Article
Biology
Anna Keppner, Miguel Correia, Sara Santambrogio, Teng Wei Koay, Darko Maric, Carina Osterhof, Denise Winter, Angele Clerc, Michael Stumpe, Frederic Chalmel, Sylvia Dewilde, Alex Odermatt, Dieter Kressler, Thomas Hankeln, Roland H. Wenger, David Hoogewijs
Summary: Spermatogenesis relies on the gene expression program driven by Adgb, where the absence of Adgb leads to male infertility and abnormal sperm shape. Adgb interacts with Sept10, and the absence of Adgb mislocalizes Sept10 in sperm, revealing the importance of Adgb in proper sperm head shaping and flagellum formation.
Article
Biotechnology & Applied Microbiology
Katarzyna Bogucka, Federico Marini, Sebastian Rosigkeit, Janine Schloeder, Helmut Jonuleit, Kerstin David, Margarita Schlackow, Krishnaraj Rajalingam
Summary: KRAS is frequently mutated in lung cancers, making it a prime target for treatment. This study reveals that ERK3 plays a necessary role in KRAS-mediated NSCLC tumors, with its kinase activity required for KRAS-driven oncogenesis. Inhibitors targeting ERK3 kinase may be pursued for treating KRAS G12C-driven tumors.
CANCER GENE THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Mouna Ghorbel, Kaouthar Feki, Sana Tounsi, Najla Haddaji, Moez Hanin, Faical Brini
Summary: The catalytic activity of durum wheat catalase 1 (TdCAT1) is enhanced by various divalent cations and CaM in a Ca-dependent manner, which may play a crucial role in cellular response to oxidative stress.
Article
Biochemistry & Molecular Biology
Andrew C. Hedman, Zhigang Li, Laetitia Gorisse, Swetha Parvathaneni, Chase J. Morgan, David B. Sacks
Summary: AMP-activated protein kinase (AMPK) is crucial in maintaining cellular energy homeostasis through regulating catabolic and anabolic pathways, with IQGAP1 identified as a novel regulator of AMPK signaling. Lack of IQGAP1 leads to impaired AMPK activation and metabolic dysregulation, highlighting the importance of the functional interplay between IQGAP1 and AMPK.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Immunology
Prarthana J. Dalal, David P. Sullivan, Evan W. Weber, David B. Sacks, Matthias Gunzer, Isabella M. Grumbach, Joan Heller Brown, William A. Muller
Summary: The research highlights the important roles of endothelial CaM and CaMKIIδ in transducing specific calcium signals required for TEM, which interferes with the delivery of the lateral border recycling compartment (LBRC) and reduces TEM.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Giovanna Nalesso, Anne-Sophie Thorup, Suzanne Elizabeth Eldridge, Anna De Palma, Amanpreet Kaur, Kiran Peddireddi, Kevin Blighe, Sharmila Rana, Bryony Stott, Tonia Louise Vincent, Bethan Lynne Thomas, Jessica Bertrand, Joanna Sherwood, Antonella Fioravanti, Costantino Pitzalis, Francesco Dell'Accio
Summary: The WNT/CaMKII signaling pathway plays a crucial role in osteoarthritis by affecting the expression of markers such as HMOX1 and Sox-9. Inhibition of CaMKII may exacerbate cartilage damage and bone remodeling, while also upregulating the expression of matrix remodeling enzymes in articular chondrocytes. These findings suggest the potential therapeutic implications of targeting the WNT/CaMKII pathway in osteoarthritis.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Mengdie Feng, Xueqin Xie, Guoqiang Han, Tiantian Zhang, Yashu Li, Yicun Li, Rong Yin, Qifan Wang, Tong Zhang, Peipei Wang, Jin Hu, Ying Cheng, Zhuying Gao, Jing Wang, Jiwei Chang, Manman Cui, Kexin Gao, Jihua Chai, Weidong Liu, Chengli Guo, Shaoguang Li, Lingbo Liu, Fuling Zhou, Jianjun Chen, Haojian Zhang
Summary: The study highlights the critical role of YBX1 in maintaining myeloid leukemia cell survival in an m(6)A-dependent manner. YBX1 interacts with IGF2BPs to stabilize m(6)A-tagged RNA, and its deficiency dysregulates the expression of apoptosis-related genes and promotes mRNA decay of MYC and BCL2, contributing to defective survival in leukemia cells. Targeting YBX1 therapeutically may have implications for treating myeloid leukemia.
Article
Biochemistry & Molecular Biology
Lise C. Noack, Vincent Bayle, Laia Armengot, Frederique Rozier, Adiilah Mamode-Cassim, Floris D. Stevens, Marie-Cecile Caillaud, Teun Munnik, Sebastien Mongrand, Roman Pleskot, Yvon Jaillais
Summary: Phosphoinositides, specifically phosphatidylinositol 4-phosphate (PI4P), play a crucial role in membrane identity acquisition, particularly at the plant plasma membrane. PI4K alpha 1 is anchored to the plasma membrane through a complex involving proteins from various families, and is essential for pollen, embryonic, and post-embryonic development. The immobilization of the PI4K alpha 1 complex in plasma membrane nanodomains is critical for its function, highlighting the importance of lipid kinases in plasma membrane nanopatterning.
Article
Biology
Claudia N. Spaan, Ruben J. de Boer, Wouter L. Smit, Jonathan H. M. van derMeer, Manon van Roest, Jacqueline L. M. Vermeulen, Pim J. Koelink, Marte A. J. Becker, Simei Go, Joana Silva, William J. Faller, Gijs R. van den Brink, Vanesa Muncan, Jarom Heijmans
Summary: This study found that mutations in APC are often followed by mutations in oncogene KRAS in the development of colorectal cancer, and the latter changes cellular metabolism and is associated with the Warburg phenomenon. The researchers hypothesize that targeting Grp78 in AK-mutant intestines interferes with the metabolic phenotype imposed by Kras mutations. They found that Grp78 plays a critical role in Kras-mutated adenomagenesis, possibly through its involvement in GLUT1 expression and localization, affecting glycolysis and the Warburg effect.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemistry & Molecular Biology
Julie Schnipper, Sana Kouba, Frederic Hague, Alban Girault, Pierre Rybarczyk, Marie-Sophie Telliez, Stephanie Guenin, Riad Tebbakha, Henri Sevestre, Ahmed Ahidouch, Stine Falsig Pedersen, Halima Ouadid-Ahidouch
Summary: TRPC1 is upregulated in PDAC tissue and PANC-1 cell line, contributing to cell proliferation and spheroid growth. It interacts with PI3K-p85α and CaM to regulate cell cycle.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Han Byeol Lee, Si Hyoung Park, Chang-Ro Lee
Summary: This study revealed how the essential inner membrane protein YejM regulates LapB; the transmembrane domain of LapB interacts with YejM and inhibits its function, leading to the accumulation of LpxC. Additionally, LapB's transmembrane domain is crucial for both its physical interaction with YejM and its role in cold stress adaptation.
JOURNAL OF MICROBIOLOGY
(2021)
Article
Oncology
Rafael G. Amado, Michael Wolf, Marc Peeters, Eric Van Cutsem, Salvatore Siena, Daniel J. Freeman, Todd Juan, Robert Sikorski, Sid Suggs, Robert Radinsky, Scott D. Patterson, David D. Chang
Summary: The purpose of this study is to determine the impact of KRAS gene mutations on the efficacy of panitumumab monotherapy for metastatic colorectal cancer (mCRC). Through testing on 463 patients, it was found that 43% of patients had KRAS mutations. The results showed that panitumumab significantly improved overall survival and progression-free survival for patients with wild-type KRAS, while no significant efficacy was observed for patients with KRAS mutations. Therefore, KRAS status should be taken into account when selecting mCRC patients for panitumumab monotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Carolyn Nicole Brown, Nicole L. Rumian, Jonathan E. Tullis, Steven J. Coultrap, K. Ulrich Bayer
Summary: A beta shares similarity with the CaMKII regulatory domain, but does not directly affect CaMKII function. The impairment of CaMKII induced by A beta at synapses is mediated by indirect signaling events.
Article
Genetics & Heredity
Arafath K. Najumudeen, Fatih Ceteci, Sigrid K. Fey, Gregory Hamm, Rory T. Steven, Holly Hall, Chelsea J. Nikula, Alex Dexter, Teresa Murta, Alan M. Race, David Sumpton, Nikola Vlahov, David M. Gay, John R. P. Knight, Rene Jackstadt, Joshua D. G. Leach, Rachel A. Ridgway, Emma R. Johnson, Colin Nixon, Ann Hedley, Kathryn Gilroy, William Clark, Sudhir B. Malla, Philip D. Dunne, Giovanny Rodriguez-Blanco, Susan E. Critchlow, Agata Mrowinska, Gaurav Malviya, Dmitry Solovyev, Gavin Brown, David Y. Lewis, Gillian M. Mackay, Douglas Strathdee, Saverio Tardito, Eyal Gottlieb, Zoltan Takats, Simon T. Barry, Richard J. A. Goodwin, Josephine Bunch, Martin Bushell, Andrew D. Campbell, Owen J. Sansom
Summary: Colorectal tumors with mutated KRAS and APC rely on the amino acid transporter SLC7A5 for tumorigenesis and enhanced protein synthesis. Targeting SLC7A5 could be an attractive approach for therapy-resistant KRAS-mutant colorectal cancer, as it plays a critical role in maintaining intracellular amino acid levels and supporting proliferation.
Article
Oncology
Marco H. Hofmann, Michael Gmachl, Juergen Ramharter, Fabio Savarese, Daniel Gerlach, Joseph R. Marszalek, Michael P. Sanderson, Dirk Kessler, Francesca Trapani, Heribert Arnhof, Klaus Rumpel, Dana-Adriana Botesteanu, Peter Ettmayer, Thomas Gerstberger, Christiane Kofink, Tobias Wunberg, Andreas Zoephel, Szu-Chin Fu, Jessica L. Teh, Jark Boettcher, Nikolai Pototschnig, Franziska Schachinger, Katharina Schipany, Simone Lieb, Christopher P. Vellano, Jonathan C. O'Connell, Rachel L. Mendes, Jurgen Moll, Mark Petronczki, Timothy P. Heffernan, Mark Pearson, Darryl B. McConnell, Norbert Kraut
Summary: Inhibiting SOS1, a KRAS activator and important feedback node, is an effective approach to treat KRAS-driven cancers. The highly potent and selective small-molecule SOS1 inhibitor, BI-3406, reduces cellular proliferation of KRAS-driven cancers by preventing the interaction with KRAS. Combination of SOS1 and MEK inhibition represents a novel and effective therapeutic concept for addressing KRAS-driven tumors.
Article
Oncology
Dominic Esposito, Andrew G. Stephen, Thomas J. Turbyville, Matthew Holderfield
SEMINARS IN CANCER BIOLOGY
(2019)
Article
Oncology
G. Aaron Hobbs, Nicole M. Baker, Anne M. Miermont, Ryan D. Thurman, Mariaelena Pierobon, Timothy H. Tran, Andrew O. Anderson, Andrew M. Waters, J. Nathaniel Diehl, Bjoern Papke, Richard G. Hodge, Jennifer E. Klomp, Craig M. Goodwin, Jonathan M. DeLiberty, Junning Wang, Raymond W. S. Ng, Prson Gautam, Kirsten L. Bryant, Dominic Esposito, Sharon L. Campbell, Emanuel F. Petricoin, Dhirendra K. Simanshu, Andrew J. Aguirre, Brian M. Wolpin, Krister Wennerberg, Udo Rudloff, Adrienne D. Cox, Channing J. Der
Letter
Multidisciplinary Sciences
Timothy H. Tran, Patrick Alexander, Srisathiyanarayanan Dharmaiah, Constance Agamasu, Dwight V. Nissley, Frank McCormick, Dominic Esposito, Dhirendra K. Simanshu, Andrew G. Stephen, Trent E. Balius
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Que N. Van, Cesar A. Lopez, Marco Tonelli, Troy Taylor, Ben Niu, Christopher B. Stanley, Debsindhu Bhowmik, Timothy H. Tran, Peter H. Frank, Simon Messing, Patrick Alexander, Daniel Scott, Xiaoying Ye, Matt Drew, Oleg Chertov, Mathias Losche, Arvind Ramanathan, Michael L. Gross, Nicolas W. Hengartner, William M. Westler, John L. Markley, Dhirendra K. Simanshu, Dwight Nissley, William K. Gillette, Dominic Esposito, Frank McCormick, S. Gnanakaran, Frank Heinrich, Andrew G. Stephen
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Timothy H. Tran, Albert H. Chan, Lucy C. Young, Lakshman Bindu, Chris Neale, Simon Messing, Srisathiyanarayanan Dharmaiah, Troy Taylor, John-Paul Denson, Dominic Esposito, Dwight V. Nissley, Andrew G. Stephen, Frank McCormick, Dhirendra K. Simanshu
Summary: This study presents molecular details of the RAS-RAF interaction, including the crystal structures of KRAS binding with RAF1 and a proposed model of membrane-bound RAS-RAF complex formation.
NATURE COMMUNICATIONS
(2021)
Article
Biophysics
Frank Heinrich, Que N. Van, Frantz Jean-Francois, Andrew G. Stephen, Mathias Loesche
Summary: Research findings show that KRAS4B approximates an entropic ensemble of configurations in specific membrane environments, with interactions between the protein and lipid membrane having minimal impact on its shape. This challenges previous understanding of KRAS signaling and proposes a new model where the protein samples in a uniform manner and binds to effector proteins.
BIOPHYSICAL JOURNAL
(2021)
Article
Oncology
David E. Durrant, Emily A. Smith, Ekaterina Goncharova, Nirmala Sharma, Patrick A. Alexander, Andrew G. Stephen, Curtis J. Henrich, Deborah K. Morrison
Summary: This study utilized a NanoBRET screening platform to identify compounds that inhibit the binding between activated KRAS and CRAF kinase, leading to suppression of RAS-driven ERK activation. However, some compounds were found to enhance the interaction and upregulate pathway signaling.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Multidisciplinary Sciences
Helgi I. Ingolfsson, Chris Neale, Timothy S. Carpenter, Rebika Shrestha, Cesar A. Lopez, Timothy H. Tran, Tomas Oppelstrup, Harsh Bhatia, Liam G. Stanton, Xiaohua Zhang, Shiv Sundram, Francesco Di Natale, Animesh Agarwal, Gautham Dharuman, Sara I. L. Kokkila Schumacher, Thomas Turbyville, Gulcin Gulten, Que N. Van, Debanjan Goswami, Frantz Jean-Francois, Constance Agamasu, De Chen, Jeevapani J. Hettige, Timothy Travers, Sumantra Sarkar, Michael P. Surh, Yue Yang, Adam Moody, Shusen Liu, Brian C. Van Essen, Arthur F. Voter, Arvind Ramanathan, Nicolas W. Hengartner, Dhirendra K. Simanshu, Andrew G. Stephen, Peer-Timo Bremer, S. Gnanakaran, James N. Glosli, Felice C. Lightstone, Frank McCormick, Dwight Nissley, Frederick H. Streitz
Summary: In this study, a scale-bridging ensemble of over 100,000 simulations of RAS-membrane interactions was created using machine learning. The simulations revealed distinctive patterns of lipid composition that are correlated with RAS dynamics, potentially providing a mechanism for regulating cell signaling cascades.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Physical
Cesar A. Lopez, Xiaohua Zhang, Fikret Aydin, Rebika Shrestha, Que N. Van, Christopher B. Stanley, Timothy S. Carpenter, Kien Nguyen, Lara A. Patel, De Chen, Violetta Burns, Nicolas W. Hengartner, Tyler J. E. Reddy, Harsh Bhatia, Francesco Di Natale, Timothy H. Tran, Albert H. Chan, Dhirendra K. Simanshu, Dwight V. Nissley, Frederick H. Streitz, Andrew G. Stephen, Thomas J. Turbyville, Felice C. Lightstone, Sandrasegaram Gnanakaran, Helgi I. Ingolfsson, Chris Neale
Summary: The appeal of multiscale modeling approaches lies in the promise of utilizing the synergistic effects between different scales. This paper focuses on multiscale molecular dynamics simulations that combine accuracy and flexibility of fixed-charge all-atom representations with the speed of reductive, coarse-grained representations. The authors introduce an extension to the MuMMI framework and an improved CG-to-AA conversion tool called sinceCG, providing reliable and robust scale conversion.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Immunology
Qianqian Ming, Daiana P. Celias, Chao Wu, Aidan R. Cole, Srishti Singh, Charlotte Mason, Shen Dong, Timothy H. Tran, Gaya K. Amarasinghe, Brian Ruffell, Vincent C. Luca
Summary: The authors provide the crystal structure of human and mouse LAG3 ectodomains, showing how they interact with known ligands and antibodies. The insights gained from this study are important for LAG3-based drug development and understanding the mechanism of disrupting T cell activation.
Article
Oncology
Marine Potez, Sebastian Snedal, Chunhua She, Jongmyung Kim, Konrad Thorner, Timothy H. H. Tran, Maria Cecilia Ramello, Daniel Abate-Daga, James K. C. Liu
Summary: Researchers have identified 7-amino acid peptides that specifically target glioma stem cells (GSCs) through in vitro and in vivo phage display biopanning. They created a dual peptide construct and demonstrated its ability to bind GSCs in vitro and target intracranial GBM in mouse models. They also engineered chimeric antigen receptor (CAR)-transduced T cells that specifically react and induce apoptosis in GSCs.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biology
Fa-An Chao, Albert H. Chan, Srisathiyanarayanan Dharmaiah, Charles D. Schwieters, Timothy H. Tran, Troy Taylor, Nitya Ramakrishnan, Dominic Esposito, Dwight V. Nissley, Frank McCormick, Dhirendra K. Simanshu, Gabriel Cornilescu
Summary: Structural analysis of GMPPNP-bound KRAS(G13D) reveals an intermediate state with a new pocket, providing an opportunity for developing targeted therapies against KRAS(G13D)-driven cancers. Dynamics of RAS, including distal regions, is important for understanding its interactions with effectors and designing inhibitors. Methyl relaxation dispersion experiments show synchronized conformational dynamics in active KRAS(G13D), suggesting an exchange between two states. Residual dipolar couplings and crystal structures confirm the presence of an intermediate state distinct from known conformations.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shweta Shree, Mark A. McLean, Andrew G. Stephen, Stephen G. Sligar
Summary: KRas4b is a membrane-bound regulatory protein involved in signal transduction and cell growth, and its conformation is influenced by anionic lipids.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
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.