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MAPK Signaling Cascades in Human Health and Diseases 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 526

Special Issue Editor


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Guest Editor
Department of Immunology & Regenerative Biology, Weizmann Institute of Science, Rehovot 7610001, Israel
Interests: signal transduction; signaling protein kinases; cancer signalings; kinase cascades

Special Issue Information

Dear Colleagues,

Mitogen-activated protein kinase (MAPK) cascades are a group of signaling pathways that regulate a multitude of intracellular processes, including metabolism, proliferation, differentiation, motility, apoptosis, and cell-specific functions. For this purpose, the cascades induce a stimulated phosphorylation of hundreds of substrates that are localized in various cellular compartments, particularly the cytoplasm in resting cells and the nucleus upon stimulation. Importantly, dysregulation of the cascades leads to various diseases, including cancer, inflammation, and developmental disorders. Therefore, MAPK cascades are recognized as important drug targets for treating all these pathologies. In this Special Issue, we aim to highlight the role and mode of regulation of the MAPK cascades, with a special emphasis on their nuclear activities.

As the Guest Editor, I am pleased to announce the opening for submission to this Special Issue entitled “MAPK Signaling Cascades in Human Health and Diseases 2.0”. This Special Issue is open to both original research articles and review articles.

I look forward to your response regarding your contribution to this Special Issue.

Dr. Galia Maik-Rachline
Guest Editor

Manuscript Submission Information

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Keywords

  • ERK1/2
  • p38
  • JNK
  • ERK5
  • MEK
  • MEKK
  • raf
  • stimulated nuclear translocation
  • targeted therapy
  • resistance mechanisms

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Published Papers (1 paper)

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Research

18 pages, 1514 KiB  
Article
Probenecid Inhibits Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase Mitogen-Activated Protein Kinase Pathways in Regulating Respiratory Syncytial Virus Response
by Les P. Jones, Harrison C. Bergeron, David E. Martin, Jackelyn Murray, Fred D. Sancilio and Ralph A. Tripp
Int. J. Mol. Sci. 2024, 25(22), 12452; https://doi.org/10.3390/ijms252212452 - 20 Nov 2024
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Abstract
We examined the effect of probenecid in regulating the ERK and JNK downstream MAPK pathways affecting respiratory syncytial virus replication. Background: We have previously shown that probenecid inhibits RSV, influenza virus, and SARS-CoV-2 replication in vitro in preclinical animal models and in humans. [...] Read more.
We examined the effect of probenecid in regulating the ERK and JNK downstream MAPK pathways affecting respiratory syncytial virus replication. Background: We have previously shown that probenecid inhibits RSV, influenza virus, and SARS-CoV-2 replication in vitro in preclinical animal models and in humans. In a Phase two randomized, placebo-controlled, single-blind, dose range-finding study using probenecid to treat non-hospitalized patients with symptomatic, mild-to-moderate COVID-19, we previously showed that a 1000 mg twice daily treatment for 5 days reduced the median time to viral clearance from 11 to 7 days, and a 500 mg twice daily treatment for 5 days reduced the time to viral clearance from 11 to 9 days more than the placebo. Methods: In this study, we sought to determine the mechanism of action of the probenecid inhibition of RSV replication in human respiratory epithelial (A549) cells. Results: We show that probenecid inhibits the RSV-induced phosphorylation of JNKs and ERKs and the downstream phosphorylation of c-jun, a component of the AP-1 transcription complex needed for virus replication. The inhibition of JNKs by probenecid reversed the repression of transcription factor HNF-4. Conclusion: The probenecid inhibition of JNK and ERK phosphorylation involves the MAPK pathway that precludes virus replication. Full article
(This article belongs to the Special Issue MAPK Signaling Cascades in Human Health and Diseases 2.0)
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