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Special Issue "MAPK-ERK Pathway"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 31 December 2019.

Special Issue Editor

Guest Editor
Prof. Dr. Jong-In Park

Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Website | E-Mail
Interests: Mechanisms of MEK/ERK growth arrest signaling

Special Issue Information

Dear Colleagues,

The Raf/MEK/Extracellular signal-regulated kinase (ERK/MAPK) pathway is a highly specific three-layered kinase cascade that has pivotal roles in a variety of cellular processes, including cell cycle progression, survival, and differentiation. The deregulation of this pathway is implicated in a variety of pathophysiological conditions, including cancers, metabolic diseases, neurological disorders, and genetically inherited disorders. The kinase cascade of this pathway consists of the Ser/Thr kinases, A-Raf, B-Raf, and C-Raf-1, the highly homologous dual-specificity kinases, MEK1 and MEK2, and the ubiquitously expressed serine/threonine kinase, ERK1 and ERK2 (collectively referred to as ERK1/2). As the key focal point of pathway signaling, ERK1/2 activate/inactivate a variety of targets, including transcription factors, other kinases, phosphatases, cytoskeletal proteins, scaffolds, receptors, and signaling components. The specificity of pathway signaling is determined at multiple levels, including regulation of the magnitude and duration of pathway activity, spatio-temporal regulation, regulation of the monomeric vs. dimeric status of ERK1/2, as well as its crosstalk with other pathways. Recent studies have substantially expanded our knowledge of the pathway signaling at molecular levels, allowing the development of diverse potential therapeutic strategies targeting this pathway.

This Special Issue covers recent advances in the molecular mechanisms and biological functions of the ERK/MAPK pathway signaling, its regulators and downstream effectors, as well as the relevance of these aspects in human disease and potential therapeutic strategies. We encourage authors to submit original research articles or reviews.

Prof. Dr. Jong-In Park
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ERK/MAPK signaling in cell survival, proliferation, and differentiation
  • aberrant ERK/MAPK signaling in disease
  • regulators of the ERK/MAPK pathway
  • downstream effectors of the ERK/MAPK pathway
  • targeting the ERK/MAPK pathway in diseases
  • drug resistance to the ERK/MAPK pathway inhibition

Published Papers (4 papers)

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Research

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Open AccessArticle
Activin B Stimulates Mouse Vibrissae Growth and Regulates Cell Proliferation and Cell Cycle Progression of Hair Matrix Cells through ERK Signaling
Int. J. Mol. Sci. 2019, 20(4), 853; https://doi.org/10.3390/ijms20040853
Received: 24 December 2018 / Revised: 5 February 2019 / Accepted: 9 February 2019 / Published: 15 February 2019
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Abstract
Activins and their receptors play important roles in the control of hair follicle morphogenesis, but their role in vibrissae follicle growth remains unclear. To investigate the effect of Activin B on vibrissae follicles, the anagen induction assay and an in vitro vibrissae culture [...] Read more.
Activins and their receptors play important roles in the control of hair follicle morphogenesis, but their role in vibrissae follicle growth remains unclear. To investigate the effect of Activin B on vibrissae follicles, the anagen induction assay and an in vitro vibrissae culture system were constructed. Hematoxylin and eosin staining were performed to determine the hair cycle stages. The 5-ethynyl-2′-deoxyuridine (EdU) and Cell Counting Kit-8 (CCK-8) assays were used to examine the cell proliferation. Flow cytometry was used to detect the cell cycle phase. Inhibitors and Western blot analysis were used to investigate the signaling pathway induced by Activin B. As a result, we found that the vibrissae follicle growth was accelerated by 10 ng/mL Activin B in the anagen induction assay and in an organ culture model. 10 ng/mL Activin B promoted hair matrix cell proliferation in vivo and in vitro. Moreover, Activin B modulates hair matrix cell growth through the ERK–Elk1 signaling pathway, and Activin B accelerates hair matrix cell transition from the G1/G0 phase to the S phase through the ERK–Cyclin D1 signaling pathway. Taken together, these results demonstrated that Activin B may promote mouse vibrissae growth by stimulating hair matrix cell proliferation and cell cycle progression through ERK signaling. Full article
(This article belongs to the Special Issue MAPK-ERK Pathway)
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Open AccessArticle
Vanillic Acid Suppresses HIF-1α Expression via Inhibition of mTOR/p70S6K/4E-BP1 and Raf/MEK/ERK Pathways in Human Colon Cancer HCT116 Cells
Int. J. Mol. Sci. 2019, 20(3), 465; https://doi.org/10.3390/ijms20030465
Received: 10 December 2018 / Revised: 11 January 2019 / Accepted: 15 January 2019 / Published: 22 January 2019
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Abstract
Hypoxia-inducible factor 1 (HIF-1) plays a pivotal role in tumor adaptation to microenvironmental hypoxia, and it also exerts important roles in angiogenesis and tumor development. Vanillic acid is a dietary phenolic compound reported to exhibit anticancer properties. However, the mechanisms by which vanillic [...] Read more.
Hypoxia-inducible factor 1 (HIF-1) plays a pivotal role in tumor adaptation to microenvironmental hypoxia, and it also exerts important roles in angiogenesis and tumor development. Vanillic acid is a dietary phenolic compound reported to exhibit anticancer properties. However, the mechanisms by which vanillic acid inhibits tumor growth are not fully understood. Here, we investigated the effect of vanillic acid on HIF-1α activation. Vanillic acid significantly inhibits HIF-1α expression induced by hypoxia in various human cancer cell lines. Further analysis revealed that vanillic acid inhibited HIF-1α protein synthesis. Neither the HIF-1α protein degradation rate nor the steady-state HIF-1α mRNA levels were affected by vanillic acid. Moreover, vanillic acid inhibited HIF-1α expression by suppressing mammalian target of rapamycin/p70 ribosomal protein S6 kinase/eukaryotic initiation factor 4E-binding protein-1 and Raf/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathways. We found that vanillic acid dose-dependently inhibited VEGF and EPO protein expressions and disrupted tube formation. The results suggest that vanillic acid effectively inhibits angiogenesis. Flow cytometry analysis demonstrated that vanillic acid significantly induced G1 phase arrest and inhibited the proliferation of human colon cancer HCT116 cells. In vivo experiments confirmed that vanillic acid treatment caused significant inhibition of tumor growth in a xenografted tumor model. These studies reveal that vanillic acid is an effective inhibitor of HIF-1α and provides new perspectives into the mechanism of its antitumor activity. Full article
(This article belongs to the Special Issue MAPK-ERK Pathway)
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Graphical abstract

Review

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Open AccessReview
Human DNA Virus Exploitation of the MAPK-ERK Cascade
Int. J. Mol. Sci. 2019, 20(14), 3427; https://doi.org/10.3390/ijms20143427
Received: 31 May 2019 / Revised: 9 July 2019 / Accepted: 11 July 2019 / Published: 12 July 2019
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Abstract
The extracellular signal-regulated kinases (ERKs) comprise a particular branch of the mitogen-activated protein kinase cascades (MAPK) that transmits extracellular signals into the intracellular environment to trigger cellular growth responses. Similar to other MAPK cascades, the MAPK-ERK pathway signals through three core kinases—Raf, MAPK/ERK [...] Read more.
The extracellular signal-regulated kinases (ERKs) comprise a particular branch of the mitogen-activated protein kinase cascades (MAPK) that transmits extracellular signals into the intracellular environment to trigger cellular growth responses. Similar to other MAPK cascades, the MAPK-ERK pathway signals through three core kinases—Raf, MAPK/ERK kinase (MEK), and ERK—which drive the signaling mechanisms responsible for the induction of cellular responses from extracellular stimuli including differentiation, proliferation, and cellular survival. However, pathogens like DNA viruses alter MAPK-ERK signaling in order to access DNA replication machineries, induce a proliferative state in the cell, or even prevent cell death mechanisms in response to pathogen recognition. Differential utilization of this pathway by multiple DNA viruses highlights the dynamic nature of the MAPK-ERK pathway within the cell and the importance of its function in regulating a wide variety of cellular fates that ultimately influence viral infection and, in some cases, result in tumorigenesis. Full article
(This article belongs to the Special Issue MAPK-ERK Pathway)
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Open AccessReview
Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial–Mesenchymal Transition in Cancer
Int. J. Mol. Sci. 2019, 20(12), 2885; https://doi.org/10.3390/ijms20122885
Received: 28 May 2019 / Revised: 9 June 2019 / Accepted: 11 June 2019 / Published: 13 June 2019
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Abstract
Epithelial–mesenchymal transition (EMT) is a reversible cellular process, characterized by changes in gene expression and activation of proteins, favoring the trans-differentiation of the epithelial phenotype to a mesenchymal phenotype. This process increases cell migration and invasion of tumor cells, progression of the cell [...] Read more.
Epithelial–mesenchymal transition (EMT) is a reversible cellular process, characterized by changes in gene expression and activation of proteins, favoring the trans-differentiation of the epithelial phenotype to a mesenchymal phenotype. This process increases cell migration and invasion of tumor cells, progression of the cell cycle, and resistance to apoptosis and chemotherapy, all of which support tumor progression. One of the signaling pathways involved in tumor progression is the MAPK pathway. Within this family, the ERK subfamily of proteins is known for its contributions to EMT. The ERK subfamily is divided into typical (ERK 1/2/5), and atypical (ERK 3/4/7/8) members. These kinases are overexpressed and hyperactive in various types of cancer. They regulate diverse cellular processes such as proliferation, migration, metastasis, resistance to chemotherapy, and EMT. In this context, in vitro and in vivo assays, as well as studies in human patients, have shown that ERK favors the expression, function, and subcellular relocalization of various proteins that regulate EMT, thus promoting tumor progression. In this review, we discuss the mechanistic roles of the ERK subfamily members in EMT and tumor progression in diverse biological systems. Full article
(This article belongs to the Special Issue MAPK-ERK Pathway)
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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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