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

Details

Serval ID
serval:BIB_0FB77D8610A4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
USP2-45 represses aldosterone mediated responses by decreasing mineralocorticoid receptor availability.
Journal
Cellular Physiology and Biochemistry
Author(s)
Faresse N., Debonneville A., Staub O.
ISSN
1421-9778 (Electronic)
ISSN-L
1015-8987
Publication state
Published
Issued date
2013
Volume
31
Number
2-3
Pages
462-472
Language
english
Abstract
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
Yes
Create date
13/06/2013 17:32
Last modification date
20/10/2020 10:08
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