Phosphorylation alters Oestrogen Receptor beta-mediated transcription in neurons Journal Article

Authors: Pinceti, E.; Shults, C. L.; Rao, Y. S.; Mott, N. N.; Pak, T. R.
Article Title: Phosphorylation alters Oestrogen Receptor beta-mediated transcription in neurons
Abstract: Nuclear steroid hormone receptors are ubiquitously expressed transcription factors whose activity can be altered by post-translational modifications, such as phosphorylation. The consequences of post-translational modifications have been described for several members of the nuclear steroid hormone receptor superfamily, however little is known about the effects of oestrogen receptor beta (ERbeta) phosphorylation in the brain. Moreover, to our knowledge the presence of phosphorylated ERbeta has not been detected in the brain of any species to date. Oestrogen receptor beta is highly expressed in several regions of the brain and in vitro studies have demonstrated that it can be phosphorylated at two serine residues (S87 and S105) in the N-terminal AF-1 region. The goal of this study was to determine whether phosphorylated ERbeta is detectable in the hippocampus of aged female rats, and to determine the functional consequences of ERbeta S87 and S105 phosphorylation on transcriptional activity in neuronal cells. First, we used a novel PhosTag approach to detect phosphorylated forms of ERbeta in the dorsal hippocampus of aged female rats. The data demonstrated several abundant forms of phosphorylated ERbeta in the dorsal hippocampus, suggesting that this post translational modification might be an important regulator of ERbeta function. To assess the functional consequences of ERbeta phosphorylation in neuronal cells, we created phospho-mimetic (S87E, S105E) and phospho-null (S87A, S105A) ERbeta receptors that were transiently transfected in a hippocampal-derived cell line. Collectively our results showed that phosphorylation of S87 and S105 altered both ligand-independent and ligand-dependent ERbeta transcriptional regulation. Overall these data demonstrate that phosphorylated forms of ERbeta are present in the brain of aged female rats and that phosphorylation of ERbeta could differentially alter ERbeta-mediated gene expression. This article is protected by copyright. All rights reserved.
Journal Title: Journal of neuroendocrinology
ISSN: 1365-2826; 0953-8194
Publisher: Unknown  
Date Published: 2015
Language: ENG
Notes: LR: 20151019; CI: This article is protected by copyright. All rights reserved.; GR: R01 AG033605/AG/NIA NIH HHS/United States; JID: 8913461; OTO: NOTNLM; 2015/04/07 [received]; 2015/09/21 [revised]; 2015/09/29 [accepted]; aheadofprint