su, Yi Liang, Hui Sun
Summary: This study successfully established an OGT binding peptide (OBP)-tagged strategy to improve the proportion of O-GlcNAc modification. By fusing OBP with the target protein Tau and co-constructing with OGT in E. coli, the O-GlcNAc level of P1Tau and TauP1 increased 4 to 6-fold compared to Tau alone. This strategy was also applied successfully to increase the O-GlcNAc level of c-Myc and H2B.
Article
Oncology
An-Ping Lin, Zhijun Qiu, Purushoth Ethiraj, Binu Sasi, Carine Jaafar, Dinesh Rakheja, Ricardo C. T. Aguiar
Summary: Mitochondria can act as signaling organelles and play a role in epigenetic remodeling. MYC transcriptionally activates IDH2, leading to increased levels of alpha-ketoglutarate (alpha KG). This activation induces the activity of alpha KG-dependent DNA hydroxylases and RNA demethylases, resulting in decreased global DNA and RNA methylation. Additionally, MYC promotes the nuclear accumulation of certain enzymes involved in DNA and RNA demethylation through an IDH2-dependent mechanism. Interestingly, this subcellular movement is correlated with the ability of MYC and alpha KG to induce O-GlcNAcylation, which can influence the epigenome and epitranscriptome homeostasis.
Article
Multidisciplinary Sciences
Zebulon G. Levine, Sarah C. Potter, Cassandra M. Joiner, George Q. Fei, Behnam Nabet, Matthew Sonnett, Natasha E. Zachara, Nathanael S. Gray, Joao A. Paulo, Suzanne Walker
Summary: O-GlcNAc transferase (OGT) is crucial for cell proliferation, with its glycosyl-transferase function essential for cell growth while its protease function is dispensable. OGT also plays an essential noncatalytic role in cell proliferation, with its noncatalytic functions affecting different proteins from its catalytic functions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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
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)
Article
Biology
Mackenzie Moore, Nandini Avula, Alicia Wong, Megan Beetch, Seokwon Jo, Emilyn U. Alejandro
Summary: This study suggests that reducing pancreatic OGT levels can alleviate the severity of pancreatitis, pointing to the need for further investigation on the role of OGT in the pathology of AP.
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)
Article
Biochemistry & Molecular Biology
Philip Ryan, Yun Shi, Mark von Itzstein, Santosh Rudrawar
Summary: This study reports novel uridine-peptide conjugate molecules with inhibitory activities against O-GlcNAc transferase (OGT) and evaluates their potency through a radioactive hOGT assay. Molecular modeling is used to investigate the structural basis of their activities, explaining their lack of potency towards OGT inhibition.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Giulia Bandini, Carolina Agop-Nersesian, Hanke van der Wel, Msano Mandalasi, Hyun W. Kim, Christopher M. West, John Samuelson
Summary: The study shows that TgSPY functions as a nucleocytoplasmic O-fucosyltransferase in Toxoplasma gondii, with the ability to modify proteins and hydrolyze GDP-Fuc. While O-fucosylation is important for tachyzoite fitness, the absence of TgSPY is not essential. Therefore, TgSPY likely controls protein levels to respond to new stresses.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Lianghao Zhai, Xiaoshan Yang, Jian Dong, Luomeng Qian, Yunge Gao, Yanhong Lv, Ligang Chen, Biliang Chen, Fuxing Zhou
Summary: The incidence of endometrial cancer (EC) is increasing globally. The study aimed to investigate the effects of O-GlcNAcylation on EC malignancy and its association with YAP. It was found that O-GlcNAc transferase (OGT) and O-GlcNAcylation were increased in EC tissues, and reducing O-GlcNAcylation levels decreased the proliferation, migration, and invasion of EC cells. Knockdown of OGT reduced the O-GlcNAcylation of YAP, which promoted its phosphorylation, inhibited YAP's nuclear access and downstream target gene activation, demonstrating that the level of O-GlcNAcylation affects EC development.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Review
Endocrinology & Metabolism
Jie Ning, Huixia Yang
Summary: This article focuses on the impact of O-GlcNAcylation on placental functions in hyperglycemia-associated pregnancies, including its effects on placental development, maternal-fetal nutrition transport, and inflammation regulation.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Oncology
Chia-Hung Lin, Chen-Chung Liao, Shu-Ying Wang, Chia-Yi Peng, Yi-Chen Yeh, Mei-Yu Chen, Teh-Ying Chou
Summary: Lung cancer is the most deadly type of cancer, and invasion and metastasis are major challenges in its treatment. O-GlcNAcylation, a protein modification process, is linked to cancer pathogenesis, including invasion and metastasis. However, little is known about O-GlcNAcylated proteins involved in cancer aggressiveness. In this study, we compared the profiles of O-GlcNAcylated proteins in two lung cancer cell lines with different invasive potentials and identified potential candidates involved in cancer aggressiveness. Further characterization of one candidate, SAM68, confirmed its O-GlcNAcylation and suggested its role in regulating lung cancer cell migration and invasion. Our findings provide new insights into the mechanisms of lung cancer progression through O-GlcNAcylated proteins.
Article
Endocrinology & Metabolism
Louis Masclef, Vanessa Dehennaut, Marlene Mortuaire, Celine Schulz, Maite Leturcq, Tony Lefebvre, Anne-Sophie Vercoutter-Edouart
FRONTIERS IN ENDOCRINOLOGY
(2019)
Article
Endocrinology & Metabolism
Elia Torres-Gutierrez, Yobana Perez-Cervera, Luc Camoin, Edgar Zenteno, Moyira Osny Aquino-Gil, Tony Lefebvre, Margarita Cabrera-Bravo, Olivia Reynoso-Ducoing, Martha Irene Bucio-Torres, Paz Maria Salazar-Schettino
FRONTIERS IN ENDOCRINOLOGY
(2019)
Article
Endocrinology & Metabolism
Gabriela Fuentes-Garcia, M. Cristina Castaneda-Patlan, Anne-Sophie Vercoutter-Edouart, Tony Lefebvre, Martha Robles-Flores
FRONTIERS IN ENDOCRINOLOGY
(2019)
Article
Biochemical Research Methods
James Biwi, Charlotte Clarisse, Christophe Biot, Radoslaw Pawel Kozak, Katarina Madunic, Marlene Mortuaire, Manfred Wuhrer, Daniel Ian Richard Spencer, Celine Schulz, Yann Guerardel, Tony Lefebvre, Anne-Sophie Vercoutter-Edouart
Article
Biochemistry & Molecular Biology
Amelie Decourcelle, Ingrid Loison, Steffi Baldini, Dominique Leprince, Vanessa Dehennaut
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Jose Benito Lopez-Salguero, Reyna Fierro, Jean-Claude Michalski, Irma Jimenez-Morales, Tony Lefebvre, Oscar Mondragon-Payne, Steffi F. Baldini, Anne-Sophie Vercoutter-Edouart, Humberto Gonzalez-Marquez
GLYCOCONJUGATE JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Angelina Kasprowicz, Corentin Spriet, Christine Terryn, Vincent Rigolot, Stephan Hardiville, Matthew G. Alteen, Tony Lefebvre, Christophe Biot
Article
Biochemistry & Molecular Biology
Sonia Paget, Marion Dubuissez, Adeline Page, Vanessa Dehennaut, Ingrid Loison, Nathalie Spruyt, Dominique Leprince
Summary: HIC1 is a tumor suppressor gene encoding a transcriptional repressor that plays a role in the DNA-damage response. Specific posttranslational modifications, such as phosphorylation and acetylation, are crucial for the function of HIC1 and its activity in DNA repair. These modifications are essential for HIC1-mediated cellular response to repairable DNA double strand breaks.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sadia Raab, Alexis Gadault, Ninon Very, Amelie Decourcelle, Steffi Baldini, Celine Schulz, Marlene Mortuaire, Quentin Lemaire, Stephan Hardiville, Vanessa Dehennaut, Ikram El Yazidi-Belkoura, Anne-Sophie Vercoutter-Edouart, Ganna Panasyuk, Tony Lefebvre
Summary: Research has shown that fatty acid synthase (FASN) interacts with O-GlcNAc transferase (OGT) in the cell, and is involved with the PI3K/AKT/mTOR signaling pathway to regulate cell cycle and tumorigenesis in hepatic cells. This indicates a novel reciprocal regulation between FASN, OGT, and mTOR signaling in the promotion of hepatic tumors.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Oncology
Pawel Jozwiak, Piotr Ciesielski, Piotr K. Zakrzewski, Karolina Kozal, Joanna Oracz, Grazyna Budryn, Dorota Zyzelewicz, Stephanie Flament, Anne-Sophie Vercoutter-Edouart, Fabrice Bray, Tony Lefebvre, Anna Krzeslak
Summary: Our study investigated the impact of mitochondrial OGT on O-GlcNAcylation of mitochondrial proteins, mitochondrial function, and energy metabolism in breast cancer cells. We found evidence suggesting that mOGT interacts with and modifies multiple mitochondrial proteins, potentially affecting cellular bioenergetics and mitochondria function.
Article
Biochemistry & Molecular Biology
Ninon Very, Stephan Hardiville, Amelie Decourcelle, Julien Thevenet, Madjid Djouina, Adeline Page, Gerard Vergoten, Celine Schulz, Julie Kerr-Conte, Tony Lefebvre, Vanessa Dehennaut, Ikram El Yazidi-Belkoura
Summary: Alteration of O-GlcNAcylation affects tumorigenesis and tumor progression, with a potential role in chemotherapy response. Combination treatment of 5-FU with Thiamet-G shows synergistic inhibitory effects on CRC progression by regulating TS and O-GlcNacylation levels. Overall, the findings suggest a new approach to enhance CRC response to 5-FU chemotherapy by targeting O-GlcNAcylation.
Review
Cell Biology
Awatef Ben Ahmed, Quentin Lemaire, Jodie Scache, Christophe Mariller, Tony Lefebvre, Anne-Sophie Vercoutter-Edouart
Summary: The transport of proteins in cells is regulated by the secretory pathway, as well as unconventional secretion pathways. These complex processes rely on various signaling and regulatory proteins to ensure proper delivery of cargoes. O-GlcNAcylation, a reversible post-translational modification, plays a role in protein trafficking in mammalian cells through classical and unconventional secretory pathways. This review summarizes the emerging role of O-GlcNAc modification in protein trafficking.
Article
Oncology
Amelie Decourcelle, Ninon Very, Madjid Djouina, Ingrid Loison, Julien Thevenet, Mathilde Body-Malapel, Eric Lelievre, Olivier Coqueret, Dominique Leprince, Ikram El Yazidi-Belkoura, Vanessa Dehennaut