Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
Notch Signaling Pathways
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Notch Signaling Pathways

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

Deadline for manuscript submissions: closed (20 November 2024) | Viewed by 5868

Special Issue Editor

Dr. Marcia Bellon

E-Mail Website
Guest Editor
Department of Pathology, Center for Viral Pathogenesis, University of Kansas Medical Center, Kansas City, KS 66160, USA
Interests: ATL; HTLV; Tax; leukemia; lymphoma; Pim; Notch; JAK; STAT; microRNA; lncRNA, molecular biology; virus

Special Issue Information

Dear Colleagues,

Notch signal transduction is an evolutionarily conserved pathway in multicellular organisms. It regulates cell fate decisions during development and maintains the balance of adult tissues. The Notch pathway mediates parallel cellular signaling, and through the ligand–receptor crosstalk, both signal-sending and -receiving cells are affected, thereby regulating a series of cell fate decisions in neuronal, cardiac, immune and endocrine development processes. The Notch pathway is also a key cancer driver and is important in tumor progression in certain cell types, while being tumor-prohibitive in others. Early research suggests that Notch activity is highly dependent on the expression of the intracellular cleaved domain of Notch-1 (NICD). However, recent insights into Notch signaling reveal the presence of Notch pathway signatures, which may vary depending on different cancer types and environments. Indeed, the Notch pathway has become exceedingly complex, with canonical and noncanonical Notch signaling and crosstalk with various key cellular signaling pathways. Due to its role in disease and cancer, Notch signaling is an attractive target for therapeutic intervention.

This Special Issue aims to attract contributions on all aspects of the role of the Notch signaling pathway in the tumor microenvironment, neuronal, cardiac, immune and endocrine development processes. Emphasis will be placed on new research articles related to Notch therapeutics in disease and cancer, and the regulation of Notch signaling in tumor development and progression.

Dr. Marcia Bellon
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 submissions that pass pre-check are 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

  • Notch signaling
  • Notch and the tumor microenvironment
  • Notch therapeutics
  • Notch neuronal aspects
  • Notch cardiac aspects
  • Notch immune aspects
  • Notch endocrine development processes
  • Notch and stem cells
  • Notch single cell analysis
  • Notch noncanonical signaling pathways
  • Notch as a tumor suppressor

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

15 pages, 2802 KiB  
Article
Somatic Recombination Between an Ancient and a Recent NOTCH2 Gene Variant is Associated with the NOTCH2 Gain-of-Function Phenotype in Chronic Lymphocytic Leukemia
by Rainer Hubmann, Martin Hilgarth, Tamara Löwenstern, Andrea Lienhard, Filip Sima, Manuel Reisinger, Claudia Hobel-Kleisch, Edit Porpaczy, Torsten Haferlach, Gregor Hoermann, Franco Laccone, Christof Jungbauer, Peter Valent, Philipp B. Staber, Medhat Shehata and Ulrich Jäger
Int. J. Mol. Sci. 2024, 25(23), 12581; https://doi.org/10.3390/ijms252312581 - 22 Nov 2024
Viewed by 305
Abstract
Constitutively active NOTCH2 signaling is a hallmark in chronic lymphocytic leukemia (CLL). The precise underlying defect remains obscure. Here we show that the mRNA sequence coding for the NOTCH2 negative regulatory region (NRR) is consistently deleted in CLL cells. The most common NOTCH2ΔNRR-DEL2 [...] Read more.
Constitutively active NOTCH2 signaling is a hallmark in chronic lymphocytic leukemia (CLL). The precise underlying defect remains obscure. Here we show that the mRNA sequence coding for the NOTCH2 negative regulatory region (NRR) is consistently deleted in CLL cells. The most common NOTCH2ΔNRR-DEL2 deletion is associated with two intronic single nucleotide variations (SNVs) which either create (CTTAT, G>A for rs2453058) or destroy (CTCGT, A>G for rs5025718) a putative splicing branch point sequence (BPS). Phylogenetic analysis demonstrates that rs2453058 is part of an ancient NOTCH2 gene variant (*1A01) which is associated with type 2 diabetes mellitus (T2DM) and is two times more frequent in Europeans than in East Asians, resembling the differences in CLL incidence. In contrast, rs5025718 belongs to a recent NOTCH2 variant (*1a4) that dominates the world outside Africa. Nanopore sequencing indicates that somatic reciprocal crossing over between rs2453058 (*1A01) and rs5025718 (*1a4) leads to recombined NOTCH2 alleles with altered BPS patterns in NOTCH2*1A01/*1a4 CLL cases. This would explain the loss of the NRR domain by aberrant pre-mRNA splicing and consequently the NOTCH2 gain-of-function phenotype. Together, our findings suggest that somatic recombination of inherited NOTCH2 variants might be relevant to CLL etiology and may at least partly explain its geographical clustering. Full article
(This article belongs to the Special Issue Notch Signaling Pathways)
13 pages, 2539 KiB  
Article
Differential Effects of Four Canonical Notch-Activating Ligands on c-Kit+ Cardiac Progenitor Cells
by Matthew Robeson, Steven L. Goudy and Michael E. Davis
Int. J. Mol. Sci. 2024, 25(20), 11182; https://doi.org/10.3390/ijms252011182 - 17 Oct 2024
Viewed by 674
Abstract
Notch signaling, an important signaling pathway in cardiac development, has been shown to mediate the reparative functions of c-kit+ progenitor cells (CPCs). However, it is unclear how each of the four canonical Notch-activating ligands affects intracellular processes in c-kit+ cells when used as [...] Read more.
Notch signaling, an important signaling pathway in cardiac development, has been shown to mediate the reparative functions of c-kit+ progenitor cells (CPCs). However, it is unclear how each of the four canonical Notch-activating ligands affects intracellular processes in c-kit+ cells when used as an external stimulus. Neonatal c-kit+ CPCs were stimulated using four different chimeric Notch-activating ligands tethered to Dynabeads, and the resulting changes were assessed using TaqMan gene expression arrays, with subsequent analysis by principal component analysis (PCA). Additionally, functional outcomes were measured using an endothelial cell tube formation assay and MSC migration assay to assess the paracrine capacity to stimulate new vessel formation and recruit other reparative cell types to the site of injury. Gene expression data showed that stimulation with Jagged-1 is associated with the greatest pro-angiogenic gene response, including the expression of VEGF and basement membrane proteins, while the other canonical ligands, Jagged-2, Dll-1, and Dll-4, are more associated with regulatory and epigenetic changes. The functional assay showed differential responses to the four ligands in terms of angiogenesis, while none of the ligands produced a robust change in migration. These data demonstrate how the four Notch-activating ligands differentially regulate CPC gene expression and function. Full article
(This article belongs to the Special Issue Notch Signaling Pathways)
►▼ Show Figures

Figure 1

20 pages, 2972 KiB  
Article
Increased H19/miR-675 Expression in Adult T-Cell Leukemia Is Associated with a Unique Notch Signature Pathway
by Marcia Bellon and Christophe Nicot
Int. J. Mol. Sci. 2024, 25(10), 5130; https://doi.org/10.3390/ijms25105130 - 8 May 2024
Viewed by 1464
Abstract
The Notch pathway is a key cancer driver and is important in tumor progression. Early research suggested that Notch activity was highly dependent on the expression of the intracellular cleaved domain of Notch-1 (NICD). However, recent insights into Notch signaling reveal the presence [...] Read more.
The Notch pathway is a key cancer driver and is important in tumor progression. Early research suggested that Notch activity was highly dependent on the expression of the intracellular cleaved domain of Notch-1 (NICD). However, recent insights into Notch signaling reveal the presence of Notch pathway signatures, which may vary depending on different cancer types and tumor microenvironments. Herein, we perform a comprehensive investigation of the Notch signaling pathway in adult T-cell leukemia (ATL) primary patient samples. Using gene arrays, we demonstrate that the Notch pathway is constitutively activated in ATL patient samples. Furthermore, the activation of Notch in ATL cells remains elevated irrespective of the presence of activating mutations in Notch itself or its repressor, FBXW7, and that ATL cells are dependent upon Notch-1 expression for proliferation and survival. We demonstrate that ATL cells exhibit the expression of pivotal Notch-related genes, including notch-1, hes1, c-myc, H19, and hes4, thereby defining a critical Notch signature associated with ATL disease. Finally, we demonstrate that lncRNA H19 is highly expressed in ATL patient samples and ATL cells and contributes to Notch signaling activation. Collectively, our results shed further light on the Notch pathway in ATL leukemia and reveal new therapeutic approaches to inhibit Notch activation in ATL cells. Full article
(This article belongs to the Special Issue Notch Signaling Pathways)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop