Article
Chemistry, Physical
Rylee Wander, Andrea M. Kaminski, Zhangjie Wang, Eduardo Stancanelli, Yongmei Xu, Vijayakanth Pagadala, Jine Li, Juno M. Krahn, Truong Quang Pham, Jian Liu, Lars C. Pedersen
Summary: The study presents the crystal structures of 3-OST-5 with substrates and PAP, revealing its substrate specificity and anti-factor Xa activity. The enzyme prefers to sulfate a 6-O-sulfo glucosamine saccharide that is surrounded by glucuronic acid. Additionally, it was found that substrate specificity is not only determined by the side chains of amino acid residues in the active site, but also by the conformational flexibility of 2-O-sulfated iduronic acid in the saccharide substrates.
Article
Allergy
Konrad Bork, Karin Wulff, Britta S. Moehl, Lars Steinmueller-Magin, Gunther Witzke, Jochen Hardt, Peter Meinke
Summary: The study identified a novel disease-linked mutation for HAEnCI using whole exome sequencing, which affects HS biosynthesis and likely disrupts cell surface interactions of key players in angioedema formation.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Clinical Neurology
Natalia Perez-Lopez, Carla Martin, Beatriz Garcia, Maria Pilar Solis-Hernandez, David Rodriguez, Ignacio Alcalde, Jesus Merayo, Ivan Fernandez-Vega, Luis M. Quiros
Summary: The saccharide chains of heparan sulfate play a crucial role in the pathogenesis of Alzheimer's disease, with differential transcription of biosynthetic genes observed in different brain regions and stages of AD pathology. The study revealed more alterations in gene transcription in moderate AD patients compared to mild cases, with fewer changes in genes related to early stages of synthesis in severe patients and an overexpression of late-stage genes. These alterations correlated with progressive brain atrophy, particularly in the cerebellum, and were consistent with immunohistochemical detection of certain heparan sulfate epitopes.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2021)
Article
Chemistry, Applied
Tianji Zhang, Mingjia Yu, Honglian Li, Marco Maccarana, Wei Zhang, Deling Shi, Ying Kan, Xiao Zhang, Lianli Chi, Ulf Lindahl, Hongmei Li, Jin-ping Li, Tianwei Tan
Summary: This study investigated the functional interactions between glucuronyl 5-epimerase (Hsepi) and hexuronyl 2-O-sulfotransferase (Hs2st) and glucosaminyl 6-O-sulfotransferase (Hs6st) using an isotope exchange approach. The results showed that the binding of these enzymes plays an important role in the efficiency of substrate conversion. Furthermore, experimental evidence suggested the formation of a functional complex between Hsepi and Hs6st in cells, and the inability to achieve simultaneous 2-O and 6-O sulfation in vitro.
CARBOHYDRATE POLYMERS
(2023)
Article
Endocrinology & Metabolism
Yizhou Huang, Lizhi Chen, Ziyi Tang, Yu Min, Wanli Yu, Gangyi Yang, Lili Zhang
Summary: By analyzing data from the TCGA database, the study identified ITK as a potential indicator for prognosis prediction in patients with breast cancer, and its expression was associated with immune activity in the tumor microenvironment.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
John R. Couchman
Summary: Cell surface proteoglycans, such as syndecans, play crucial roles in regulating cell behavior, including interactions with extracellular matrix components and mediating proliferation, adhesion, and migration. In tumors, changes in the levels and distribution of syndecan-1 can have implications for prognosis, with loss of membrane staining and abnormal cytoplasmic or nuclear staining often indicating poor outcomes. Targeting syndecan-1 with antibody-toxin conjugates may hold promise for clinical applications in both myeloma and some carcinomas.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
J. Michael Sorrell, Arnold Caplan
Summary: White adipose tissues are crucial endocrine organs that release adipokines, affecting other major organ systems. The development and functions of adipose tissues rely heavily on the glycosaminoglycan heparan sulfate, which regulates cellular physiology and communication. Understanding the role of heparan sulfates in the regulation of adipokine production and release could provide valuable insights into tissue engineering and experimental studies.
Review
Cell Biology
Jian Liu, Lars C. Pedersen
Summary: This article summarizes the recent progress in substrate specificity studies of different 3-O-sulfotransferase isoforms and introduces a newly developed method for analyzing the level of 3-O-sulfated heparan sulfate using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Oncology
Yan Yang, Xin He, Qian-Qian Tang, You-Cheng Shao, Wen-Jing Song, Peng-Ju Gong, Yi-Fan Zeng, Si-Rui Huang, Jiang-Yao Zhou, Hui-Fang Wan, Lei Wei, Jing-Wei Zhang
Summary: The research identified the immune gene GMFG as an important prognostic marker for breast cancer, with lower expression linked to poor prognosis. GMFG expression was also associated with tumor subtype, growth, and infiltration of CD8+ T cells, suggesting an anti-tumor role in breast cancer. GMFG has the potential to become a novel immune biomarker for the diagnosis and treatment of breast cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Julia Kuehn, Nancy Adriana Espinoza-Sanchez, Felipe C. O. B. Teixeira, Mauro S. G. Pavao, Ludwig Kiesel, Balazs Gyorffy, Burkhard Greve, Martin Goette
Summary: The hedgehog pathway plays an important role in the development and prognosis of breast cancer, with specific heparan sulfate sulfotransferases providing novel insights for therapeutic targeting. The GLI transcription factors are suggested as possible markers for diagnosis, treatment, and prognosis, especially in HER2-positive tumors.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Hao Cui, Zhaoguang Wang, Tianji Zhang, Jin-ping Li, Jianping Fang
Summary: The translation explores the role of Heparan sulfate (HS) in protein recognition and interaction, highlighting the importance of specific sulfation and epimerization patterns modulated by Golgi-localized enzymes. The study investigates the effects of restoring Hsepi in mutant MEF cells, showing increased IdoA residues and rescued cell signaling, although Hsepi knockout did not influence cellular transport or enzymatic activity of 2OST. These findings suggest potential differences in regulatory mechanisms for 2OST and Hsepi.
Article
Peripheral Vascular Disease
Olga Berillo, Sofiane Ouerd, Noureddine Idris-Khodja, Asia Rehman, Chantal Richer, Daniel Sinnett, Anne E. Kwitek, Pierre Paradis, Ernesto L. Schiffrin
Summary: Chromosome 2 introgression from normotensive Brown Norway rats reduced blood pressure and vascular inflammation in hypertensive Dahl salt-sensitive rats, with two differentially expressed genes identified: Enpep associated with reduced vascular inflammation under NSD, and Hs2st1 associated with increased vascular inflammation under HSD.
Article
Medicine, Research & Experimental
Stefan Lennard Krautschneider, Fabian M. Troschel, Eduardo Vadillo, Hans Theodor Eich, Martin Goette, Nancy Adriana Espinoza-Sanchez, Burkhard Greve
Summary: This study aimed to investigate the interplay between heparan sulfate (HS) degradation and radiation response in triple-negative breast cancer (TNBC) cells. The results showed significantly increased radioresistance and cell migration after HS degradation. Furthermore, the expression and activation of certain signaling pathway molecules were altered after HS degradation, impacting the radiation resistance of TNBC cells.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Article
Biochemical Research Methods
Chenming Guo, Zhiwen Luo, Dilimulati Ismtula, Xiaojuan Bi, Han Kong, Yiyang Wang, Zhen Yang, Xinmin Mao
Summary: This study assessed the levels and potential therapeutic and prognostic significance of TIGIT in invasive breast cancer. The results showed that TIGIT was elevated in invasive breast cancer and closely associated with prognosis. Further analyses revealed correlations between TIGIT levels and specific clinicopathological features as well as immune cell infiltrations.
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
(2023)
Article
Oncology
Claudia Alexandra Dumitru, Eileen Brouwer, Tamina Stelzer, Salvatore Nocerino, Sebastian Rading, Ludwig Wilkens, Ibrahim Erol Sandalcioglu, Meliha Karsak
Summary: The study identified Tctex1 as an independent prognostic marker for overall survival in GBM patients, with high expression significantly associated with short overall survival and progression-free survival. Tctex1 promotes the aggressiveness and proliferation of GBM cells, indicating its potential as a therapeutic target in GBM.
Article
Biochemistry & Molecular Biology
Guanglin Niu, Isabel Hellmuth, Tatiana Flisikowska, Hubert Pausch, Beate Rieblinger, Alexander Carrapeiro, Benjamin Schade, Brigitte Boehm, Eva Kappe, Konrad Fischer, Bernhard Klinger, Katja Steiger, Reiner Burgkart, Jean-Christophe Bourdon, Dieter Saur, Alexander Kind, Angelika Schnieke, Krzysztof Flisikowski
Summary: The mutation in TP53 gene in pig models leads to the development of tumors like osteosarcoma, pointing out similarities with human TP53. Specific TP53 isoforms determine the tumor spectrum in pigs, with circTP53 playing a critical role in malignant transformation.
Article
Oncology
Kevin Jan Legscha, Edite Antunes Ferreira, Antonios Chamoun, Alexander Lang, Mohamed Hemaid Sayed Awwad, Gigi Nu Hoang Quy Ton, Danuta Galetzka, Borhane Guezguez, Michael Hundemer, Jean-Christophe Bourdon, Markus Munder, Matthias Theobald, Hakim Echchannaoui
Summary: This study revealed a broad effect of the Delta 133p53 alpha isoform in regulating T lymphocyte function. Enhancing the fitness and effector functions of senescent T cells by modulating p53 isoforms could be utilized for future translational research to improve cancer immunotherapy and immunosenescence-related diseases.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Hematology
Elizabeta A. Rojas, Luis A. Corchete, Cristina De Ramon, Patryk Krzeminski, Dalia Quwaider, Ramon Garcia-Sanz, Joaquin Martinez-Lopez, Albert Oriol, Laura Rosinol, Joan Blade, Juan Jose Lahuerta, Jesus F. San Miguel, Marcos Gonzalez, Maria Victoria Mateos, Jean-Christophe Bourdon, Irena Misiewicz-Krzeminska, Norma C. Gutierrez
Summary: This study demonstrates for the first time the prognostic value of p53 isoforms in multiple myeloma patients, providing new insights into the role of p53 protein dysregulation in multiple myeloma biology.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Sunali Mehta, Hamish Campbell, Catherine J. Drummond, Kunyu Li, Kaisha Murray, Tania Slatter, Jean-Christophe Bourdon, Antony W. Braithwaite
Summary: p53 is a crucial protein in maintaining biological homeostasis, with its network playing a vital role in maintaining stability within multicellular organisms, facilitating cooperation between cells to adapt to environmental changes.
Article
Oncology
Xiajie Zhang, Kira Groen, Brianna C. Morten, Luiza Steffens Reinhardt, Hamish G. Campbell, Antony W. Braithwaite, Jean-Christophe Bourdon, Kelly A. Avery-Kiejda
Summary: This study aimed to evaluate the role of Delta 40p53 in breast cancer migration and invasion, finding an association between Delta 40p53 and gene expression profiles. Knockdown of both p53 alpha and Delta 40p53 resulted in increased proliferation, while overexpression of Delta 40p53 reduced proliferation rates and decreased migratory and invasive properties of the cells. These results suggest that at a basal level, Delta 40p53 works similarly to p53 alpha in suppressing cellular mobility and proliferation.
MOLECULAR ONCOLOGY
(2022)
Article
Cell Biology
Yitian Guo, Melanie Rall-Scharpf, Jean-Christophe Bourdon, Lisa Wiesmuller, Stephanie Biber
Summary: This study demonstrates that different p53 isoforms have varying effects on the p53-POL iota-dependent DNA damage tolerance (DDT) pathway. Despite lacking the biochemical activities required for this pathway, all alternative isoforms exhibit impairments in promoting POL iota recruitment to PCNA and decelerating DNA replication.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Sajida Khan, Malak Sbeity, Francois Foulquier, Lydia Barre, Mohamed Ouzzine
Summary: TMEM165 deficiency leads to skeletal disorder characterized by skeletal dysplasia and dwarfism. The study found that TMEM165 deficiency impairs the synthesis of proteoglycans, resulting in shorter glycosaminoglycan chains. Additionally, TMEM165 deficiency affects TGF beta and BMP signaling pathways in chondrocytes and accelerates chondrogenic differentiation.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Flora Nguyen Van Long, Audrey Lardy-Cleaud, Dimitri Carene, Caroline Rossoni, Frederic Catez, Paul Rollet, Nathalie Pion, Deborah Monchiet, Agathe Dolbeau, Marjorie Martin, Valentin Simioni, Susan Bray, Doris Le Beherec, Fernanda Mosele, Ibrahim Bouakka, Amelie Colombe-Vermorel, Laetitia Odeyer, Alexandra Diot, Lee B. Jordan, Alastair M. Thompson, Francoise Jamen, Thierry Dubois, Sylvie Chabaud, Stefan Michiels, Isabelle Treilleux, Jean-Christophe Bourdon, David Perol, Alain Puisieux, Fabrice Andre, Jean-Jacques Diaz, Virginie Marcel
Summary: FBL has been identified as a powerful independent marker of breast cancer prognosis related to ribosome biogenesis. Surprisingly, low activation of ribosome biogenesis is also associated with poor outcome.
Article
Cell Biology
Zoe Durin, Marine Houdou, Willy Morelle, Lydia Barre, Aurore Layotte, Dominique Legrand, Mohamed Ouzzine, Francois Foulquier
Summary: Glycosylation is a universal cellular process that can lead to severe genetic diseases. Oral D-Galactose therapy shows promise in treating specific CDG, while MnCl2 supplementation can fully rescue glycosylation defects caused by TMEM165 deficiency. However, D-Galactose only affects N-linked glycosylation while MnCl2 supplementation rescues all glycosylation types.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Luiza Steffens Reinhardt, Kira Groen, Brianna C. Morten, Jean-Christophe Bourdon, Kelly A. Avery-Kiejda
Summary: TP53 mutations are associated with tumor progression, therapy resistance, and poor prognosis in breast cancer. However, other mechanisms, such as p53 isoform dysregulation, may contribute to the disruption of the p53 pathway. This study found that high levels of p53 beta, a N-terminally truncated variant, were significantly associated with worse disease-free survival, especially in tumors with wild-type TP53, suggesting that p53 beta may serve as a prognostic marker in breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Muyang Li, Fredrick Philantrope, Alexandra Diot, Jean-Christophe Bourdon, Patricia Thompson
Summary: In this study, we found that inhibition of SMG1 in MCF7 tumor cells induces increased expression of p53 beta and p53 gamma, as well as upregulation of several cholesterol pathway genes. Our study also revealed that silencing SMG1 leads to increased expression of ABCA1, a cholesterol efflux pump, and this may be related to the differential effects of p53 isoforms on cholesterol gene expression.
Article
Cell Biology
Luiza Steffens Reinhardt, Xiajie Zhang, Kira Groen, Brianna C. Morten, Geoffry N. De Iuliis, Antony W. Braithwaite, Jean-Christophe Bourdon, Kelly A. Avery-Kiejda
Summary: This study found that the response of breast cancer cells to DNA-damaging therapies in standard care is dependent on the expression of p53 isoforms. A high Delta 40p53:p53 alpha ratio causes cells to respond differently to doxorubicin and cisplatin treatments, increasing resistance to doxorubicin and promoting DNA repair, thereby impairing the cells' normal response.
CELL DEATH & DISEASE
(2022)
Article
Pharmacology & Pharmacy
Michael J. J. Doerksen, Denny Seo, Alexander D. D. Smith, Robert S. S. Jones, Michael W. H. Coughtrie, Abby C. C. Collier
Summary: In this study, hepatic GST conjugation was investigated in mouse and rat strains compared to humans. The results showed that all mouse strains had higher activities of total cytosolic GST, GST-M, GST-T, and microsomal GST compared to humans, with some strains also having higher GST-P activities. Sex differences were observed in all strains for several GST activities. Similarly, rats exhibited higher activities of GST-M and GST-T compared to humans, with some strains also showing higher activities of GST-P, total cytosolic GST, and microsomal GST. Sex differences were also observed in some strains for certain GST activities. These findings highlight the importance of careful selection of animal models in pre-clinical studies where GSTs are involved in drug metabolism.
Article
Cell Biology
Mahdia Taieb, Dima Ghannoum, Lydia Barre, Mohamed Ouzzine
Summary: Genetic mutations in the Xylt1 gene are associated with Desbuquois dysplasia type II syndrome characterized by sever prenatal and postnatal short stature. The study reveals the specific role of XylT-I in the growth plate and its importance in the synthesis of proteoglycans.
CELL DEATH & DISEASE
(2023)
Correction
Biochemistry & Molecular Biology
Virginie Marcel, Janice Kielbassa, Virginie Marchand, Kundhavai S. Natchiar, Hermes Paraqindes, Flora Nguyen Van Long, Lilia Ayadi, Valerie Bourguignon-Igel, Piero Lo Monaco, Deborah Monchiet, Veronique Scott, Laurie Tonon, Susan E. Bray, Alexandra Diot, Lee B. Jordan, Alastair M. Thompson, Jean-Christophe Bourdon, Thierry Dubois, Fabrice Andre, Frederic Catez, Alain Puisieux, Yuri Motorin, Bruno P. Klaholz, Alain Viari, Jean-Jacques Diaz