Article
Biochemistry & Molecular Biology
Farid A. Siddiqui, Vladimir Vukic, Tiina A. Salminen, Daniel Abankwa
Summary: Elaiophylin is a macrodiolide that disrupts the interaction between Hsp90 and Cdc37, selectively targeting K-Ras and inhibiting cancer stem cell properties. This mechanism is similar to conglobatin A and leads to decreased expression of Hsp90 client HIF1 alpha, resulting in potent effects on cancer cell formation.
Article
Biochemistry & Molecular Biology
Dhirendra K. Simanshu, Mark R. Philips, John F. Hancock
Summary: One open question in RAS biology is the existence and role of RAS dimers in RAF dimerization and activation. The hypothesis of RAS dimers arose from the discovery of RAF kinases functioning as obligate dimers, suggesting that G-domain-mediated RAS dimerization might nucleate RAF dimer formation. This review presents evidence on RAS dimerization and discusses a recent consensus among RAS researchers that the clustering of multiple RAS proteins is not due to the stable association of G-domains, but rather to the membrane phospholipids and RAS C-terminal membrane anchors.
Article
Chemistry, Applied
Liliane S. F. Leite, Francys K. V. Moreira, Luiz H. C. Mattoso, Julien Bras
Summary: Adjusting pH, CNCs content, and film-forming drying temperature is an effective strategy for improving the physical properties of Gel/CNCs films. Electrostatic attractive forces can reduce water vapor permeability, while the formation of complex coacervates may decrease mechanical properties.
FOOD HYDROCOLLOIDS
(2021)
Article
Chemistry, Multidisciplinary
Qingxin Zhang, Haitao Lei, Hongbo Guo, Yabo Wang, Yimei Gao, Wei Zhang, Rui Cao
Summary: Research has shown that the electrocatalytic HER activities of Cu porphyrins significantly decrease when positively charged substituents are located close to the Cu ion, while Cu porphyrin with negatively charged substituents outperforms others under the same conditions.
Article
Chemistry, Medicinal
Hongling Zhou, Youfang Gan, Yuanyuan Li, Xiaoqian Chen, Yuyang Guo, Rui Wang
Summary: Protein degradation is an effective strategy to modulate protein functions and cellular signaling pathways. A chemically catalyzed PROTAC approach was developed to induce the degradation of RAS protein through post-translational prenyl modification. This method successfully degraded RAS protein in multiple cancer cell lines, expanding the PROTAC toolsets for studying disease-relevant protein targets.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biophysics
Van A. Ngo, Angel E. Garcia
Summary: Molecular dynamics simulations revealed that KRas dimers exhibit multiple conformations, with some involving HVR and α(2) helix, potentially mediating dimerization. Certain dimer configurations may contribute to the recruitment of cytosolic Raf kinases, while a variant of the dimer interface similar to HRas was identified.
BIOPHYSICAL JOURNAL
(2022)
Article
Food Science & Technology
Yousra Abid, Chedia Ben Amara, Houda Gharsallah, Emilie Dumas, Nour-Eddine Chihib, Hamadi Attia, Samia Azabou, Adem Gharsallaoui
Summary: This study found that anionic EPS and cationic nisin formed complexes through electrostatic interactions in a model solution at pH 5.0. EPS-GM was able to form larger and more complexes with nisin, which interestingly did not affect nisin's antimicrobial activity and may act as protective agents for nisin when used in foods. These results could help optimize the physicochemical conditions for food products containing EPS.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Qingxin Zhang, Haitao Lei, Hongbo Guo, Yabo Wang, Yimei Gao, Wei Zhang, Rui Cao
Summary: This study investigates the effects of positively charged substituents on the hydrogen evolution reaction and finds that this effect can improve the activity and selectivity of the CO2 reduction reaction. This provides insights for the design of HER catalysts and has important implications for the design of catalysts for CO2RR.
Review
Biochemistry & Molecular Biology
Arathi Nair, Katharina F. Kubatzky, Bhaskar Saha
Summary: The Ras GTPase plays a central role in oncogenic circuitry, with its isoforms H-, K-, and N-Ras exhibiting functional differences and cell type-specific activities. The preferential localization of different Ras isoforms in various cellular compartments adds a new dimension to isoform-specific signaling and diverse functions. Therefore, considering isoform-specific properties in the design of therapeutic strategies is crucial for effective treatments in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Andreas Weiss, Edwige Lorthiois, Louise Barys, Kim S. Beyer, Claudio Bomio-Confaglia, Heather Burks, Xueying Chen, Xiaoming Cui, Ruben de Kanter, Lekshmi Dharmarajan, Carmine Fedele, Marc Gerspacher, Daniel Alexander Guthy, Victoria Head, Ashley Jaeger, Eloisa Jimenez Nunez, Jeffrey D. Kearns, Catherine Leblanc, Sauveur-Michel Maira, Jason Murphy, Helen Oakman, Nils Ostermann, Johannes Ottl, Pascal Rigollier, Danielle Roman, Christian Schnell, Richard Sedrani, Toshio Shimizu, Rowan Stringer, Andrea Vaupel, Hans Voshol, Peter Wessels, Toni Widmer, Rainer Wilcken, Kun Xu, Frederic Zecri, Anna F. Farago, Simona Cotesta, Saskia M. Brachmann
Summary: JDQ443 is a structurally unique covalent inhibitor of KRAS(G12C) that demonstrates potent and selective antitumor activity in cell lines and in vivo models. In preclinical models and patients with KRAS(G12C)-mutated malignancies, JDQ443 shows potent antitumor activity as monotherapy and in combination with the SHP2 inhibitor TNO155.
Article
Biochemistry & Molecular Biology
Yuanhao Wang, Dong Ji, Chaoyu Lei, Yingfei Chen, Yuran Qiu, Xinyi Li, Mingyu Li, Duan Ni, Jun Pu, Jian Zhang, Qiang Fu, Yaqin Liu, Shaoyong Lu
Summary: The dual phosphorylation of K-Ras induces structural changes affecting nucleotide and catalytic sites, reducing the catalytic competence and signal delivery abilities of GAP, SOS, and Raf. Phosphorylation also disrupts the Ras/Raf interface allosteric pathway, altering the distribution of Ras-GTP sub-states and identifying potential druggable pockets. These findings highlight the impact of phosphorylation on Ras function and signal transduction, suggesting it as a target for cancer drug discovery.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Multidisciplinary Sciences
Goodwin G. Jinesh, Marco Napoli, Marian T. Smallin, Andrew Davis, Hayley D. Ackerman, Payal Raulji, Nicole Montey, Elsa R. Flores, Andrew S. Brohl
Summary: This study revealed that overexpression of C19MC miRNA is linked to p53 defects in hepatocellular carcinoma, leading to increased expression of MAGEA. Additionally, IFN-gamma and specific metals such as nickel and zinc play roles in regulating MAGEA expression and cell survival pathways.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Masaya Hagiwara, Hisataka Maruyama, Masakazu Akiyama, Isabel Koh, Fumihito Arai
Summary: The study demonstrates that actively remodeling the cellular microenvironment can modulate the force exerted on cells by ECM, influencing the directionality of collective cell migration and pattern formation. Using microfabrication techniques, optical tweezers, and mathematical models, the research confirms the presence of this mechanism.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Applied
Yuxiao Wang, Mo Li, Xin Wen, Haiteng Tao, Kunli Wang, Rao Fu, Hongxun Tao, Fuying Wang, Nan Chen, Yuanying Ni
Summary: This study explored a green and rapid strategy to engineer robust nanoemulsions using electrostatic complexes of whey protein isolate (WPI) and chondroitin sulfate (CS) induced by ultrasonication and acidic conditions. The optimized CS:WPI ratio of 4:6 resulted in nanoemulsions with desired particle size and high crystallinity.
FOOD HYDROCOLLOIDS
(2023)
Article
Cell Biology
Nina Kozar-Gillan, Atanaska Velichkova, George Kanatouris, Yael Eshed-Eisenbach, Gavin Steel, Martine Jaegle, Eerik Aunin, Elior Peles, Carole Torsney, Dies N. N. Meijer
Summary: This study reveals a novel molecular pathway involving LGI3/2-ADAM23 interactions that cluster and stabilize Shaker-type voltage-gated potassium channels (Kv1) in myelinated axons. These myelin concealed Kv1 channels play a significant role in modifying axonal physiology.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Cell Biology
Amelia L. Parker, Wee Siang Teo, Simon Brayford, Ullhas K. Moorthi, Senthil Arumugam, Charles Ferguson, Robert G. Parton, Joshua A. McCarroll, Maria Kavallaris
Summary: Beta III-tubulin, aberrantly expressed in epithelial cancers, impacts mitochondrial volume and shape through its C-terminal tail. It interacts specifically with regulators of mitochondrial dynamics and promotes a dynamic and extended mitochondrial network. The regulatory role of Beta III-tubulin in mitochondrial network dynamics has implications for maintaining mitochondrial homeostasis in health and disease.
Editorial Material
Multidisciplinary Sciences
Robert G. Parton, Brett M. Collins
Summary: The structure of caveolin, the major membrane protein of caveolae, is revealed by cryo-electron microscopy, providing new insights into its functions.
Article
Cell Biology
Danyon Harkins, Tracey J. Harvey, Cooper Atterton, Ingrid Miller, Laura Currey, Sabrina Oishi, Maria Kasherman, Raul Ayala Davila, Lucy Harris, Kathryn Green, Hannah Piper, Robert G. Parton, Stefan Thor, Helen M. Cooper, Michael Piper
Summary: The transcription factor NFIX plays a pivotal role in the regulation of cell adhesion within ependymal cells of the lateral ventricles, with Nfix(-/-) mice exhibiting abnormal cilia structure and disrupted localization of adhesion proteins.
Review
Pharmacology & Pharmacy
Gareth Griffiths, Jean Gruenberg, Mark Marsh, Jens Wohlmann, Arwyn T. Jones, Robert G. Parton
Summary: Nanoparticles are promising for delivering drugs, proteins, and nucleic acids into cells. The development and application of nanoparticles involve scientists from various fields who design, fabricate, and characterize nanoparticles in vitro. However, the research on the interactions between nanoparticles and cells in the field of cell biology is often of sub-standard quality.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Correction
Cell Biology
Paulina Moreno-Layseca, Niklas Z. Jantti, Rashmi Godbole, Christian Sommer, Guillaume Jacquemet, Hussein Al-Akhrass, James R. W. Conway, Pauliina Kronqvist, Roosa E. Kallionpaa, Leticia Oliveira-Ferrer, Pasquale Cervero, Stefan Linder, Martin Aepfelbacher, Henrik Zauber, James Rae, Robert G. Parton, Andrea Disanza, Giorgio Scita, Satyajit Mayor, Matthias Selbach, Stefan Veltel, Johanna Ivaska
NATURE CELL BIOLOGY
(2022)
Article
Cell Biology
Elin Larsson, Bjoern Moren, Kerrie-Ann McMahon, Robert G. Parton, Richard Lundmark
Summary: Research reveals that the large GTPase dynamin 2 does not mediate caveolae fission from the plasma membrane, as previously thought. Instead, dynamin 2 associates with a subset of caveolae and restrains their presence on the plasma membrane via a GTPase-independent mechanism.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Cell Biology
Leeba Ann Chacko, Felix Mikus, Nicholas Ariotti, Gautam Dey, Vaishnavi Ananthanarayanan
Summary: Association of microtubules with mitochondria is crucial for determining cell division symmetry in fission yeast. Mutant cells with enhanced or no attachment of mitochondria to microtubules exhibited aberrant dynamics, resulting in nuclear positioning errors and asymmetric cell division. This led to unequal distribution of mitochondria in daughter cells, with the one receiving more mitochondria growing faster. Overall, our findings demonstrate the existence of homeostatic feedback controls between mitochondria and microtubules in fission yeast, which directly impact mitochondrial partitioning and cell growth.
JOURNAL OF CELL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Junchen Liu, Ransome van der Hoeven, Walaa E. Kattan, Jeffrey T. Chang, Dina Montufar-Solis, Wei Chen, Maurice Wong, Yong Zhou, Carlito B. Lebrilla, John F. Hancock
Summary: The authors demonstrate that a specific subset of cell surface glycosphingolipids regulates the localization of KRAS protein on the plasma membrane, highlighting a potential therapeutic target for KRAS-driven oncogenesis. They show that oncogenic KRAS expression increases the reliance on aerobic glycolysis and affects the synthesis of glycosphingolipids, which in turn is critical for the localization and organization of KRAS on the plasma membrane. Depletion of these glycosphingolipids diminishes the oncogenic function of KRAS in pancreatic cancer models. This study expands the understanding of the Warburg effect and reveals a potential vulnerability with therapeutic implications.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Yeping Wu, Ye-Wheen Lim, Robert G. Parton
Summary: Oxidative stress is a common feature in many diseases, but cells have evolved complex mechanisms to respond to this stress. Recent studies suggest that oxidative stress can cause disassembly of caveolae, releasing caveola proteins that regulate redox balance in the cell. These studies highlight the crucial role of caveolae in maintaining cellular susceptibility to oxidative stress-induced cell death and in cellular homeostasis and wound healing.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Cell Biology
Yeping Wu, Ye-Wheen Lim, David A. Stroud, Nick Martel, Thomas E. Hall, Harriet P. Lo, Charles Ferguson, Michael T. Ryan, Kerrie-Ann McMahon, Robert G. Parton
Summary: Using quantitative whole-cell proteomics, researchers found that the oxidative stress response is the major pathway dysregulated in cells lacking the caveola structural protein CAVIN1. CAVIN1 deletion compromised sensitivity to oxidative stress and wound-induced reactive oxygen species accumulation, affecting regeneration. Oxidative stress triggered lipid peroxidation and caveolar disassembly, allowing release of CAVIN1 and direct interaction with NRF2, resulting in NRF2 degradation and resistance to lipid-peroxidation-induced ferroptosis in CAVIN1-null cells.
DEVELOPMENTAL CELL
(2023)
Review
Immunology
Remi Safi, Miguel Sanchez-Alvarez, Marta Bosch, Caroline Demangel, Robert G. Parton, Albert Pol
Summary: Microbes have developed strategies to exploit lipid droplets (LDs), which are major lipid storage organelles in eukaryotes, as a source of nutrients for host colonization. However, recent studies have shown that LDs possess protein-mediated antibiotic activity, which is upregulated in response to danger signals and sepsis. LDs may serve as a chokepoint utilized by the innate immune system to defend against intracellular pathogens.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Dhirendra K. Simanshu, Mark R. Philips, John F. Hancock
Summary: One open question in RAS biology is the existence and role of RAS dimers in RAF dimerization and activation. The hypothesis of RAS dimers arose from the discovery of RAF kinases functioning as obligate dimers, suggesting that G-domain-mediated RAS dimerization might nucleate RAF dimer formation. This review presents evidence on RAS dimerization and discusses a recent consensus among RAS researchers that the clustering of multiple RAS proteins is not due to the stable association of G-domains, but rather to the membrane phospholipids and RAS C-terminal membrane anchors.
Article
Multidisciplinary Sciences
Azelle Hawdon, Niall D. Geoghegan, Monika Mohenska, Anja Elsenhans, Charles Ferguson, Jose M. Polo, Robert G. Parton, Jennifer Zenker
Summary: The spatial sorting of RNA transcripts in mouse preimplantation embryos plays a crucial role in gene expression and cell fate determination. Basally directed RNA transport is facilitated by microtubules and lysosomes. Despite higher accumulation in basal regions, higher translation activity occurs at the dispersed apical RNA foci, demonstrating spatial heterogeneities in RNA subtypes, organelle interactions, and translation events. Biased inheritance of RNA transcripts and differential translation capacity regulate cell fate allocation during embryonic development.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Guillaume Longatte, Fabio Lisi, Xueqian Chen, James Walsh, Wenqian Wang, Nicholas Ariotti, Till Boecking, Katharina Gaus, J. Justin Gooding
Summary: Single molecule experiments have gained significant attention recently. Many of these studies involve encapsulating a single molecule into nanoscale containers. The encapsulation efficiency of single molecules is an important parameter to consider, and previous theories have focused on encapsulating single molecules into perfectly sized monodispersed containers. However, experimental nanocontainers often have a size distribution and may require encapsulating a single binding pair instead of a single molecule. This study extends the Poisson distribution theory to predict the encapsulation efficiency of two different molecules in an association equilibrium, taking into account the container size distribution and the effect of adsorption to the container.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Materials Science, Biomaterials
Hamish C. Craig, Yin Yao, Nicholas Ariotti, Mohan Setty, Rechana Remadevi, Michael M. Kasumovic, Rangam Rajkhowa, Aditya Rawal, Sean J. Blamires
Summary: This study used advanced spectroscopic and microscopic methods to investigate the structure and function of silk, and found that the mechanical properties and nanoscale void formations vary along a single fiber in wild and domesticated silkworm species. These voids contribute to temperature regulation within the silkworm cocoons.
JOURNAL OF MATERIALS CHEMISTRY B
(2022)