Article
Biochemistry & Molecular Biology
Nanami Ogino, Ryoma Masuda, Louvy Lynn Punzalan, Emi Yamashita, Shota Igaue, Yoshihisa Inoue, Junko Ohkanda
Summary: In this study, a series of FC derivatives were synthesized and their stabilization effects on the binding of 14-3-3 to phosphopeptides were evaluated. The results showed that introducing an amino group at a specific position on the glucoside moiety improves stabilization. Furthermore, 6' amino benzyl 21b exhibited higher antiproliferative activity.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Peter J. Cossar, Madita Wolter, Lars van Dijck, Dario Valenti, Laura M. Levy, Christian Ottmann, Luc Brunsveld
Summary: The study emphasizes the importance of considering the selectivity of stabilizer molecules in addition to their potency. Targeting the phosphorylated motifs on 14-3-3 hub proteins can lead to the stabilization of specific protein-protein interactions and drive selective PPI stabilization through cooperative complex formation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Kenta Tanaka, Yoshiya Hatano, Junko Ohkanda
Summary: The 14-3-3 family of proteins plays a central role in regulating signaling pathways driven by serine/threonine kinases. Although there are seven highly conserved isoforms of 14-3-3 in humans, the specific functions of each isoform are still not fully understood. This study focused on evaluating the sigma isoform of 14-3-3 and designing a fluorescent labeling agent using a natural product as a base. The results showed that the labeled agent exhibited selective fluorescent detection of 14-3-3 sigma, indicating its potential use for studying the biological roles of this isoform.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
William M. Marsiglia, Arthur Chow, Zaigham M. Khan, Liu He, Arvin C. Dar
Summary: This study presents a NanoBRET-based assay to quantify the direct target engagement of MEK inhibitors on MEK1 and its complexes with ARAF, BRAF, CRAF, KSR1 and KSR2 in living cells. The study reveals the preferences of MEK inhibitors among these complexes and their binding profiles. Furthermore, the assay can also report on the effect of pathogenic mutations on MEK inhibitor binding. These methods are important for screening compounds targeting specific complexes in the RAS-MAPK cascade.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Hayarpi Torosyan, Michael D. Paul, Antoine Forget, Megan Lo, Devan Diwanji, Krzysztof Pawlowski, Nevan J. Krogan, Natalia Jura, Kliment A. Verba
Summary: In this study, the cryo-EM structure of the PEAK3/14-3-3 complex was presented, revealing the asymmetric binding mode and the unique secondary interaction between PEAK3 and 14-3-3. It was also found that PKD regulates the binding of PEAK3 and 14-3-3, and disruption of this binding leads to nuclear enrichment of PEAK3 and distinct protein-protein interactions. The results demonstrate how 14-3-3 modulates PEAK3 localization and protein-protein interactions.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Tongwang Yang, Cunle Zhu, Ying Shi, Yuntai Shen, Yuxue Gao, Bowen Zhang, Rifeng Jin, Daojie Liu, Yabo Ouyang, Xiaoni Liu, Wenjing Wang, Pengxiang Yang, Qingguo Xu, Jinzhen Cai, Dexi Chen
Summary: ASPP2 promotes tumor suppression in hepatocellular carcinoma by activating the BRAF/MEK/ERK signaling pathway through the formation of an ASPP2/k18/14-3-3 ternary complex.
CANCER GENE THERAPY
(2022)
Review
Biochemistry & Molecular Biology
Mauro Marra, Lorenzo Camoni, Sabina Visconti, Anna Fiorillo, Antonio Evidente
Summary: This article outlines the research and mechanism of action of Fusicoccin, highlighting its impact on plant growth processes and potential roles in animals. The ability of Fusicoccin to stimulate fundamental plant processes by activating certain proteins and producing biological effects is a key focus of the study.
Article
Neurosciences
Rodrigo Vinueza-Gavilanes, Jorge Juan Bravo-Gonzalez, Leyre Basurco, Chiara Boncristiani, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Irene Marcilla, Alberto Perez-Mediavilla, Maria Rosario Luquin, Africa Vales, Gloria Gonzalez-Aseguinolaza, Maria Soledad Aymerich, Tomas Aragon, Montserrat Arrasate
Summary: This study identified 14-3-3 epsilon as a common protein interactor for alpha-synuclein and found that stabilization of this interaction can reduce alpha-synuclein toxicity. Furthermore, treatment with Fusicoccin-A protected dopaminergic neuronal somas in a Parkinson's disease mouse model. These findings suggest that 14-3-3 epsilon and Fusicoccin-A could be potential therapeutic targets for synucleinopathies.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Yinjie Guo, Qiuxin Li, Daili Ji, Lijin Tian, Joerg Meurer, Wei Chi
Summary: This study developed a ubiquitin-based module capable of modifying multiprotein complexes in plant chloroplasts. The researchers successfully modified the Photosystem II complex and discovered that the interaction between its components affects leaf development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Biomedical
Minghai Chen, Chuang Yan, Yingxin Ma, Xian-En Zhang
Summary: The tandem near-infrared BiFC (tBiFC) system constructed in this study using a split near-infrared phytochrome IFP2.0 provides a bright and high fluorescence intensity tool for visualizing protein-protein interactions in live cells and living mice. Compared to previous near-infrared BiFC systems, the tBiFC system shows significantly increased signal intensity for both weak and strong protein-protein interactions in living cells, as well as in live mice imaging.
Article
Biology
Pavel Pohl, Rohit Joshi, Olivia Petrvalska, Tomas Obsil, Veronika Obsilova
Summary: The study investigated the structural basis of Nedd4-2 regulation by 14-3-3 and identified phosphorylated Ser342 and Ser448 as key residues facilitating 14-3-3 binding. The Nedd4-2:14-3-3 complex induces a structural rearrangement of Nedd4-2 by inhibiting interactions between its structured domains.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Morgan R. Packer, Jillian A. Parker, Jean K. Chung, Zhenlu Li, Young Kwang Lee, Trinity Cookis, Hugo Guterres, Steven Alvarez, Md Amin Hossain, Daniel P. Donnelly, Jeffrey N. Agar, Lee Makowski, Matthias Buck, Jay T. Groves, Carla Mattos
Summary: Studies demonstrate that Raf-Ras binding domain (Raf-RBD) can induce Ras dimerization at low surface densities and in solution, with robust connections between two Raf-RBD D113 residues confirmed by molecular dynamics simulations. These results suggest that Raf-RBD binding and Ras dimerization occur together, forming a high-affinity signaling complex.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Claire C. Munier, Christian Ottmann, Matthew W. D. Perry
Summary: The 14-3-3 proteins play crucial roles in regulating the inflammatory response at genetic, molecular, and cellular levels. They affect key components of the immune response and can lead to clinical syndromes when their recognition processes are disrupted. Abnormal levels of 14-3-3 contribute to undesirable immune responses and chronic inflammatory conditions.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Michael J. Roy, Minglyanna G. Surudoi, Ashleigh Kropp, Jianmei Hou, Weiwen Dai, Joshua M. Hardy, Lung-Yu Liang, Thomas R. Cotton, Bernhard C. Lechtenberg, Toby A. Dite, Xiuquan Ma, Roger J. Daly, Onisha Patel, Isabelle S. Lucet
Summary: PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. The researchers elucidate the molecular details of key PEAK signaling interactions with the adapter proteins CrkII and Grb2 and the scaffold protein 14-3-3. They identify a conserved high affinity 14-3-3 motif on PEAK3 and demonstrate its role as a molecular switch to regulate CrkII binding and signaling via Grb2.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Bente A. Somsen, Fenna W. B. Craenmehr, Wei-Hong W. Liu, Auke A. Koops, Marloes A. M. Pennings, Emira J. Visser, Christian Ottmann, Peter J. Cossar, Luc Brunsveld
Summary: Molecular glues represent a novel approach in drug discovery, however, the targeted stabilization of protein complexes is still challenging due to a lack of drug design rules. This study demonstrates the successful development of a peptide-based molecular glue that selectively stabilizes the 14-3-3/ChREBP protein-protein interaction by utilizing the functional mapping of hotspots.
