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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/10/2212 |
| _version_ | 1797552217317703680 |
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| author | Luca Pagliaro Claudia Sorrentino Giovanni Roti |
| author_facet | Luca Pagliaro Claudia Sorrentino Giovanni Roti |
| author_sort | Luca Pagliaro |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T15:56:49Z |
| format | Article |
| id | doaj.art-67a6d667646348edbac2d98e2df38a5a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T15:56:49Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-67a6d667646348edbac2d98e2df38a5a2023-11-20T15:33:53ZengMDPI AGCells2073-44092020-09-01910221210.3390/cells9102212Targeting Notch Trafficking and Processing in CancersLuca Pagliaro0Claudia Sorrentino1Giovanni Roti2Department of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyThe 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.https://www.mdpi.com/2073-4409/9/10/2212NOTCH1SERCAT-cell acute lymphoblastic leukemiathapsigargintraffickingCAD204520 |
| spellingShingle | Luca Pagliaro Claudia Sorrentino Giovanni Roti Targeting Notch Trafficking and Processing in Cancers Cells NOTCH1 SERCA T-cell acute lymphoblastic leukemia thapsigargin trafficking CAD204520 |
| 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 | NOTCH1 SERCA T-cell acute lymphoblastic leukemia thapsigargin trafficking CAD204520 |
| url | https://www.mdpi.com/2073-4409/9/10/2212 |
| work_keys_str_mv | AT lucapagliaro targetingnotchtraffickingandprocessingincancers AT claudiasorrentino targetingnotchtraffickingandprocessingincancers AT giovanniroti targetingnotchtraffickingandprocessingincancers |