Cargando…
Targeting Notch Trafficking and Processing in Cancers
The Notch family comprises a group of four ligand-dependent receptors that control evolutionarily conserved developmental and homeostatic processes and transmit signals to the microenvironment. NOTCH undergoes remodeling, maturation, and trafficking in a series of post-translational events, includin...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600097/ https://www.ncbi.nlm.nih.gov/pubmed/33003595 http://dx.doi.org/10.3390/cells9102212 |
_version_ | 1783603049205334016 |
---|---|
author | Pagliaro, Luca Sorrentino, Claudia Roti, Giovanni |
author_facet | Pagliaro, Luca Sorrentino, Claudia Roti, Giovanni |
author_sort | Pagliaro, Luca |
collection | PubMed |
description | The Notch family comprises a group of four ligand-dependent receptors that control evolutionarily conserved developmental and homeostatic processes and transmit signals to the microenvironment. NOTCH undergoes remodeling, maturation, and trafficking in a series of post-translational events, including glycosylation, ubiquitination, and endocytosis. The regulatory modifications occurring in the endoplasmic reticulum/Golgi precede the intramembrane γ-secretase proteolysis and the transfer of active NOTCH to the nucleus. Hence, NOTCH proteins coexist in different subcellular compartments and undergo continuous relocation. Various factors, including ion concentration, enzymatic activity, and co-regulatory elements control Notch trafficking. Interfering with these regulatory mechanisms represents an innovative therapeutic way to bar oncogenic Notch signaling. In this review, we briefly summarize the role of Notch signaling in cancer and describe the protein modifications required for NOTCH to relocate across different subcellular compartments. We focus on the functional relationship between these modifications and the corresponding therapeutic options, and our findings could support the development of trafficking modulators as a potential alternative to the well-known γ-secretase inhibitors. |
format | Online Article Text |
id | pubmed-7600097 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76000972020-11-01 Targeting Notch Trafficking and Processing in Cancers Pagliaro, Luca Sorrentino, Claudia Roti, Giovanni Cells Review The Notch family comprises a group of four ligand-dependent receptors that control evolutionarily conserved developmental and homeostatic processes and transmit signals to the microenvironment. NOTCH undergoes remodeling, maturation, and trafficking in a series of post-translational events, including glycosylation, ubiquitination, and endocytosis. The regulatory modifications occurring in the endoplasmic reticulum/Golgi precede the intramembrane γ-secretase proteolysis and the transfer of active NOTCH to the nucleus. Hence, NOTCH proteins coexist in different subcellular compartments and undergo continuous relocation. Various factors, including ion concentration, enzymatic activity, and co-regulatory elements control Notch trafficking. Interfering with these regulatory mechanisms represents an innovative therapeutic way to bar oncogenic Notch signaling. In this review, we briefly summarize the role of Notch signaling in cancer and describe the protein modifications required for NOTCH to relocate across different subcellular compartments. We focus on the functional relationship between these modifications and the corresponding therapeutic options, and our findings could support the development of trafficking modulators as a potential alternative to the well-known γ-secretase inhibitors. MDPI 2020-09-29 /pmc/articles/PMC7600097/ /pubmed/33003595 http://dx.doi.org/10.3390/cells9102212 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 Pagliaro, Luca Sorrentino, Claudia Roti, Giovanni Targeting Notch Trafficking and Processing in Cancers |
title | Targeting Notch Trafficking and Processing in Cancers |
title_full | Targeting Notch Trafficking and Processing in Cancers |
title_fullStr | Targeting Notch Trafficking and Processing in Cancers |
title_full_unstemmed | Targeting Notch Trafficking and Processing in Cancers |
title_short | Targeting Notch Trafficking and Processing in Cancers |
title_sort | targeting notch trafficking and processing in cancers |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600097/ https://www.ncbi.nlm.nih.gov/pubmed/33003595 http://dx.doi.org/10.3390/cells9102212 |
work_keys_str_mv | AT pagliaroluca targetingnotchtraffickingandprocessingincancers AT sorrentinoclaudia targetingnotchtraffickingandprocessingincancers AT rotigiovanni targetingnotchtraffickingandprocessingincancers |