Article
Cell Biology
Xu Chen, Zheng-Qian Guo, Dan Cao, Yong Chen, Jian Chen
Summary: The study revealed that overexpression of PNO1 in glioma is associated with poor prognosis, and that PNO1 contributes to glioma progression by activating THBS1/FAK/Akt signaling pathway.
CELL DEATH & DISEASE
(2021)
Article
Endocrinology & Metabolism
Takahiro Mori, Satoru Ato, Jonas R. Knudsen, Carlos Henriquez-Olguin, Zhencheng Li, Koki Wakabayashi, Takeshi Suginohara, Kazuhiko Higashida, Yuki Tamura, Koichi Nakazato, Thomas E. Jensen, Riki Ogasawara
Summary: The study found that c-Myc overexpression is sufficient to stimulate skeletal muscle ribosome biogenesis and protein synthesis without activation of mTORC1. This may provide new insights into the mechanisms of ribosome biogenesis and protein synthesis following high-intensity muscle contractions.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Engineering, Aerospace
Sergey Rozhkov, Kristina A. Sharlo, Timur M. Mirzoev, Boris S. Shenkman
Summary: The study found that during hindlimb unloading in rat soleus muscle, the expression of regulators/markers of ribosome biogenesis significantly decreased during inactivity, which was accompanied by a progressive decrease in MPS. This suggests that ribosome synthesis plays a crucial role in skeletal muscle inactivity.
Article
Pharmacology & Pharmacy
Wang-Jing Zhong, Lingdi Ma, Fanfan Yang, Jialin Cao, Junyu Tan, Bohong Li
Summary: Matrine, a natural compound from Sophora flavescens, inhibits c-Myc, suppresses ribosome biogenesis and nucleotide metabolism, and shows potential for developing derivatives to target c-Myc-driven cancers.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Julia S. P. Mawer, Jennifer Massen, Christina Reichert, Niklas Grabenhorst, Constantine Mylonas, Peter Tessarz
Summary: Ribosome biogenesis is a complex cellular process that involves integration of extracellular cues, such as metabolic state and intracellular signaling, transcriptional regulation, and chromatin accessibility at the ribosomal DNA. The recently identified histone modification, methylation of H2AQ105 (H2AQ105me), plays a key role in this process, dependent on the mTor signaling pathway and acetylation of histone H3. The ribonucleoprotein Nhp2 acts as an epigenetic reader of this modification, bridging rDNA chromatin with components of the small subunit processome to coordinate transcription of rRNA with its post-transcriptional processing.
Article
Biochemistry & Molecular Biology
Sergey V. Rozhkov, Kristina A. Sharlo, Boris S. Shenkman, Timur M. Mirzoev
Summary: It has been established that prolonged exposure to microgravity/disuse conditions can lead to a decrease in muscle protein synthesis and muscle mass. This study investigated the effects of inhibiting GSK-3 activity on the downregulation of ribosome biogenesis and muscle protein synthesis in rat soleus muscle during hindlimb suspension. The results showed that inhibition of GSK-3 partially attenuated the reductions in translational capacity and muscle protein synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Ho Tsoi, Chan-Ping You, Man-Hong Leung, Ellen P. S. Man, Ui-Soon Khoo
Summary: Breast cancer is a heterogeneous disease, and most cases are estrogen receptor-positive. However, many patients eventually develop resistance to the main treatment drug tamoxifen. Overexpression of c-MYC can drive the development of estrogen receptor-positive breast cancer and confer tamoxifen resistance. Ribosome biogenesis plays a crucial role in this process, and suppressing ribosome biogenesis may help reduce aggressiveness and reverse tamoxifen resistance. Some chemicals have been shown to repress ribosome biogenesis and may potentially reverse tamoxifen resistance in estrogen receptor-positive breast cancer. Identification of predictive markers will be necessary for the future use of these ribosome biogenesis inhibitors in combating tamoxifen resistance.
Article
Cell Biology
Isabella N. Brown, M. Carmen Lafita-Navarro, Maralice Conacci-Sorrell
Summary: The nucleolus plays a crucial role in protein synthesis by producing new ribosomes. In cancer, nucleolar activity is heightened due to increased demand for protein synthesis. The transcription factor MYC promotes nucleolar activity and understanding and potentially inhibiting aberrant nucleolar activity in cancer cells could lead to novel therapeutics.
Article
Hematology
Ava Keyvani Chahi, Muluken S. Belew, Joshua Xu, He Tian Tony Chen, Stefan Rentas, Veronique Voisin, Gabriela Krivdova, Eric Lechman, Sajid A. Marhon, Daniel D. De Carvalho, John E. Dick, Gary D. Bader, Kristin J. Hope
Summary: This study identifies the transcription factor PLAG1 as a key regulator of hematopoietic stem cell (HSC) dormancy and self-renewal. PLAG1 dampens protein synthesis, restrains cell growth and division, and enhances survival, promoting the frequency of functional HSCs. It utilizes multiple regulatory factors to ensure protective diminished protein synthesis. Regulated translation control underlying human HSC physiology is important and its dysregulation may have therapeutic potential.
Article
Biochemistry & Molecular Biology
Mitsuru Okuwaki, Shoko Saito, Hiroko Hirawake-Mogi, Kyosuke Nagata
Summary: This study revealed that the nucleolar localization of NPM1 and the large ribosomal subunit precursors are mutually dependent. NPM1 plays a crucial role in maintaining the structure of large ribosomal subunits and the accumulation of late processing machinery in the nucleolus.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Leonid Anikin, Dimitri G. Pestov
Summary: Aminoacridines, historically used as antiseptic and antiparasitic agents, could be repurposed for therapeutic use and new drug development. In this study, the effects of 9-aminoacridine on pre-rRNA metabolism in mammalian cells were investigated. The results showed that 9-aminoacridine inhibits both pre-rRNA transcription and processing, leading to the disruption of ribosome biogenesis. The ability of 9-aminoacridine to bind to RNA in vitro suggests its potential as a new ribosome biogenesis inhibitor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Sohail Khoshnevis, R. Elizabeth Dreggors-Walker, Virginie Marchand, Yuri Motorin, Homa Ghalei
Summary: Protein synthesis by ribosomes is crucial for gene expression in cells, and 2'-O-methylation is a common modification on ribosomal RNAs. This study reveals that changes in the biogenesis of snoRNPs, which guide 2'-O-methylation, lead to the production of ribosomes with distinct translational properties. The hypo-2'-O-methylated ribosomes show translational defects and affect ribosome dynamics and ligand binding. This highlights the importance of 2'-O-methylation in regulating cellular translation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Zhiyong Liu, Yanan Pang, Yin Jia, Qin Qin, Rui Wang, Wei Li, Jie Jing, Haidong Liu, Shanrong Liu
Summary: This study found that SNORA23 regulates ribosome biogenesis in hepatocellular carcinoma (HCC) by impairing the 2'-O-ribose methylation of 28S rRNA. SNORA23 inhibits the proliferation, migration, and invasion of HCC cells in vitro and in vivo. It is regulated by the PI3K/Akt/mTOR signaling pathway and inhibits the phosphorylation of 4E binding protein 1.
CANCER BIOLOGY & MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Pallavi Mohapatra, Sibasish Mohanty, Shamima Azma Ansari, Omprakash Shriwas, Arup Ghosh, Rachna Rath, Saroj Kumar Das Majumdar, Rajeeb K. Swain, Sunil K. Raghav, Rupesh Dash
Summary: CMTM6 is a major driver of cisplatin resistance in oral squamous cell carcinomas. The study explores the detailed mechanism of how CMTM6 rewires cisplatin resistance by regulating the ribosome biogenesis network.
Article
Biochemistry & Molecular Biology
Cherry Yin-Yi Chang, An-Jen Chiang, Man-Ju Yan, Ming-Tsung Lai, Yun-Yi Su, Hsin-Yi Huang, Chan-Yu Chang, Ya-Hui Li, Pei-Fen Li, Chih-Mei Chen, Tritium Hwang, Chloe Hogg, Erin Greaves, Jim Jinn-Chyuan Sheu
Summary: Ribosome biogenesis is up-regulated during endometriosis progression and malignant transition, and blocking this process can reduce lesion numbers and disease frequencies, suppress inflammation, and provide pain relief.
Article
Oncology
Lisa C. Wellinger, Simon J. Hogg, Dane M. Newman, Thomas Friess, Daniela Geiss, Jessica Michie, Kelly M. Ramsbottom, Marina Bacac, Tanja Fauti, Daniel Marbach, Laura Jarassier, Phillip Thienger, Axel Paehler, Leonie A. Cluse, Conor J. Kearney, Stephin J. Vervoort, Joseph A. Trapani, Jane Oliaro, Jake Shortt, Astrid Ruefli-Brasse, Daniel Rohle, Ricky W. Johnstone
Summary: Targeting chromatin binding proteins and modifying enzymes can enhance antitumor immunity and effectiveness of cancer immunotherapies by affecting tumor cell proliferation and survival. BET inhibitors sensitize tumor cells to TNF-induced cell death and suppress inflammatory gene expression, leading to enhanced tumor growth inhibition in combination with T-cell bispecific antibodies or immune-checkpoint blockade.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Multidisciplinary Sciences
Lorey K. Smith, Tiffany Parmenter, Margarete Kleinschmidt, Eric P. Kusnadi, Jian Kang, Claire A. Martin, Peter Lau, Riyaben Patel, Julie Lorent, David Papadopoli, Anna Trigos, Teresa Ward, Aparna D. Rao, Emily J. Lelliott, Karen E. Sheppard, David Goode, Rodney J. Hicks, Tony Tiganis, Kaylene J. Simpson, Ola Larsson, Benjamin Blythe, Carleen Cullinane, Vihandha O. Wickramasinghe, Richard B. Pearson, Grant A. McArthur
Summary: This study investigates the impact of BRAF inhibition on metabolism in melanoma cells. Through a genome-wide RNA interference screen and gene expression profiling, the researchers found that BRAF inhibition can regulate metabolism through selective mRNA transport and translation. They discovered that U2AF homology motif kinase 1 (UHMK1) associates with mRNAs encoding metabolism proteins and controls their transport and translation during adaptation to BRAF-targeted therapy. Inactivation of UHMK1 leads to cell death and delays resistance to BRAF and MEK combination therapy.
NATURE COMMUNICATIONS
(2022)
Article
Medical Informatics
Mollie Hobensack, Deborah R. Levy, Kenrick Cato, Don E. Detmer, Kevin B. Johnson, Jeffrey Williamson, Judy Murphy, Amanda Moy, Jennifer Withall, Rachel Lee, Sarah Collins Rossetti, Samuel Trent Rosenbloom
Summary: The high documentation requirements among United States clinicians have resulted in clinician burnout and suboptimal patient care. The 25 by 5 Symposium aimed to reduce documentation burden by providing a platform for experts to discuss the issue and identify specific actions. The symposium produced a list of interventions for short-, medium-, and long-term goals, with themes including accountability, evidence, education and training, and technology innovation.
APPLIED CLINICAL INFORMATICS
(2022)
Article
Pharmacology & Pharmacy
Gregory Gauthier-Coles, Angelika Broer, Malcolm Donald McLeod, Amee J. George, Ross D. Hannan, Stefan Broer
Summary: SNAT2 is an important amino acid transporter involved in amino acid accumulation, cellular osmolarity, and cell growth. A potent inhibitor of SNAT2 has been identified through high-throughput screening, with selectivity against other transporters. Combined with a glucose transport inhibitor, this compound can halt the proliferative growth of cancer cells.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Irina C. Frei, Diana Weissenberger, Danilo Ritz, Wolf Heusermann, Marco Colombi, Mitsugu Shimobayashi, Michael N. Hall
Summary: This study identifies a network of sensory neurons in murine white adipose tissue and reveals the involvement of adipose mTORC2 in the development and maintenance of these neurons. The loss of sensory innervation in adipose tissue is found to coincide with systemic insulin resistance, suggesting a potential role of sensory neurons in whole-body energy homeostasis.
MOLECULAR METABOLISM
(2022)
Article
Developmental Biology
Olga Zaytseva, Naomi C. Mitchell, Damien Muckle, Caroline Delandre, Zuqin Nie, Janis K. Werner, John T. Lis, Eduardo Eyras, Ross D. Hannan, David L. Levens, Owen J. Marshall, Leonie M. Quinn
Summary: FUBP1 and Psi, members of the FUSE Binding Protein family, regulate gene transcription by binding to single-stranded DNA and RNA, promoting cell growth and division. Psi activates Myc and stg to promote cell proliferation, while repressing the transcription of tok, a growth inhibitor.
Article
Biochemistry & Molecular Biology
Sunil Shetty, Jon Hofstetter, Stefania Battaglioni, Danilo Ritz, Michael N. Hall
Summary: Target of rapamycin complex 1 (TORC1) promotes ribosome biogenesis and inhibits degradation in response to nutrient availability. The dormant 80S ribosomes formed under nutrient-limited conditions are regulated by the ribosome preservation factor Stm1, which is inhibited by TORC1 upon nutrient replenishment to reactivate translation. Furthermore, the mammalian ortholog of Stm1, SERBP1, is also required for the formation of dormant ribosomes in mammalian cells upon mTORC1 inhibition, suggesting an evolutionarily conserved mechanism for ribosomal dormancy regulation.
Article
Oncology
Victoria Y. Ling, Jasmin Straube, William Godfrey, Rohit Haldar, Yashaswini Janardhanan, Leanne Cooper, Claudia Bruedigam, Emily Cooper, Paniz Tavakoli Shirazi, Sebastien Jacquelin, Siok-Keen Tey, Jonathan Baell, Fei Huang, Jianwen Jin, Yichao Zhao, Lars Bullinger, Megan J. Bywater, Steven W. Lane
Summary: This study identifies defective cell cycle arrest as a clinically relevant contributor to chemoresistance in acute myeloid leukemia (AML). Downregulation of CDKN2A is associated with inferior overall survival in AML patients and occurs at relapse. Therapeutic targeting of the G(1)S cell cycle restriction point and promotion of apoptosis can enhance chemotherapy response in AML.
Article
Oncology
Jasmin Straube, Theresa Eifert, Therese Vu, Yashaswini Janardhanan, Rohit Haldar, Bjoern von Eyss, Leanne Cooper, Claudia Bruedigam, Victoria Y. Ling, Emily Cooper, Ann-Marie Patch, Lars Bullinger, Tina M. Schnoeder, Megan Bywater, Florian H. Heidel, Steven W. Lane
Summary: Murine models are useful for studying AML subtypes and compound mutations. The Cre recombinase expression in a transgenic murine model can lead to aggressive leukemia phenotype, polyclonal expansion of FLT3(ITD/ITD) progenitor cells, differentiation block and activation of Myc-dependent gene expression programs. Our report highlights the potential risks and unexpected effects of Cre expression in investigating oncogenic mutations in murine cancer models.
Article
Endocrinology & Metabolism
Irina C. Frei, Diana Weissenberger, Michael N. Hall, Mitsugu Shimobayashi
Summary: Mammalian target of rapamycin complex 2 (mTORC2) is a protein kinase complex that plays an important role in energy homeostasis. Loss of adipose mTORC2 reduces lipogenic enzyme expression and de novo lipogenesis in adipose tissue. Adipose-specific mTORC2 knockout mice also display triglyceride accumulation in the liver.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Biodiversity Conservation
Rachel S. K. Lee, Calebe P. P. Mendes, Stacey S. Q. Liang, Vera W. X. Yang, Delaney K. L. Eng, Wei Bin Ong, Yen Kheng Chua, Greg Byrnes, Norman T. -L. Lim
Summary: Researchers developed a vector-based model and applied a genetic algorithm to determine optimal glide pole locations, improving connectivity for arboreal gliding mammals and mitigating negative impacts of road widening. By using the model, the number of installed glide poles increased by 10 times and filled connectivity gaps created by road widening. This model fills a knowledge gap in connectivity modelling for arboreal gliding mammals and is important for their conservation efforts.
JOURNAL OF APPLIED ECOLOGY
(2023)
Article
Multidisciplinary Sciences
Rebecca J. Austin, Jasmin Straube, Rohit Halder, Yashaswini Janardhanan, Claudia Bruedigam, Matthew Witkowski, Leanne Cooper, Amy Porter, Matthias Braun, Fernando Souza-Fonseca-Guimaraes, Simone A. Minnie, Emily Cooper, Sebastien Jacquelin, Axia Song, Tobias Bald, Kyohei Nakamura, Geoffrey R. Hill, Iannis Aifantis, Steven W. Lane, Megan J. Bywater
Summary: AML is a genetically heterogeneous and aggressive hematological malignancy caused by distinct oncogenic driver mutations. The impact of specific AML oncogenes on immune response remains uncertain. This study reveals that different AML oncogenes determine immunogenicity, quality of immune response, and immune escape through immunoediting. The findings emphasize the significance of personalized immunotherapies for AML patients.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Mitsugu Shimobayashi, Amandine Thomas, Sunil Shetty, Irina C. Frei, Bettina K. Wolnerhanssen, Diana Weissenberger, Anke Vandekeere, Melanie Planque, Nikolaus Dietz, Danilo Ritz, Anne Christin Meyer-Gerspach, Timm Maier, Nissim Hay, Ralph Peterli, Sarah-Maria Fendt, Nicolas Rohner, Michael N. Hall
Summary: Chronically high blood glucose leads to diabetes and fatty liver disease. Obesity is a major risk factor for hyperglycemia, but the underlying mechanism is unknown. This study shows that a high-fat diet causes early loss of expression of the glycolytic enzyme Hexokinase 2 specifically in adipose tissue, leading to reduced glucose disposal and lipogenesis and enhanced fatty acid release. Furthermore, the study identifies adipose HK2 as a critical mediator of glucose homeostasis and suggests that obesity-induced loss of adipose HK2 is an evolutionarily conserved mechanism for the development of selective insulin resistance and hyperglycemia.
Article
Biochemistry & Molecular Biology
Dirk Mossmann, Christoph Mueller, Sujin Park, Brendan Ryback, Marco Colombi, Nathalie Ritter, Diana Weissenberger, Eva Dazert, Mairene Coto-Llerena, Sandro Nuciforo, Lauriane Blukacz, Caner Ercan, Veronica Jimenez, Salvatore Piscuoglio, Fatima Bosch, Luigi M. Terracciano, Uwe Sauer, Markus H. Heim, Michael N. Hall
Summary: Metabolic reprogramming is a hallmark of cancer, and arginine is identified as a second messenger-like molecule that promotes tumor growth by controlling the expression of metabolic genes.
Article
Multidisciplinary Sciences
Maurizio Cortada, Soledad Levano, Michael N. Hall, Daniel Bodmer
Summary: The mTORC2 signaling pathway plays a crucial role in regulating auditory hair cell (HC) structure and function through the regulation of the actin cytoskeleton. This study provides molecular insights into the central regulator of cochlear HCs and hearing.