Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension
Ubiquitination is a representative, reversible biological process of the post-translational modification of various proteins with multiple catalytic reaction sequences, including ubiquitin itself, in addition to E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, E3 ubiquitin ligase,...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/11/3871 |
| _version_ | 1797566683860172800 |
|---|---|
| author | Tomoaki Ishigami Tabito Kino Shintaro Minegishi Naomi Araki Masanari Umemura Hisako Ushio Sae Saigoh Michiko Sugiyama |
| author_facet | Tomoaki Ishigami Tabito Kino Shintaro Minegishi Naomi Araki Masanari Umemura Hisako Ushio Sae Saigoh Michiko Sugiyama |
| author_sort | Tomoaki Ishigami |
| collection | DOAJ |
| description | Ubiquitination is a representative, reversible biological process of the post-translational modification of various proteins with multiple catalytic reaction sequences, including ubiquitin itself, in addition to E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, E3 ubiquitin ligase, deubiquitinating enzymes, and proteasome degradation. The ubiquitin–proteasome system is known to play a pivotal role in various molecular life phenomena, including the cell cycle, protein quality, and cell surface expressions of ion-transporters. As such, the failure of this system can lead to cancer, neurodegenerative diseases, cardiovascular diseases, and hypertension. This review article discusses <i>Nedd4-2</i>/<i>NEDD4L,</i> an E3-ubiquitin ligase involved in salt-sensitive hypertension, drawing from detailed genetic dissection analysis and the development of genetically engineered mice model. Based on our analyses, targeting therapeutic regulations of ubiquitination in the fields of cardio-vascular medicine might be a promising strategy in future. Although the clinical applications of this strategy are limited, compared to those of kinase systems, many compounds with a high pharmacological activity were identified at the basic research level. Therefore, future development could be expected. |
| first_indexed | 2024-03-10T19:30:58Z |
| format | Article |
| id | doaj.art-b46ba92bd34545a1bac368b7dc156b5e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:30:58Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b46ba92bd34545a1bac368b7dc156b5e2023-11-20T02:09:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012111387110.3390/ijms21113871Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive HypertensionTomoaki Ishigami0Tabito Kino1Shintaro Minegishi2Naomi Araki3Masanari Umemura4Hisako Ushio5Sae Saigoh6Michiko Sugiyama7Department of Medical Science and Cardio-Renal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, Kanazawa-Ku 236-0004, JapanDepartment of Medical Science and Cardio-Renal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, Kanazawa-Ku 236-0004, JapanDepartment of Medical Science and Cardio-Renal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, Kanazawa-Ku 236-0004, JapanDepartment of Medical Science and Cardio-Renal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, Kanazawa-Ku 236-0004, JapanDepartment of Medical Science and Cardio-Renal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, Kanazawa-Ku 236-0004, JapanDepartment of Medical Science and Cardio-Renal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, Kanazawa-Ku 236-0004, JapanDepartment of Medical Science and Cardio-Renal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, Kanazawa-Ku 236-0004, JapanDepartment of Medical Science and Cardio-Renal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, Kanazawa-Ku 236-0004, JapanUbiquitination is a representative, reversible biological process of the post-translational modification of various proteins with multiple catalytic reaction sequences, including ubiquitin itself, in addition to E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, E3 ubiquitin ligase, deubiquitinating enzymes, and proteasome degradation. The ubiquitin–proteasome system is known to play a pivotal role in various molecular life phenomena, including the cell cycle, protein quality, and cell surface expressions of ion-transporters. As such, the failure of this system can lead to cancer, neurodegenerative diseases, cardiovascular diseases, and hypertension. This review article discusses <i>Nedd4-2</i>/<i>NEDD4L,</i> an E3-ubiquitin ligase involved in salt-sensitive hypertension, drawing from detailed genetic dissection analysis and the development of genetically engineered mice model. Based on our analyses, targeting therapeutic regulations of ubiquitination in the fields of cardio-vascular medicine might be a promising strategy in future. Although the clinical applications of this strategy are limited, compared to those of kinase systems, many compounds with a high pharmacological activity were identified at the basic research level. Therefore, future development could be expected.https://www.mdpi.com/1422-0067/21/11/3871salt-sensitive hypertensionubiquitinationNedd4L/Nedd4-2epithelial sodium channelaldosterone sensitive distal nephronexcitation-transcription coupling |
| spellingShingle | Tomoaki Ishigami Tabito Kino Shintaro Minegishi Naomi Araki Masanari Umemura Hisako Ushio Sae Saigoh Michiko Sugiyama Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension International Journal of Molecular Sciences salt-sensitive hypertension ubiquitination Nedd4L/Nedd4-2 epithelial sodium channel aldosterone sensitive distal nephron excitation-transcription coupling |
| title | Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension |
| title_full | Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension |
| title_fullStr | Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension |
| title_full_unstemmed | Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension |
| title_short | Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension |
| title_sort | regulators of epithelial sodium channels in aldosterone sensitive distal nephrons asdn critical roles of nedd4l nedd4 2 and salt sensitive hypertension |
| topic | salt-sensitive hypertension ubiquitination Nedd4L/Nedd4-2 epithelial sodium channel aldosterone sensitive distal nephron excitation-transcription coupling |
| url | https://www.mdpi.com/1422-0067/21/11/3871 |
| work_keys_str_mv | AT tomoakiishigami regulatorsofepithelialsodiumchannelsinaldosteronesensitivedistalnephronsasdncriticalrolesofnedd4lnedd42andsaltsensitivehypertension AT tabitokino regulatorsofepithelialsodiumchannelsinaldosteronesensitivedistalnephronsasdncriticalrolesofnedd4lnedd42andsaltsensitivehypertension AT shintarominegishi regulatorsofepithelialsodiumchannelsinaldosteronesensitivedistalnephronsasdncriticalrolesofnedd4lnedd42andsaltsensitivehypertension AT naomiaraki regulatorsofepithelialsodiumchannelsinaldosteronesensitivedistalnephronsasdncriticalrolesofnedd4lnedd42andsaltsensitivehypertension AT masanariumemura regulatorsofepithelialsodiumchannelsinaldosteronesensitivedistalnephronsasdncriticalrolesofnedd4lnedd42andsaltsensitivehypertension AT hisakoushio regulatorsofepithelialsodiumchannelsinaldosteronesensitivedistalnephronsasdncriticalrolesofnedd4lnedd42andsaltsensitivehypertension AT saesaigoh regulatorsofepithelialsodiumchannelsinaldosteronesensitivedistalnephronsasdncriticalrolesofnedd4lnedd42andsaltsensitivehypertension AT michikosugiyama regulatorsofepithelialsodiumchannelsinaldosteronesensitivedistalnephronsasdncriticalrolesofnedd4lnedd42andsaltsensitivehypertension |