Targeting Notch Trafficking and Processing in Cancers.
Amyloid Precursor Protein Secretases
/ metabolism
Cell Membrane
/ genetics
Endocytosis
/ genetics
Golgi Apparatus
/ metabolism
Humans
Membrane Proteins
/ metabolism
Neoplasms
/ genetics
Protein Processing, Post-Translational
/ genetics
Protein Transport
/ genetics
Receptors, Notch
/ genetics
Signal Transduction
/ genetics
CAD204520
NOTCH1
SERCA
T-cell acute lymphoblastic leukemia
thapsigargin
trafficking
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
29 09 2020
29 09 2020
Historique:
received:
06
07
2020
revised:
02
09
2020
accepted:
08
09
2020
entrez:
2
10
2020
pubmed:
3
10
2020
medline:
20
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33003595
pii: cells9102212
doi: 10.3390/cells9102212
pmc: PMC7600097
pii:
doi:
Substances chimiques
Membrane Proteins
0
Receptors, Notch
0
Amyloid Precursor Protein Secretases
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
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