Article
Biochemistry & Molecular Biology
Miguel A. Zaballos, Adrian Acuna-Ruiz, Marta Morante, Garcilaso Riesco-Eizaguirre, Piero Crespo, Pilar Santisteban
Summary: The study demonstrates that BRAF- and RAS-mutant thyroid cells respond differently to DEL-22379, which cannot be explained by the previously described mechanism of action of the inhibitor. Nonetheless, DEL-22379 exhibits significant anti-tumor effects against BRAF-mutant cells in vivo, while the anti-tumor effects are mild for RAS-mutant cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Luis F. Iglesias-Martinez, Nora Rauch, Kieran Wynne, Brendan McCann, Walter Kolch, Jens Rauch
Summary: RAF kinases are important in cancer, particularly the BRAFV600E mutants. Although potent kinase inhibitors exist, their effects vary in different cancer types and can even induce paradoxical RAF kinase activation. Enhanced dimerization between RAF1 and BRAF contributes to both paradoxical activation and drug resistance. Mapping the interactomes of RAF1 monomers, RAF1-BRAF, and RAF1-BRAFV600E dimers, we identified and quantified over 1,000 proteins. Additionally, we analyzed the effects of vemurafenib and sorafenib, two clinically used RAF inhibitors, and found overlapping core interactomes with distinct condition-specific differences. Understanding these dynamic interactome changes may provide insights into RAF signaling and resistance mechanisms.
Review
Genetics & Heredity
Ana Herrero, Piero Crespo
Summary: Signals transmitted through the RAS-ERK pathway play a crucial role in cancer-related cellular processes. RAS dimerization, especially at membrane microdomains, is essential for RAF activation and can be targeted pharmacologically to prevent tumorigenesis.
Article
Medicine, Research & Experimental
Raie T. Bekele, Amruta S. Samant, Amin H. Nassar, Jonathan So, Elizabeth P. Garcia, Catherine R. Curran, Justin H. Hwang, David L. Mayhew, Anwesha Nag, Aaron R. Thorner, Judit Borcsok, Zsofia Sztupinszki, Chong-Xian Pan, Joaquim Bellmunt, David J. Kwiatkowski, Guru P. Sonpavde, Eliezer M. Van Allen, Kent W. Mouw
Summary: The study identified RAF1 activation as a dependency in a subset comprising nearly 20% of urothelial tumors, suggesting that targeting RAF1-mediated signaling may represent a rational therapeutic strategy.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Xue Gao, Yijie Liu, Yuancheng Li, Hao Fan, Rong Wu, Rukang Zhang, Brandon Faubert, Yu-Ying He, Marc B. Bissonnette, Siyuan Xia, Dong Chen, Hui Mao, Titus J. Boggon, Jing Chen
Summary: Phospholipase A2, group VII (PLA2G7), through its product Lyso-PAF, selectively regulates cell proliferation and tumor growth potential in melanoma cells expressing mutant NRAS, but not cells expressing BRAF V600E.
Article
Multidisciplinary Sciences
Aline Chessel, Noemie De Croze, Maria Dolores Molina, Laura Taberner, Philippe Dru, Luc Martin, Thierry Lepage
Summary: During early development of the sea urchin embryo, ERK signalling is activated in mesodermal precursors through a cell-autonomous mechanism involving the transcriptional activation of the gene encoding KSR3. KSR3 is an allosteric activator of RAF and can activate ERK signalling independently of RAS in non-chordate metazoa. The findings provide insights into the evolution and co-option of the ERK signalling pathway.
NATURE COMMUNICATIONS
(2023)
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
Oncology
Sara J. Hamis, Yury Kapelyukh, Aileen McLaren, Colin J. Henderson, C. Roland Wolf, Mark A. J. Chaplain
Summary: The study developed a mechanistic mathematical model to describe the synergistic action of dabrafenib and trametinib on ERK activity in BRAFV600E-mutant melanoma cells, elucidating the molecular mechanism underlying vertical inhibition of the BRAF-MEK-ERK cascade.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Vlad-Adrian Afrasanie, Mihai-Vasile Marinca, Bogdan Gafton, Teodora Alexa-Stratulat, Alexandra Rusu, Eliza-Maria Froicu, Daniel Sur, Cristian Virgil Lungulescu, Larisa Popovici, Andrei-Vlad Lefter, Irina Afrasanie, Anca-Viorica Ivanov, Lucian Miron, Cristina Rusu
Summary: In this study, the frequency, distribution, coexistence, and clinicopathological and molecular correlations of RAS, BRAF, PIK3CA, and TP53 mutations were investigated in 104 patients with metastatic colorectal cancer from Northeastern Romania. TP53 was the most frequently mutated gene (73.1%), followed by KRAS (45.2%) and PIK3CA (6.7%). The study provides novel insights into genetic variations specific to the population from Northeastern Romania and enables the development of genetic profiles in a developing country with limited access to specialized genetic tests.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Joanne M. Munck, Valerio Berdini, Luke Bevan, Jessica L. Brothwood, Juan Castro, Aurelie Courtin, Charlotte East, Roberta Ferraldeschi, Tom D. Heightman, Christopher J. Hindley, Justyna Kucia-Tran, John F. Lyons, Vanessa Martins, Sandra Muench, Christopher W. Murray, David Norton, Marc O'Reilly, Michael Reader, David C. Rees, Sharna J. Rich, Caroline J. Richardson, Alpesh D. Shah, Lukas Stanczuk, Neil T. Thompson, Nicola E. Wilsher, Alison J-A Woolford, Nicola G. Wallis
Summary: ASTX029 is a highly potent and selective dual-mechanism ERK inhibitor that targets MAPK-activated cancers by inhibiting both ERK catalytic activity and phosphorylation by MEK. It has shown significant antitumor activity in both in vitro and in vivo models, including acquired resistance to MAPK pathway inhibitors. ASTX029 is currently undergoing evaluation in a clinical trial for patients with advanced solid tumors.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Haibo Xiong, Dandan Lu, Zhiyuan Li, Jianghao Wu, Xin Ning, Weijun Lin, Zechen Bai, Canhui Zheng, Yang Sun, Wei Chi, Lixin Zhang, Xiumei Xu
Summary: Plant growth is regulated by light and gibberellin (GA) signals, which have opposite effects on hypocotyl elongation. This study reveals that GA promotes hypocotyl elongation through the activation of ABI4. DELLAs interact with ABI4 and inhibit its DNA-binding activity, while ABI4 interacts with HY5, a key factor in light signaling, to regulate the expression of GA catabolism genes and modulate GA levels, thus controlling hypocotyl elongation.
PLANT COMMUNICATIONS
(2023)
Review
Oncology
Manuel Felipe Fernandez, Jacob Choi, Jeffrey Sosman
Summary: Immune checkpoint inhibitors and BRAF/MEK inhibitors are the main treatments for melanoma, but resistance to these therapies emphasizes the need for new treatment options. Monoclonal antibodies and small molecules allow targeted therapy by focusing on specific mediators of cancer. Melanoma has several driver mutations, and targeting them could lead to novel therapies.
Article
Chemistry, Multidisciplinary
Till Rudack, Christian Teuber, Marvin Scherlo, Joern Gueldenhaupt, Jonas Schartner, Mathias Luebben, Johann Klare, Klaus Gerwert, Carsten Koetting
Summary: Studying the Ras dimer structure has shown that inhibiting the dimerization of oncogenic Ras can suppress cancer cell growth. By incorporating unnatural amino acids into Ras and utilizing labeling methods, the accuracy of the dimer structure model can be validated.
Review
Pharmacology & Pharmacy
Yunli Huang, Yongqi Zhen, Yanmei Chen, Shaoguang Sui, Lan Zhang
Summary: This article provides a comprehensive review of the interplay between the RAS/RAF/MEK/ERK signaling pathway and autophagy, as well as their application in cancer therapy. The impact of small molecule inhibitors targeting this pathway on autophagy is discussed, and the advantages and limitations of combining these inhibitors with autophagy inhibitors are explored.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Cell Biology
Zigen Lin, Xiaozhu Tang, Yuhao Cao, Lijin Yang, Mingmei Jiang, Xinying Li, Jie Min, Bing Chen, Ye Yang, Chunyan Gu
Summary: CD229 plays an oncogenic role in multiple myeloma by promoting cell proliferation through regulating the RAS/ERK signaling pathway.
Article
Multidisciplinary Sciences
Marek Kochanczyk, Frederic Grabowski, Tomasz Lipniacki
ROYAL SOCIETY OPEN SCIENCE
(2020)
Article
Virology
Frederic Grabowski, Grzegorz Preibisch, Stanislaw Gizinski, Marek Kochanczyk, Tomasz Lipniacki
Summary: The novel SARS-CoV-2 Variant of Concern (VOC)-202012/01, known as B.1.1.7, first identified in the UK in September 2020, has rapidly spread globally and is of concern due to its potential impact on vaccine effectiveness. The VOC has acquired significant mutations, including some that may compromise the binding of neutralizing antibodies, and it is essential to monitor its molecular evolution to understand its impact on the ongoing pandemic.
Article
Multidisciplinary Sciences
Marek Kochanczyk, Tomasz Lipniacki
Summary: Countries worldwide are adopting strategies to minimize the socio-economic impact of the ongoing COVID-19 pandemic. Delay in implementing nationwide quarantine measures can lead to increased infections and deaths, which then require stringent and sustained lockdown measures for suppression. This highlights the correlation between mobility reduction and COVID-19-associated deaths, showing an illusion of a trade-off between death toll and economic loss.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Anna Hollosi, Katalin Paszty, Miklos Kellermayer, Guillaume Charras, Andrea Varga
Summary: Mechanical forces on cell-cell adhesion regulate barrier function of endothelial cells, with BRAF playing a crucial role in stress-induced responses. Actin cytoskeleton remodeling and intercellular gap formation are key factors influenced by external stresses, modulated by BRAF to potentially reverse decreased barrier function in blood vessels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Frederic Grabowski, Marek Kochanczyk, Tomasz Lipniacki
Summary: Omicron, a highly mutated variant of SARS-CoV-2, has rapidly spread and approached fixation in South Africa and has been detected worldwide. Its exponential growth and short doubling time may be attributed to its ability to evade immunity and infect both recovered and vaccinated individuals. The growth rate of Omicron compared to Delta is considerably higher, indicating a potential for larger epidemic outbreaks.
Article
Biochemical Research Methods
Robert C. Mines, Tomasz Lipniacki, Xiling Shen
Summary: This study investigates the effects of nucleosome-induced pausing on transcriptional dynamics by constructing an agent-based model. The results show that slow nucleosome unwrapping dynamics can induce the formation of RNAPII convoys, preventing nucleosome rebinding and leading to bursts of transcription.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna Hollosi, Katalin Paszty, Balint Levente Bunta, Tamas Bozo, Miklos Kellermayer, Marta Lidia Debreczeni, Laszlo Cervenak, Manuela Baccarini, Andrea Varga
Summary: The dynamics of actin cytoskeleton and its connection to endothelial cell-cell junctions play a crucial role in determining the barrier function of endothelial cells.
Article
Mathematics, Applied
M. Banerjee, T. Lipniacki, A. d'Onofrio, V. Volpert
Summary: This study investigates a strain-dependence SIR model with virus mutations and a continuous strain variable, and characterizes the epidemic progression of infected individuals through numerical simulations and analytical estimates. Different scenarios of epidemic progression are identified, and the occurrence of single outbreak or multiple outbreaks depends on the characteristics of the transmission rate.
COMMUNICATIONS IN NONLINEAR SCIENCE AND NUMERICAL SIMULATION
(2022)
Article
Virology
Maciej Czerkies, Marek Kochanczyk, Zbigniew Korwek, Wiktor Prus, Tomasz Lipniacki
Summary: Preinfection with respiratory syncytial virus (RSV) increases interferon beta (IFN-beta) production, providing higher-level protection against subsequent infection with respiratory syncytial virus than with influenza A virus (IAV). Sequential infection with RSV followed by IAV is crucial for cross-protection, dependent on IFN-beta and IFN-lambda signaling.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemical Research Methods
Pawel Nalecz-Jawecki, Paolo Armando Gagliardi, Marek Kochanczyk, Coralie Dessauges, Olivier Pertz, Tomasz Lipniacki
Summary: In this study, the authors investigated how living cells transfer information from membrane receptors to downstream proteins to respond to external stimuli. They found that the MAPK/ERK transduction pathway can receive at least 6 bits of information per hour, enabling rapid binary decisions to varied extracellular stimuli.
PLOS COMPUTATIONAL BIOLOGY
(2023)
