Linked Life Data

11518808

Source:http://linkedlifedata.com/resource/pubmed/id/11518808

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-8-23
pubmed:abstractText
Aldosterone effects are mediated by the MR, which possesses the same affinity for mineralocorticoids and glucocorticoids. In addition to the existence of mechanisms regulating intracellular hormone availability, we searched for human MR splice variants involved in tissue-specific corticosteroid function. We have identified a new human MR isoform, hMRDelta5,6, resulting from an alternative splicing event skipping exons 5 and 6 of the human MR gene. hMRDelta5,6 mRNAs are expressed in several human tissues at different levels compared with wild-type human MR, as shown by real time PCR. Introduction of a premature stop codon results in a 75-kDa protein lacking the entire hinge region and ligand binding domain. Interestingly, hMRDelta5,6 is still capable of binding to DNA and acts as a ligand-independent transactivator, with maximal transcriptional induction corresponding to approximately 30-40% of aldosterone-activated wild-type human MR. Coexpression of hMRDelta5,6 with human MR or human GR increases their transactivation potential at high doses of hormone. Finally, hMRDelta5,6 is able to recruit the coactivators, steroid receptor coactivator 1, receptor interacting protein 140, and transcription intermediary factor 1alpha, which enhance its transcriptional activity. Ligand-independent transactivation and enhancement of both wild-type MR and GR activities by hMRDelta5,6 suggests that this new variant might play a role in modulating corticosteroid effects in target tissues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1586-98
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action.
pubmed:affiliation
INSERM U 478, Faculté de Médecine Xavier Bichat, 75870 Paris Cedex 18, France. zennaro@infobiogen.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't