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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,...

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Autores principales: Ishigami, Tomoaki, Kino, Tabito, Minegishi, Shintaro, Araki, Naomi, Umemura, Masanari, Ushio, Hisako, Saigoh, Sae, Sugiyama, Michiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312533/
https://www.ncbi.nlm.nih.gov/pubmed/32485919
http://dx.doi.org/10.3390/ijms21113871
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author Ishigami, Tomoaki
Kino, Tabito
Minegishi, Shintaro
Araki, Naomi
Umemura, Masanari
Ushio, Hisako
Saigoh, Sae
Sugiyama, Michiko
author_facet Ishigami, Tomoaki
Kino, Tabito
Minegishi, Shintaro
Araki, Naomi
Umemura, Masanari
Ushio, Hisako
Saigoh, Sae
Sugiyama, Michiko
author_sort Ishigami, Tomoaki
collection PubMed
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 Nedd4-2/NEDD4L, 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.
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spelling pubmed-73125332020-06-29 Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension Ishigami, Tomoaki Kino, Tabito Minegishi, Shintaro Araki, Naomi Umemura, Masanari Ushio, Hisako Saigoh, Sae Sugiyama, Michiko Int J Mol Sci Review 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 Nedd4-2/NEDD4L, 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. MDPI 2020-05-29 /pmc/articles/PMC7312533/ /pubmed/32485919 http://dx.doi.org/10.3390/ijms21113871 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
Ishigami, Tomoaki
Kino, Tabito
Minegishi, Shintaro
Araki, Naomi
Umemura, Masanari
Ushio, Hisako
Saigoh, Sae
Sugiyama, Michiko
Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension
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 Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312533/
https://www.ncbi.nlm.nih.gov/pubmed/32485919
http://dx.doi.org/10.3390/ijms21113871
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