Journal ArticleDOI
RNA viruses and the mitogenic Raf/MEK/ERK signal transduction cascade.
TLDR
The Raf/MEK/ERK signal transduction cascade belongs to the mitogen-activated protein kinase (MAPK) cascades, and is induced by extracellular agents, including pathogens such as RNA viruses, to induce cellular signaling via this pathway.Abstract:
The Raf/MEK/ERK signal transduction cascade belongs to the mitogen-activated protein kinase (MAPK) cascades. Raf/MEK/ERK signaling leads to stimulus-specific changes in gene expression, alterations in cell metabolism or induction of programmed cell death (apoptosis), and thus controls cell differentiation and proliferation. It is induced by extracellular agents, including pathogens such as RNA viruses. Many DNA viruses are known to induce cellular signaling via this pathway. As these pathogens partly use the DNA synthesis machinery for their replication, they aim to drive cells into a proliferative state. In contrast, the consequences of RNA virus-induced Raf/MEK/ERK signaling were less clear for a long time, but since the turn of the century the number of publications on this topic has rapidly increased. Research on this virus/host-interaction will broaden our understanding of its relevance in viral replication. This important control center of cellular responses is differently employed to support the replication of several important human pathogenic RNA viruses including influenza, Ebola, hepatitis C and SARS corona viruses.read more
Citations
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Journal ArticleDOI
Antiviral Potential of ERK/MAPK and PI3K/AKT/mTOR Signaling Modulation for Middle East Respiratory Syndrome Coronavirus Infection as Identified by Temporal Kinome Analysis
Jason Kindrachuk,Britini L. Ork,Brit J. Hart,Steven Mazur,Michael R. Holbrook,Matthew B. Frieman,Dawn Traynor,Reed F. Johnson,Julie Dyall,Jens H. Kuhn,Gene G. Olinger,Lisa E. Hensley,Peter B. Jahrling +12 more
TL;DR: In this paper, the authors performed temporal kinome analysis on human hepatocytes infected with the Erasmus isolate of MERS-CoV with peptide kinome arrays and found that ERK/MAPK and PI3K/AKT/mTOR signaling responses were specifically modulated in response to infection in vitro throughout the course of infection.
Journal ArticleDOI
Cellular and molecular mechanisms of hepatocellular carcinoma: an update.
TL;DR: The current knowledge of HCC is discussed, focusing mainly on advances that have occurred during the past 5 years and on the development of novel therapeutics for liver cancer.
Journal ArticleDOI
Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication
Julianna Han,Jasmine T. Perez,Cindy Chen,Yan Li,Asiel Arturo Benitez,Matheswaran Kandasamy,Yoontae Lee,Jorge Andrade,Benjamin R. tenOever,Balaji Manicassamy +9 more
TL;DR: This study demonstrates that the CRISPR/Cas9 system can be utilized for the discovery of host factors critical for the replication of intracellular pathogens and has identified capicua (CIC) as a negative regulator of cell-intrinsic immunity.
Journal ArticleDOI
Inhibition of influenza virus-induced NF-kappaB and Raf/MEK/ERK activation can reduce both virus titers and cytokine expression simultaneously in vitro and in vivo.
Ruth Pinto,Susanne Herold,Lidija Cakarova,Katrin Hoegner,Jürgen Lohmeyer,Oliver Planz,Stephan Pleschka +6 more
TL;DR: It is demonstrated for the first time in vitro and in vivo that virus titers and pro-inflammatory cytokine expression can be modulated simultaneously and could provide a new rationale of future therapeutic strategies to treat IV pneumonia.
Journal ArticleDOI
Influenza viruses and the NF-kappaB signaling pathway - towards a novel concept of antiviral therapy
Stephan Ludwig,Oliver Planz +1 more
TL;DR: New insights are provided into the pathophysiological function of NF-κB in the special environment of a virus-infected cell and the unexpected viral dependency on a cellular signaling factor may pave the path for novel antiviral approaches targeting essential cellular components rather than viral factors.
References
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Journal ArticleDOI
Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions.
Gray W. Pearson,Fred L. Robinson,Tara Beers Gibson,Bing E. Xu,Mahesh Karandikar,Kevin S. Berman,Melanie H. Cobb +6 more
TL;DR: Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted and particular emphasis is on ERK1/2.
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Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.
TL;DR: The current status of the different approaches and targets that are under evaluation and development for the therapeutic intervention of this key signaling pathway in human disease are summarized.
Journal ArticleDOI
Protein kinases--the major drug targets of the twenty-first century?
TL;DR: A personal view of some of the most important advances that have shaped this field of protein kinases, after G-protein-coupled receptors.
Journal ArticleDOI
Lipid signalling in disease
TL;DR: A more integrated overview of the key role of these signalling lipids in inflammation, cancer and metabolic disease is attempted, and emerging strategies for therapeutic intervention are discussed.
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Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo.
Judith Sebolt-Leopold,David T. Dudley,Roman Herrera,K Van Becelaere,A Wiland,Richard C. Gowan,Haile Tecle,Stephen Douglas Barrett,Alexander James Bridges,Sally A. Przybranowski,Wilbur R. Leopold,Alan R. Saltiel +11 more
TL;DR: The discovery of a highly potent and selective inhibitor of the upstream kinase MEK that is orally active is reported, indicating that MEK inhibitors represent a promising, noncytotoxic approach to the clinical management of colon cancer.