REV-ERBα influences the stability and nuclear localization of the glucocorticoid receptor.
REV-ERBα (encoded by Nr1d1) is a nuclear receptor that is part of the circadian clock mechanism and regulates metabolism and inflammatory processes. The glucocorticoid receptor (GR, encoded by Nr3c1) influences similar processes, but is not part of the circadian clock, although glucocorticoid signaling affects resetting of the circadian clock in peripheral tissues. Because of their similar impact on physiological processes, we studied the interplay between these two nuclear receptors. We found that REV-ERBα binds to the C-terminal portion and GR to the N-terminal portion of HSP90α and HSP90β, a chaperone responsible for the activation of proteins to ensure survival of a cell. The presence of REV-ERBα influences the stability and nuclear localization of GR by an unknown mechanism, thereby affecting expression of GR target genes, such as IκBα (Nfkbia) and alcohol dehydrogenase 1 (Adh1). Our findings highlight an important interplay between two nuclear receptors that influence the transcriptional potential of each other. This indicates that the transcriptional landscape is strongly dependent on dynamic processes at the protein level.
Dept. of Biology, Biochemistry, University of Fribourg, Fribourg 1700, Switzerland.
Takashi
T
Okabe
Dept. of Biology, Biochemistry, University of Fribourg, Fribourg 1700, Switzerland.
Rohit
R
Chavan
Dept. of Biology, Biochemistry, University of Fribourg, Fribourg 1700, Switzerland.
Sara S
SS
Fonseca Costa
Dept. of Biology, Biochemistry, University of Fribourg, Fribourg 1700, Switzerland.
Andrea
A
Brenna
Dept. of Biology, Biochemistry, University of Fribourg, Fribourg 1700, Switzerland.
Jürgen A
JA
Ripperger
Dept. of Biology, Biochemistry, University of Fribourg, Fribourg 1700, Switzerland urs.albrecht@unifr.ch.
Urs
0000-0002-0663-8676
U
Albrecht
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D002940:Circadian Rhythm; D005786:Gene Expression Regulation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
D018841:HSP90 Heat-Shock Proteins; C498262:Nr1d1 protein, mouse; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid
Circadian clock; Glucocorticoid receptor; HSP90; Nuclear receptor; REV-ERBα
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