Linked Life Data

15171715

Source:http://linkedlifedata.com/resource/pubmed/id/15171715

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-6-2
pubmed:abstractText
Corticosteroid actions in the brain are exerted via the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). These receptors share several structural and functional similarities but their activation in the brain triggers distinct biological actions, for instance on neuronal survival or the regulation of the hypothalamo-pituitary-adrenal axis. Like other hormone-activated receptors, the transcriptional properties of the MR and GR depend on their ability to recruit a variety of co-regulators, which modulate their activity on target promoters, in a specific manner. The N-terminal regions of the MR and GR share the smallest degree of sequence conservation, whereas they display opposite effects on the transactivation properties of these receptors; thus, they may provide surfaces suitable for receptorspecific interactions with co-regulatory proteins. Here, we employed a yeast two-hybrid system to identify molecules interacting with the N-terminal part of the MR (amino acids 170-433). This approach resulted in the isolation of representative cDNAs from all members of the protein inhibitor of activated STAT (PIAS) family of proteins as potential MR-interacting partners. In neural cells, PIAS3 exhibited a strong and specific interaction with MR, but not GR, as indicated by mammalian two-hybrid assays and co-immunoprecipitation experiments in vivo. The interaction with MR was enhanced in the presence of aldosterone, an MR agonist, and was found to occur through a conserved, serine- and acidic amino acid residue-rich domain of PIAS3. To compare the modulatory properties of PIAS proteins on MR and GR transcriptional activity in a neural environment, MMTV reporter gene assays were performed in the human neuroblastoma cell line SK-N-MC. This analysis revealed that PIAS3 can inhibit MR, but not GR, transactivation in response to their corresponding ligands. Further, it showed that PIAS1 and PIASxbeta, but not PIASy, could also inhibit MR-mediated transcription despite the lack of detected physical interaction with MR. Interestingly, PIASxbeta and PIASy dose-dependently co-activated GR, whereas PIAS1 impaired GR-induced transcription. Taken together the results reveal differential modulatory roles of the PIAS proteins on the transcriptional properties of MR and GR, thus providing new insights into the bifurcating actions of these two receptors in neural cells where they are frequently co-localized.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0952-5041
pubmed:author
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
825-41
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
The manifold actions of the protein inhibitor of activated STAT proteins on the transcriptional activity of mineralocorticoid and glucocorticoid receptors in neural cells.
pubmed:affiliation
Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 Munich, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't