Dimerization modulates the activity of the orphan nuclear receptor ERRgamma
Huppunen, J.; Aarnisalo, P.
Biochemical and Biophysical Research Communications 314(4): 964-970
2004
ISSN/ISBN: 0006-291X PMID: 14751226 Document Number: 571004
Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor lacking identified natural ligands. However, 4-hydroxytam-oxifen and diethylstilbestrol were recently shown to bind to and inhibit ERRgamma activity. ERR activates transcription constitutively as a monomer. We show here that ERRgamma forms also dimers via its ligand-binding domain. Homodimerization enhances the transcriptional activity. In contrast, heterodimerization with the related receptor ERRalpha inhibits the activities of both ERRgamma and ERRalpha. The inverse ERRgamma agonist 4OHT further inhibits the activity of the ERRgamma-ERRalpha heterodimer, indicating that 4OHT may modulate ERRalpha signaling via ERRgamma. Receptor dimerization thus modulates the transcriptional activities of ERRs.