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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pagliaro, Luca, Sorrentino, Claudia, Roti, Giovanni
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