USP2-45 represses aldosterone mediated responses by decreasing mineralocorticoid receptor availability.

Détails

ID Serval
serval:BIB_0FB77D8610A4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
USP2-45 represses aldosterone mediated responses by decreasing mineralocorticoid receptor availability.
Périodique
Cellular Physiology and Biochemistry
Auteur(s)
Faresse N., Debonneville A., Staub O.
ISSN
1421-9778 (Electronic)
ISSN-L
1015-8987
Statut éditorial
Publié
Date de publication
2013
Volume
31
Numéro
2-3
Pages
462-472
Langue
anglais
Résumé
BACKGROUND/AIMS: Ligand activation of the mineralocorticoid receptor (MR) induces several post-translational modifications (PTMs). Among the different PTMs, MR is known to be dynamically ubiquitylated with impact on its stability and transcriptional activity. Previously, we have shown that MR is monoubiquitylated at the basal state and that aldosterone stimulation induces monoubiquitylation removal prompting polyubiquitin-dependent destabilization of the receptor and proteasomal degradation. This study investigated the role of the aldosterone induced ubiquitin-specific protease USP2-45 on the ubiquitylation state of MR.
METHODS: Renal epithelial cells M1 were co-transfected with MR with or without wild-type or inactive USP2-45. The association of MR with USP2-45 or TSG101 as well as MR ubiquitylation state were determined by immunoprecipitation and immunoblotting. MR transcriptional activity was assessed via a luciferase reporter gene.
RESULTS: We show that USP2-45 is able to bind MR and, similarly to aldosterone, induce MR monoubiquitylation removal, disruption of MR/TSG101 association and destabilization of MR at protein level.
CONCLUSION: This study provides a novel role for USP2-45 by playing a pivotal role in the regulation of the ubiquitylation state of MR and reveals the existence of a negative feedback loop for limiting the aldosterone induced response.
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/06/2013 17:32
Dernière modification de la notice
20/10/2020 10:08
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