Review
Biochemistry & Molecular Biology
Markus M. Kramer, Levin Lataster, Wilfried Weber, Gerald Radziwill
Summary: Biological signals are transduced and processed through a complex intracellular signaling network, leading to cell-specific responses. Optogenetic tools, based on genetically encoded light-sensing proteins, provide precise spatiotemporal control of signal transduction pathways in the absence of natural ligands, connecting light-regulated protein-protein interactions with the steering of signaling proteins. The engineering and application of optogenetic tools for the control of transmembrane receptors and their effector proteins allow for spatial and temporal control of signaling events.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Emily R. Ruskowitz, Brizzia G. Munoz-Robles, Alder C. Strange, Carson H. Butcher, Sebastian Kurniawan, Jeremy R. Filteau, Cole A. DeForest
Summary: Proteins play a crucial role in regulating various biological processes, and new techniques are needed to effectively control protein activity in living systems and biomaterials to study cell signaling and guide biological fate. This study presents a generalizable strategy for activating protein function with precise spatiotemporal control. By using a genetically encoded and light-activated SpyLigation (LASL), bioactive proteins can be reassembled from non-functional fragments with the help of cytocompatible light. The researchers demonstrate protein activation and subcellular localization control in solution, biomaterials, and living mammalian cells. These photoclick-based optogenetic approaches are expected to greatly contribute to understanding and directing complex cellular fates in both time and three-dimensional space.
Article
Biochemistry & Molecular Biology
Rita Borzsei, Bayartsetseg Bayarsaikhan, Balazs Zoltan Zsido, Beata Lontay, Csaba Hetenyi
Summary: PRMT5 is an important enzyme responsible for arginine methylation on various proteins. This study reveals that the phosphorylation of PRMT5 on T80 residue increases its methyltransferase activity and elevated levels of the enzyme were measured in certain types of cancer. The atomic level complex structure provides insights for the design of new inhibitors and further understanding of PRMT enzymes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Xiaofeng Zhang, Yue Chen, Sung Yun Jung, Xianju Li, Fanjie Meng, Bowen Zhong, Jun Qin, Yi Wang
Summary: In this study, the dynamic interaction network of EGFR wildtype and mutant NSCLC cell lines was characterized. It was found that while the core signaling modules and downstream pathways were maintained in the mutant cell line, receptor internalization and intracellular trafficking were delayed. Additionally, mutant EGFR-associated proteins that could affect EGFR functions in lung adenocarcinoma were identified.
JOURNAL OF PROTEOMICS
(2022)
Review
Plant Sciences
Jincheng Li, Manqi Zhang, Lijuan Zhou
Summary: Protein S-acylation, also known as palmitoylation, is a vital lipid post-translational modification in eukaryotes, playing critical roles in plant development and responses to various stresses. The dynamic and reversible nature of S-acylation allows membrane-associated proteins to undergo cycling and trafficking, acting as a switch in signaling transductions. While numerous S-acylated proteins have been identified in plants, the understanding of the regulatory mechanisms controlling this process remains incomplete.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Zishuo Chen, Minkai Song, Ting Wang, Jiawen Gao, Fei Lin, Hui Dai, Chao Zhang
Summary: This review provides a detailed overview of the ubiquitination role of circular RNA (circRNA) in the regulation mechanism of various diseases, and discusses its potential significance in disease diagnosis and prognosis.
Article
Biochemistry & Molecular Biology
Ali Asli, Sabreen Higazy-Mreih, Meirav Avital-Shacham, Mickey Kosloff
Summary: The study compared RGS domains across the family and identified key interactions between RGS residues and G alpha switch regions. Modulatory and disruptor residues selectively modulated RGS activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biology
Alexander S. Hauser, Charlotte Avet, Claire Normand, Arturo Mancini, Asuka Inoue, Michel Bouvier, David E. Gloriam
Summary: Two-thirds of human hormones and one-third of clinical drugs act on membrane receptors coupled to G proteins, but there are differences in the reported G protein couplings among recent large-scale datasets. This study presents a common coupling map that uncovers novel couplings, GPCR-G protein selectivity, and the comparison of co-coupling and co-expression of G proteins with phylogenetic relationships. These findings will advance receptor research and cellular signaling, and contribute to the development of safer drugs.
Article
Plant Sciences
Jun Takeuchi, Kosuke Fukui, Yoshiya Seto, Yousuke Takaoka, Masanori Okamoto
Summary: Small-molecule plant hormones play a crucial role in controlling plant growth, development, differentiation, and environmental responses. Through genomic decoding of model plants with genetic mutants, scientists have elucidated the molecular mechanisms of nine types of plant hormones and identified the structure of hormone receptors. Studies on the three-dimensional structure of ligand-receptor complexes have revealed the details of ligand perception mechanisms.
Article
Multidisciplinary Sciences
Dia A. Ghose, Kaitlyn E. Przydzial, Emily M. Mahoney, Amy E. Keating, Michael T. Laub
Summary: The evolution of novel functions in biology relies on gene duplication and divergence, creating large paralogous protein families. However, the specificity of these paralogs to their interaction partners can be sensitive to mutation. Through deep mutational scanning, it was demonstrated that a family of bacterial signaling proteins exhibits marginal specificity, with individual substitutions leading to substantial cross-talk between pathways. These findings suggest that the evolution of bacterial signaling proteins is constrained by sequence space crowding, and that evolution selects for good enough rather than optimized phenotypes in paralogs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Hanrui Liu, Toni A. Baeumler, Kai Nakamura, Yuga Okada, Seojung Cho, Akihiro Eguchi, Daisuke Kuroda, Kouhei Tsumoto, Ryosuke Ueki, Shinsuke Sando
Summary: Cell membrane receptors play a crucial role in regulating cellular responses by detecting and transducing extracellular signals. Receptor engineering allows for directing cells to respond to specific external cues and perform programmed functions. This study introduces an aptamer-based signal transduction system that enables control and customization of engineered receptor functions.
Review
Microbiology
Yunqiang Chen, Yuheng Shi, Jing Wu, Nan Qi
Summary: MAVS functions as a crucial switch in immune signal transduction against RNA viruses, forming aggregates upon viral infection to activate interferon signaling and maintain immune homeostasis. Viruses and hosts target MAVS for regulation, with researchers focusing on post-translational modifications like ubiquitination and phosphorylation.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Ji Liu, Jinhan Sheng, Leihou Shao, Qizhen Zheng, Wenting Li, Xianghan Chen, Lanqun Mao, Ming Wang
Summary: Hierarchical self-assembly of TPE-featured metal-organic cages and beta-cyclodextrin-conjugated polyethylenimine generates fluorescent supramolecular nanoparticles (FSNPs) for efficient protein delivery into neural cells, allowing rapid release into the cytosol for subcellular targeting. Delivery of molecular chaperone DJ-1 using FSNPs activates MAPK/ERK signaling in neural cells to protect cells from oxidative stress.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Naoya Kawakami, Hiroki Sato, Naohiro Terasaka, Kunio Matsumoto, Hiroaki Suga
Summary: The researchers have developed a ubiquitin-based protein ligand multimer, called U-bodies, as a surrogate agonist for the MET receptor. These U-body constructs have high binding affinity, thermal stability, and proteolytic stability. By assembling them into dimeric, tetrameric, and octameric structures, potent MET activation and cell proliferation-promoting activities are achieved.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Engineering, Biomedical
Aysegul Dede Eren, Steven Vermeulen, Tara C. Schmitz, Jasper Foolen, Jan de Boer
Summary: Cells and their surrounding extracellular matrix (ECM) participate in dynamic reciprocity to maintain tissue homeostasis. This involves the deposition of ECM by cells, which then presents the signals that define cell identity. The relationship between cell shape, ECM, and tissue homeostasis is important for understanding pathological conditions and for manipulating cell function in micro-fabricated platforms. This manuscript discusses the loop of phenotype in tendon tissue homeostasis, focusing on cell shape, ECM organization, and signal transduction pathways.
ACTA BIOMATERIALIA
(2023)
Review
Oncology
Keesha E. Erickson, Oleksii S. Rukhlenko, Richard G. Posner, William S. Hlavacek, Boris N. Kholodenko
SEMINARS IN CANCER BIOLOGY
(2019)
Article
Biochemical Research Methods
Keesha E. Erickson, Oleksii S. Rukhlenko, Md Shahinuzzaman, Kalina P. Slavkova, Yen Ting Lin, Ryan Suderman, Edward C. Stites, Marian Anghel, Richard G. Posner, Dipak Barua, Boris N. Kholodenko, William S. Hlavacek
PLOS COMPUTATIONAL BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Susan A. Kennedy, Mohamed-Ali Jarboui, Sriganesh Srihari, Cinzia Raso, Kenneth Bryan, Layal Dernayka, Theodosia Charitou, Manuel Bernal-Llinares, Carlos Herrera-Montavez, Aleksandar Krstic, David Matallanas, Max Kotlyar, Igor Jurisica, Jasna Curak, Victoria Wong, Igor Stagljar, Thierry LeBihan, Lisa Imrie, Priyanka Pillai, Miriam A. Lynn, Erik Fasterius, Cristina Al-Khalili Szigyarto, James Breen, Christina Kiel, Luis Serrano, Nora Rauch, Oleksii Rukhlenko, Boris N. Kholodenko, Luis F. Iglesias-Martinez, Colm J. Ryan, Ruth Pilkington, Patrizia Cammareri, Owen Sansom, Steven Shave, Manfred Auer, Nicola Horn, Franziska Klose, Marius Ueffing, Karsten Boldt, David J. Lynn, Walter Kolch
NATURE COMMUNICATIONS
(2020)
Review
Chemistry, Multidisciplinary
Niels Hadrup, Vadim Zhernovkov, Nicklas Raun Jacobsen, Carola Voss, Maximilian Strunz, Meshal Ansari, Herbert B. Schiller, Sabina Halappanavar, Sarah S. Poulsen, Boris Kholodenko, Tobias Stoeger, Anne Thoustrup Saber, Ulla Vogel
Article
Biology
Alfonso Bolado-Carrancio, Oleksii S. Rukhlenko, Elena Nikonova, Mikhail A. Tsyganov, Anne Wheeler, Amaya Garcia-Munoz, Walter Kolch, Alex von Kriegsheim, Boris N. Kholodenko
Article
Nanoscience & Nanotechnology
Carole Seidel, Vadim Zhernovkov, Hilary Cassidy, Boris Kholodenko, David Matallanas, Frederic Cosnier, Laurent Gate
Summary: Inhalation of multi-walled carbon nanotubes (MWCNTs) induces lung inflammation, with different morphologies of CNTs showing varying toxicological effects. Long-term exposure may result in persistent adverse effects.
Article
Biochemistry & Molecular Biology
Oleksii Rukhlenko, Boris N. Kholodenko, Walter Kolch
Summary: This passage discusses the importance of dynamic protein complexes in cellular signal transduction networks, and highlights the various methods used to understand these dynamics, revealing the crucial role of these dynamic processes in correct signal processing and modulation.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Editorial Material
Multidisciplinary Sciences
Boris N. Kholodenko, Mariko Okada
Article
Multidisciplinary Sciences
Sujoy Chatterjee, Shivraj M. Yabaji, Oleksii S. Rukhlenko, Bidisha Bhattacharya, Emily Waligurski, Nandini Vallavoju, Somak Ray, Boris N. Kholodenko, Lauren E. Brown, Aaron B. Beeler, Alexander R. Ivanov, Lester Kobzik, John A. Porco, Igor Kramnik
Summary: Macrophages play a crucial role in host immunity and tissue homeostasis, with different activation programs leading to distinct functions. Imbalance of M1 and M2 macrophages can perpetuate chronic inflammation. Rocaglates sensitize macrophages to combat bacterial pathogens more effectively, showing potential for immunomodulation.
Review
Oncology
Andrea Rocca, Boris N. Kholodenko
Summary: Omics technologies and targeted drugs are changing the landscape of clinical oncology by promising precision oncology. Systems biology helps reconstruct the complex behavior of biological systems and compute responses to perturbations, supporting the advancement of clinical and translational oncological research. Patient-specific biomarkers based on signaling networks' dynamical models can have greater prognostic value than conventional biomarkers.
Article
Multidisciplinary Sciences
Oleksii S. Rukhlenko, Melinda Halasz, Nora Rauch, Vadim Zhernovkov, Thomas Prince, Kieran Wynne, Stephanie Maher, Eugene Kashdan, Kenneth MacLeod, Neil O. Carragher, Walter Kolch, Boris N. Kholodenko
Summary: cSTAR is an approach for mapping cell states, modelling transitions between them, and predicting targeted interventions to convert cell fate decisions. It uses omics data as input, integrates signalling and phenotypic data, and provides new biological insights by simulating how cells manoeuvre in Waddington's landscape.
Article
Cell Biology
Boris N. Kholodenko, Walter Kolch, Oleksii S. Rukhlenko
Summary: Cell states are determined by core networks that control cell-wide networks. The cSTAR method quantifies causal connections and models how core networks influence cell phenotypes, enabling the conversion of pathological states back to physiologically normal states.
TRENDS IN CELL BIOLOGY
(2023)
Article
Biology
Oleksii S. Rukhlenko, Boris N. Kholodenko
Summary: This protocol outlines a process for modeling the nonlinear behavior of intracellular signaling pathways, utilizing methods such as sampling parameter space and analyzing steady state stability to capture overall dynamic behavior. The protocol allows identification of main qualitative features, bifurcation analysis, and determination of borders separating different dynamical regimes within 2D parametric planes.
Article
Cell Biology
Boris N. Kholodenko, Nora Rauch, Walter Kolch, Oleksii S. Rukhlenko
Summary: Drug resistance may be caused by the impact of network topology on signal transduction, with key factors including negative and positive feedback loops, but feedback loops alone cannot completely reactivate signal transduction. Complete signal reactivation requires at least two pathways connecting the inhibited upstream protein to downstream output. Drug-induced overexpression or target dimerization can restore or increase downstream pathway activity.
Article
Mathematical & Computational Biology
Daniel Lill, Oleksii S. Rukhlenko, Anthony James Mc Elwee, Eugene Kashdan, Jens Timmer, Boris N. Kholodenko
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2019)