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Notch3 in Development, Health and Disease
Notch3 is one of four mammalian Notch proteins, which act as signalling receptors to control cell fate in many developmental and adult tissue contexts. Notch signalling continues to be important in the adult organism for tissue maintenance and renewal and mis-regulation of Notch is involved in many...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175233/ https://www.ncbi.nlm.nih.gov/pubmed/32210034 http://dx.doi.org/10.3390/biom10030485 |
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author | Hosseini-Alghaderi, Samira Baron, Martin |
author_facet | Hosseini-Alghaderi, Samira Baron, Martin |
author_sort | Hosseini-Alghaderi, Samira |
collection | PubMed |
description | Notch3 is one of four mammalian Notch proteins, which act as signalling receptors to control cell fate in many developmental and adult tissue contexts. Notch signalling continues to be important in the adult organism for tissue maintenance and renewal and mis-regulation of Notch is involved in many diseases. Genetic studies have shown that Notch3 gene knockouts are viable and have limited developmental defects, focussed mostly on defects in the arterial smooth muscle cell lineage. Additional studies have revealed overlapping roles for Notch3 with other Notch proteins, which widen the range of developmental functions. In the adult, Notch3, in collaboration with other Notch proteins, is involved in stem cell regulation in different tissues in stem cell regulation in different tissues, and it also controls the plasticity of the vascular smooth muscle phenotype involved in arterial vessel remodelling. Overexpression, gene amplification and mis-activation of Notch3 are associated with different cancers, in particular triple negative breast cancer and ovarian cancer. Mutations of Notch3 are associated with a dominantly inherited disease CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy), and there is further evidence linking Notch3 misregulation to hypertensive disease. Here we discuss the distinctive roles of Notch3 in development, health and disease, different views as to the underlying mechanisms of its activation and misregulation in different contexts and potential for therapeutic intervention. |
format | Online Article Text |
id | pubmed-7175233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71752332020-04-28 Notch3 in Development, Health and Disease Hosseini-Alghaderi, Samira Baron, Martin Biomolecules Review Notch3 is one of four mammalian Notch proteins, which act as signalling receptors to control cell fate in many developmental and adult tissue contexts. Notch signalling continues to be important in the adult organism for tissue maintenance and renewal and mis-regulation of Notch is involved in many diseases. Genetic studies have shown that Notch3 gene knockouts are viable and have limited developmental defects, focussed mostly on defects in the arterial smooth muscle cell lineage. Additional studies have revealed overlapping roles for Notch3 with other Notch proteins, which widen the range of developmental functions. In the adult, Notch3, in collaboration with other Notch proteins, is involved in stem cell regulation in different tissues in stem cell regulation in different tissues, and it also controls the plasticity of the vascular smooth muscle phenotype involved in arterial vessel remodelling. Overexpression, gene amplification and mis-activation of Notch3 are associated with different cancers, in particular triple negative breast cancer and ovarian cancer. Mutations of Notch3 are associated with a dominantly inherited disease CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy), and there is further evidence linking Notch3 misregulation to hypertensive disease. Here we discuss the distinctive roles of Notch3 in development, health and disease, different views as to the underlying mechanisms of its activation and misregulation in different contexts and potential for therapeutic intervention. MDPI 2020-03-23 /pmc/articles/PMC7175233/ /pubmed/32210034 http://dx.doi.org/10.3390/biom10030485 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Hosseini-Alghaderi, Samira Baron, Martin Notch3 in Development, Health and Disease |
title | Notch3 in Development, Health and Disease |
title_full | Notch3 in Development, Health and Disease |
title_fullStr | Notch3 in Development, Health and Disease |
title_full_unstemmed | Notch3 in Development, Health and Disease |
title_short | Notch3 in Development, Health and Disease |
title_sort | notch3 in development, health and disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175233/ https://www.ncbi.nlm.nih.gov/pubmed/32210034 http://dx.doi.org/10.3390/biom10030485 |
work_keys_str_mv | AT hosseinialghaderisamira notch3indevelopmenthealthanddisease AT baronmartin notch3indevelopmenthealthanddisease |