Premium
Usp2–45 represses aldosterone response by decreasing mineralocorticoid receptor availability
Author(s) -
Staub Olivier,
Debonneville Anne,
Pouly Daniel,
Faresse Nourdine
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1115.23
Subject(s) - tsg101 , mineralocorticoid receptor , aldosterone , ubiquitin , receptor , mineralocorticoid , endocrinology , transcription factor , chemistry , medicine , biology , cancer research , microbiology and biotechnology , gene , biochemistry , microrna , microvesicles
Steroid receptors are known to be subject to dynamic ubiquitylation that impacts their stability and activity as transcription factors. We have previously described that the mineralocorticoid receptor (MR) is monoubiquitylated in its basal state and this status is sustained by the tumor suppressor gene 101 (Tsg101) bound to the ubiquitylated receptor. Aldosterone stimulation of MR induced monoubiquitylation removal and disruption of MR/Tsg101 association that prompt polyubiquitin‐dependent destabilization of MR and proteasomal degradation. In this study, we found that the aldosterone induced ubiquitin‐specific protease USP2–45 has a pivotal role in the regulation of MR ubiquitylation state. This enzyme is able to bind to MR and mimic aldosterone effects by inducing MR monoubiquitylation removal, disruption of MR/Tsg101 association and destabilization of MR at protein level. Hence, this study demonstrates a new role for USP2–45 and reveals the existence of a negative feedback loop for limiting aldosterone induced response.