Review
Biochemistry & Molecular Biology
Iason Psilopatis, Eleni Souferi-Chronopoulou, Kleio Vrettou, Constantinos Troungos, Stamatios Theocharis
Summary: EPHs/ephrins appear to be promising treatment targets in the future for breast cancer, with EPHA2 being the most studied target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Iason Psilopatis, Ioannis Karniadakis, Konstantinos Stylianos Danos, Kleio Vrettou, Kleita Michaelidou, Konstantinos Mavridis, Sofia Agelaki, Stamatios Theocharis
Summary: Lung cancer is the leading cause of cancer death in the United States. Erythropoietin-producing hepatocellular receptors (EPHs) and their ligands ephrins play a defining role in the development and progression of lung cancer. Targeting EPHs/ephrins may provide effective treatment options for precision cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Reproductive Biology
Enoch Appiah Adu-Gyamfi, Armin Czika, Tai-Hang Liu, Philip Narteh Gorleku, Linda Ahenkorah Fondjo, Francis Tanam Djankpa, Yu-Bin Ding, Ying-Xiong Wang
Summary: Ephrins and Eph receptors play important roles in the female reproductive system, regulating various processes and being associated with obstetric and gynecologic disorders.
BIOLOGY OF REPRODUCTION
(2021)
Article
Chemistry, Medicinal
Maricel Gomez-Soler, Erika J. Olson, Elena Rubio de la Torre, Chunxia Zhao, Ilaria Lamberto, Dillon T. Flood, Waleed Danho, Bernhard C. Lechtenberg, Stefan J. Riedl, Elena B. Pasquale, Philip E. Dawson
Summary: The EphA4 receptor tyrosine kinase is involved in several diseases and inhibiting its activity could have therapeutic potential. Researchers have identified a peptide antagonist that specifically inhibits the binding of ephrin ligands to EphA4. They have also modified the peptide to improve its stability and activity. These derivatives could be useful for studying EphA4 in vivo and for testing EphA4 inhibition in animal models.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Junhao Lin, Chunting Zeng, JiaKang Zhang, Zhenghui Song, Na Qi, Xinhui Liu, Ziyan Zhang, Aimin Li, Fengsheng Chen
Summary: EFNA4 plays a crucial role in promoting proliferation and migration of HCC cells, and its overexpression is associated with poor prognosis. EFNA4 regulates the PIK3R2/GSK3 beta/beta-catenin loop to influence the survival and migration of HCC cells.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Review
Biochemistry & Molecular Biology
Radoslaw Kaczmarek, Katarzyna Zimmer, Pawel Gajdzis, Malgorzata Gajdzis
Summary: The cornea, though simple in appearance, is a highly complex structure that requires perfect organization of cells for maintaining its biomechanical and optical properties. Eph receptors and ephrins play a crucial role in tissue organization, cell migration, and communication, particularly in the regeneration process following injuries and diseases. This review examines the current understanding of Eph and ephrins in corneal physiology and diseases, with a focus on the epithelium and endothelium, as well as their influence on corneal neovascularization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
David G. Wilkinson
Summary: Cell segregation to form sharp boundaries is crucial for stabilizing tissue organization and is driven by differential adhesion mediated by cadherins and Eph receptor/ephrin signaling regulating cell adhesion, cortical tension, and repulsion. These mechanisms interplay with cadherins antagonizing homotypic tension within cell populations and Eph receptors mainly driving segregation through increased heterotypic tension or repulsion. The differential tension between homotypic and heterotypic tensions ultimately leads to cell segregation and border sharpening.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sho Kohara, Kazushige Ogawa
Summary: Kupffer cells are maintained through self-renewal within liver sinusoidal endothelial cells (LSECs). In this study, liver macrophages (Mo) were propagated from mice using mixed culture with hepatic fibroblastic cells. The propagated liver Mo expressed specific transcription factors and exhibited similar gene expression and surface markers as primary LSECs, suggesting that their properties resemble those of Kupffer cells. Further investigation revealed the expression of certain Eph receptors and ephrin ligands, as well as integrin subunits and corresponding ligands, potentially contributing to the adhesion and residence of Kupffer cells within the liver sinusoid.
Review
Pharmacology & Pharmacy
Massimiliano Tognolini, Alessio Lodola, Carmine Giorgio
Summary: The recent advancement in computer power and AI algorithms has led to inexperienced scientists attempting to use computer aided drug design to discover new drugs, potentially overshadowing the importance of wet lab data and neglecting the synergy between in silico and biological data in successful drug discovery.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Cell Biology
Lujuan Wang, Wei Li, Yong Pan
Summary: The Eph/Ephrins system plays a dual role in both suppressing and promoting tumors in primary bone tumors and bone cancer pain. Understanding the intracellular mechanisms of the Eph/Ephrins system in tumorigenesis and metastasis of bone tumors may provide a foundation for the development of targeted anti-cancer therapy.
Article
Cell Biology
Michael P. Vu, Catherine Cheng
Summary: The eye lens plays a crucial role in focusing light onto the retina, while cataracts are a major cause of blindness worldwide. Recent studies have shown the importance of Eph-ephrin bidirectional signaling in maintaining lens transparency. This study investigated the expression of Eph receptors and ephrin ligands in different cell fractions of the lens, revealing the presence of multiple receptor-ligand pairs that may contribute to lens homeostasis.
Article
Gastroenterology & Hepatology
Abdullah Husain, Yung-tuen Chiu, Karen Man-Fong Sze, Daniel Wai-Hung Ho, Yu-Man Tsui, Eliana Marry Senires Suarez, Vanilla Xin Zhang, Lo-Kong Chan, Eva Lee, Joyce Man-Fong Lee, Tan-To Cheung, Carmen Chak-Lui Wong, Clive Yik-Sham Chung, Irene Oi-Lin Ng
Summary: In hepatocellular carcinoma (HCC), the Ephrin-A3/EphA2 axis plays a significant role as a hypoxia-sensitive modulator of HCC cell metabolism and a key contributor to HCC initiation and progression.
JOURNAL OF HEPATOLOGY
(2022)
Article
Pharmacology & Pharmacy
Peishan Qiu, Daojiang Li, Cong Xiao, Fei Xu, Xiaoyu Chen, Ying Chang, Lan Liu, Lei Zhang, Qiu Zhao, Yuhua Chen
Summary: The extent of gut inflammation depends on the gut barrier's integrity and enteric neuroimmune interactions. The role of Eph/ephrin signaling in regulating gut homeostasis, inflammation, neuroimmune interactions, and pain pathways is critical. Targeting the Eph/ephrin system provides innovative treatments for gut inflammation disorders.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Alessandra Cecchini, D. D. W. Cornelison
Summary: Intracellular signal transduction is a linear process involving interactions between membrane-associated proteins. The Eph/ephrin family is a group of molecules that regulate cell activities through lateral interactions at the cell surface. The response to Eph/ephrin interaction varies greatly between cell types and is dependent on the cellular context.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Oncology
Stavros P. Papadakos, Ioanna E. Stergiou, Nikolina Gkolemi, Konstantinos Arvanitakis, Stamatios Theocharis
Summary: This narrative literature review focuses on the role of EPH/ephrin signaling in liver cancer and its implications for tumor progression and potential therapeutic strategies. It highlights the upregulation of HIF-1α in HCC cells under low oxygen conditions and explores the significance of the EPH/ephrin axis in regulating the hypoxic tumor microenvironment. The review also emphasizes the potential of targeting the EPH/ephrin signaling pathway in liver cancer treatment.
Article
Biochemistry & Molecular Biology
Ariel Erijman, Lukasz Kozlowski, Salma Sohrabi-Jahromi, James Fishburn, Linda Warfield, Jacob Schreiber, William S. Noble, Johannes Soeding, Steven Hahn
Article
Microbiology
Eli Levy Karin, Milot Mirdita, Johannes Soeding
Article
Biochemical Research Methods
Ruoshi Zhang, Milot Mirdita, Eli Levy Karin, Clovis Norroy, Clovis Galiez, Johannes Soeding
Summary: SpacePHARER is a sensitive and fast tool for predicting phage-host relationships by comparing spacers and phages at the protein level, optimizing scores for matching short sequences, and combining evidence from multiple matches.
Article
Biochemical Research Methods
M. Mirdita, M. Steinegger, F. Breitwieser, J. Soeding, E. Levy Karin
Summary: MMseqs2 taxonomy is a new tool for assigning taxonomic labels to metagenomic contigs. It extracts protein fragments from each contig, retains those relevant for taxonomic annotation, and determines the taxonomic identity using weighted voting. MMseqs2 is 2-18 times faster than existing tools and includes modules for creating and manipulating taxonomic reference databases.
Article
Biology
Jinmi Choi, Kseniia Lysakovskaia, Gregoire Stik, Carina Demel, Johannes Soeding, Tian Tian, Thomas Graf, Patrick Cramer
Summary: Enhancer activity plays a crucial role in cell differentiation and cell fate determination. This study demonstrates that while most putative enhancers cooperate in an additive manner, some enhancers synergistically regulate the transcription of target genes, which are cell type-specific and can contribute to cell fate determination. Enhancer synergy appears to depend on cell type-specific transcription factors and cannot be predicted from occupancy or accessibility data used to detect superenhancers.
Article
Biochemical Research Methods
Salma Sohrabi-Jahromi, Johannes Soeding
Summary: The study reveals that many RNA-binding proteins use bivalent binding to achieve higher affinity and sequence specificity. Furthermore, the spatial geometry between binding sites can be learned from bound RNA sequences to discover bipartite motifs, highlighting the importance of multivalent binding for protein-RNA interactions.
Article
Biochemistry & Molecular Biology
Zhan Qi, Christophe Jung, Peter Bandilla, Claudia Ludwig, Mark Heron, Anja Sophie Kiesel, Mariam Museridze, Julia Philippou-Massier, Miroslav Nikolov, Alessio Renna Max Schnepf, Ulrich Unnerstall, Stefano Ceolin, Bettina Muhlig, Nicolas Gompel, Johannes Soeding, Ulrike Gaul
Summary: Through a comprehensive structure-function analysis, it was found that the activity of the core promoter is influenced by different types of mutations, including knockout of individual sequence motifs and motif combinations, variations of motif strength, nucleosome positioning, and flanking sequences. A linear combination of the individual motif features largely explains the combinatorial effects on core promoter activity.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Anna Luebben, Daniel Bender, Stefan Becker, Lisa M. Crowther, Ilka Erven, Kay Hofmann, Johannes Soeding, Henry Klemp, Cristina Bellotti, Andreas Stauble, Tian Qiu, Rahul S. Kathayat, Bryan C. Dickinson, Jutta Gaertner, George M. Sheldrick, Ralph Kraetzner, Robert Steinfeld
Summary: Cln5, PPPDE1, and PPPDE2 have efficient cysteine palmitoyl thioesterase activity, but no protease activity. Mutational analysis reveals the key residues for Cln5 thioesterase activity. Cln5 regulates S-depalmitoylation levels in neurons, and this study uncovers a new enzymatic function for the N1pC/P60 superfamily of proteins.
Article
Biotechnology & Applied Microbiology
Michel van Kempen, Stephanie S. Kim, Charlotte Tumescheit, Milot Mirdita, Jeongjae Lee, Cameron L. M. Gilchrist, Johannes Soeding, Martin Steinegger
Summary: Foldseek aligns the structure of a query protein against a database by representing the tertiary amino acid interactions as sequences over a structural alphabet. It improves computation time by four to five orders of magnitude, with sensitivities of 86%, 88%, and 133% compared to Dali, TM-align, and CE, respectively. Foldseek significantly speeds up protein structural search.
NATURE BIOTECHNOLOGY
(2023)
Article
Genetics & Heredity
Simon H. Stitzinger, Salma Sohrabi-Jahromi, Johannes Soeding
Summary: Most RNA-binding domains have lower specificity and affinity compared to DNA-binding domains. However, cooperative binding of multiple domains in RNA-binding proteins can significantly enhance their affinity and specificity. A thermodynamic model is presented to calculate the effective binding affinity of sequence-specific RBPs with any number of RBDs. The model predictions align well with measurements for seven proteins with known domain affinities. Furthermore, the model explains how a two-fold increase in binding site density on RNA can lead to a ten-fold increase in protein occupancy. Hence, it is proposed that local clusters of binding motifs serve as the physiological binding targets for multi-domain RBPs.
NAR GENOMICS AND BIOINFORMATICS
(2023)
Meeting Abstract
Biochemical Research Methods
Milot Mirdita, Hyunjoo Ji, Eli Levy Karin, Hans-Georg Sommer, Clovis Galiez, Johannes Soeding, Martin Steinegger
BMC BIOINFORMATICS
(2021)
Article
Genetics & Heredity
Wanwan Ge, Markus Meier, Christian Roth, Johannes Soeding
Summary: Predicting transcription factor binding affinities accurately is crucial for understanding transcriptional regulation, with models that can learn dependencies between positions showing improved predictions. However, these models are also more prone to overfitting and learning patterns merely correlated with TF binding.
NAR GENOMICS AND BIOINFORMATICS
(2021)
Review
Microbiology
Arnthor Aevarsson, Anna-Karina Kaczorowska, Bjorn Thor Adalsteinsson, Josefin Ahlqvist, Salam Al-Karadaghi, Joseph Altenbuchner, Hasan Arsin, Ulfur August Atlasson, David Brandt, Magdalena Cichowicz-Cieslak, Katy A. S. Cornish, Jeremy Courtin, Slawomir Dabrowski, Hakon Dahle, Samia Djeffane, Sebastian Dorawa, Julia Dusaucy, Francois Enault, Anita-Elin Fedoy, Stefanie Freitag-Pohl, Olafur H. Fridjonsson, Clovis Galiez, Eirin Glomsaker, Mickael Guerin, Sigurd E. Gundeso, Elisabet E. Gudmundsdottir, Hordur Gudmundsson, Maria Hakansson, Christian Henke, Alexandra Helleux, Jorn Remi Henriksen, Sigridur Hjorleifdottir, Gudmundur O. Hreggvidsson, Andrius Jasilionis, Annika Jochheim, Ilmur Jonsdottir, Lilja Bjork Jonsdottir, Agata Jurczak-Kurek, Tadeusz Kaczorowski, Jorn Kalinowski, Lukasz P. Kozlowski, Mart Krupovic, Karolina Kwiatkowska-Semrau, Olav Lanes, Joanna Lange, Julien Lebrat, Javier Linares-Pasten, Ying Liu, Steffen A. Lorentsen, Tobias Lutterman, Thibaud Mas, William Merre, Milot Mirdita, Agnieszka Morzywolek, Eric Olo Ndela, Eva Nordberg Karlsson, Edda Olgudottir, Cathrine Pedersen, Francine Perler, Solveig K. Petursdottir, Magdalena Plotka, Ehmke Pohl, David Prangishvili, Jessica L. Ray, Birkir Reynisson, Tara Robertsdottir, Ruth-Anne Sandaa, Alexander Sczyrba, Sigurlaug Skirnisdottir, Johannes Soding, Terese Solstad, Ida H. Steen, Sigmar Karl Stefansson, Martin Steinegger, Katrine Stange Overa, Bernd Striberny, Anders Svensson, Monika Szadkowska, Emma J. Tarrant, Paul Terzian, Mathilde Tourigny, Tom van den Bergh, Justine Vanhalst, Jonathan Vincent, Bas Vroling, Bjorn Walse, Lei Wang, Hildegard Watzlawick, Martin Welin, Olesia Werbowy, Ewa Wons, Ruoshi Zhang
Summary: The Virus-X project aims to explore the genetic diversity of viruses in extreme natural environments and develop new gene products with high innovation value for various applications. The consortium, consisting of experts from multiple European countries, has successfully utilized high throughput bioinformatics technologies to analyze viral metagenomes and develop a biodiscovery pipeline. Through collaboration and advanced technologies, the project has made significant contributions to various fields such as biotechnology and pharmaceuticals.
FEMS MICROBIOLOGY LETTERS
(2021)
Article
Biotechnology & Applied Microbiology
Saikat Banerjee, Franco L. Simonetti, Kira E. Detrois, Anubhav Kaphle, Raktim Mitra, Rahul Nagial, Johannes Soeding
Summary: Trans-acting expression quantitative trait loci (trans-eQTLs) play a significant role in expression heritability and can help uncover mechanisms underlying complex diseases. Tejaas predicts unique trans-eQTLs using a special method, showing enrichment in chromatin, enhancers, and other regulatory regions. They also overlap with disease-associated SNPs, indicating tissue-specific transcriptional regulation mechanisms.
Article
Biochemistry & Molecular Biology
Bi Zhao, Akila Katuwawala, Christopher J. Oldfield, A. Keith Dunker, Eshel Faraggi, Jorg Gsponer, Andrzej Kloczkowski, Nawar Malhis, Milot Mirdita, Zoran Obradovic, Johannes Soding, Martin Steinegger, Yaoqi Zhou, Lukasz Kurgan
Summary: DescribePROT is a database of predicted amino acid-level descriptors of protein structure and function, offering a comprehensive collection of descriptors predicted using accurate algorithms for key model organisms. Users can search and download pre-computed results for various research purposes. Future releases will expand the coverage of DescribePROT.
NUCLEIC ACIDS RESEARCH
(2021)
