Article
Biochemistry & Molecular Biology
Alberto Fernandez-Medarde, Rocio Fuentes-Mateos, Rosula Garcia-Navas, Andrea Olarte-San Juan, Jose Maria Sanchez-Lopez, Antonio Fernandez-Medarde, Eugenio Santos
Summary: The study found that new inhibitors of the anthraquinone family shared related chemical structures and were able to target multiple RAS isoforms, inhibit RAS activation in cells, and suppress the growth of cancer cell lines with different RAS genes. Unlike commercially available anthraquinone inhibitors, the new marine anthraquinone inhibitors did not exhibit cardiotoxicity, suggesting their potential as stronger and clinically useful blockers of anthraquinone SOS GEF.
Review
Biochemistry & Molecular Biology
Christina Kiel, David Matallanas, Walter Kolch
Summary: RAS oncogenes, commonly mutated in human cancers, control various cellular functions and their signaling is altered in over half of human cancers. Recent efforts in detailed molecular studies, large-scale omics studies, and computational modeling are providing a comprehensive understanding of RAS signaling, paving the way for new mechanism-based therapies for RAS mutated cancers.
Editorial Material
Plant Sciences
Aisling Reilly, Angela Feechan
Summary: This article comments on a study that found the interaction between Guanine nucleotide exchange factors (GEFs) Monensin Sensitivity 1 (MON1) and the Blumeria hordei-secreted effector CSEP0162, which play a crucial role in components of plant immunity such as haustorial encasement formation and localized cell death.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Article
Chemistry, Medicinal
Hongyu Jiang, Yiqing Fan, Xia Wang, Jie Wang, Haifan Yang, Weizheng Fan, Chunlei Tang
Summary: SOS1 is a crucial guanine nucleotide exchange factor that activates Ras protein in cells. We designed and synthesized a series of quinazoline-based compounds, and evaluated their biological activities. Among them, comparable compounds I-2 (IC50 = 20 nM), I-5 (IC50 = 18 nM), and I-10 (IC50 = 8.5 nM) have kinase activity equivalent to BAY-293 (IC50 = 6.6 nM) against SOS1, and I-10 also has cell activity equivalent to BAY-293, providing a theoretical reference for further research on SOS1 inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Fa-An Chao, Srisathiyanarayanan Dharmaiah, Troy Taylor, Simon Messing, William Gillette, Dominic Esposito, Dwight Nissley, Frank McCormick, R. Andrew Byrd, Dhirendra K. Simanshu, Gabriel Cornilescu
Summary: This article investigates the influence of conformational dynamics of RAS proteins on their interactions with downstream effectors and explains and predicts the altered binding affinities of different mutants.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Biochemistry & Molecular Biology
Celine Dinet, Tam Mignot
Summary: Motile cells use a molecular mechanism involving small GTPases, regulators, and sensors to change their movement direction in response to environmental cues. Myxococcus xanthus is a model organism used to study the control of directed cell motility, where a unique small Ras GTPase system regulates the reversal frequency of cell movement. The interconnected protein networks involved in this process link the environmental signals to the downstream polarity control system.
Article
Oncology
Fernando C. Baltanas, Cynthia Mucientes-Valdivieso, L. Francisco Lorenzo-Martin, Natalia Fernandez-Parejo, Rosula Garcia-Navas, Carmen Segrelles, Nuria Calzada, Rocio Fuentes-Mateos, Jesus M. Paramio, Xose R. Bustelo, Eugenio Santos
Summary: Sos1 and Sos2 have overlapping roles in proliferation and survival in skin cells, with Sos1 focusing on the ERK pathway and Sos2 controlling the PI3K pathway. Sos2 plays a crucial role in regulating the population of epidermal stem cells.
Article
Oncology
Moon Hee Yang, Timothy H. Tran, Bethany Hunt, Rebecca Agnor, Christian W. Johnson, Bing Shui, Timothy J. Waybright, Jonathan A. Nowak, Andrew G. Stephen, Dhirendra K. Simanshu, Kevin M. Haigis
Summary: An allosteric network involving lysine 104 and residues in the switch-II domain is essential for KRAS oncogenicity, which could be utilized in the development of inhibitors targeting the activated oncoprotein.
Article
Optics
Deirdre Kilbane, Eva Prinz, Tobias Eul, Michael Hartelt, Anna-Katharina Mahro, Matthias Hensen, Walter Pfeiffer, Martin Aeschlimann
Summary: We have designed and experimentally demonstrated an optical switch that utilizes the interference of plasmonic modes in whispering gallery mode (WGM) antennas. By selectively exciting even and odd WGM modes through non-normal illumination, we are able to switch the plasmonic near field between opposite sides of the antenna within a wavelength range of 60 nm centered around 790 nm. This switching mechanism has been experimentally verified using photoemission electron microscopy (PEEM) and a tunable wavelength femtosecond laser source in the visible and infrared.
Article
Oncology
Carmela Gomez, Rosula Garcia-Navas, Fernando C. Baltanas, Rocio Fuentes-Mateos, Alberto Fernandez-Medarde, Nuria Calzada, Eugenio Santos
Summary: This study demonstrates the protective role of SOS1 deficiency in the development of CML and identifies it as a novel therapeutic target.
Article
Multidisciplinary Sciences
Evan M. Gordon, Roselyne J. Chauvin, Andrew N. Van, Aishwarya Rajesh, Ashley Nielsen, Dillan J. Newbold, Charles J. Lynch, Nicole A. Seider, Samuel R. Krimmel, Kristen M. Scheidter, Julia Monk, Ryland L. Miller, Athanasia Metoki, David F. Montez, Annie Zheng, Immanuel Elbau, Thomas Madison, Tomoyuki Nishino, Michael J. Myers, Sydney Kaplan, Carolina Badke D'Andrea, Damion V. Demeter, Matthew Feigelis, Julian S. B. Ramirez, Ting Xu, Deanna M. Barch, Christopher D. Smyser, Cynthia E. Rogers, Jan Zimmermann, Kelly N. Botteron, John R. Pruett, Jon T. Willie, Peter Brunner, Joshua S. Shimony, Benjamin P. Kay, Scott Marek, Scott A. Norris, Caterina Gratton, Chad M. Sylvester, Jonathan D. Power, Conor Liston, Deanna J. Greene, Jarod L. Roland, Steven E. Petersen, Marcus E. Raichle, Timothy O. Laumann, Damien A. Fair, Nico U. F. Dosenbach
Summary: Using precision fMRI methods, the study found that the classic homunculus of the motor cortex is interrupted by regions with distinct connectivity and function. These regions, called inter-effector regions, are connected to each other and to the cingulo-opercular network. The inter-effector regions lack movement specificity and co-activate during action planning and axial body movement. The study suggests the existence of a somato-cognitive action network (SCAN) in the motor cortex for whole-body action planning.
Article
Multidisciplinary Sciences
Xuehua Xu, Xi Wen, Amer Moosa, Smit Bhimani, Tian Jin
Summary: The study demonstrates the important role of CAPRI in mediating GPCR activation-induced Ras adaptation in human neutrophils. By reducing cell sensitivity, CAPRI enables neutrophils to chemotax through higher concentration gradients of chemoattractants.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Simona Catozzi, Camille Ternet, Alize Gourrege, Kieran Wynne, Giorgio Oliviero, Christina Kiel
Summary: This study reconstructed the downstream effector network of Ras, consisting of 2290 proteins connected by 19,080 binary protein-protein interactions. The study identified a high level of crosstalk among different effector classes and revealed novel functions of specific effector pathways through functional enrichment analysis.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Multidisciplinary Sciences
Allen K. Kim, Helen D. Wu, Takanari Inoue
Summary: The study successfully designed a molecular switch that can rapidly translocate to different cellular locations based on the activity of PKA. By arranging peptide sequences and testing different valence numbers, an efficient peptide switch was identified that exhibited dynamic translocation dependent on PKA activity.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Anthony J. Asmar, Shaun R. Abrams, Jenny Hsin, Jason C. Collins, Rita M. Yazejian, Youmei Wu, Jean Cho, Andrew D. Doyle, Samhitha Cinthala, Marleen Simon, Richard H. van Jaarsveld, David B. Beck, Laura Kerosuo, Achim Werner
Summary: This study uncovers a posttranslational pathway that controls cytoskeletal signaling circuits to coordinate ectodermal patterning and neurulation. A specific tissue-specific restriction of CDC42 signaling by a ubiquitin-based effector-to-inhibitor is essential for early face, brain, and skin formation. Loss of this pathway leads to defective ectodermal patterning and neurulation.
NATURE COMMUNICATIONS
(2023)
