Linked Life Data

17571860

Source:http://linkedlifedata.com/resource/pubmed/id/17571860

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
27
pubmed:dateCreated
2007-7-3
pubmed:abstractText
Both agonist- and antagonist-bound glucocorticoid receptors (GRs) and progesterone receptors (PRs) regulate gene transcription with the assistance of corepressors (NCoR and SMRT) and coactivators (TIF2/GRIP1, SRC1, and AIB1). Receptor binding of these cofactors is competitive and is considered to involve interactions between the C-terminal ligand binding domain of receptors and receptor interaction domains (RIDs) in the middle and C-terminus of coactivators and corepressors, respectively. Therefore, our recent finding that an amino terminal fragment of TIF2 (TIF2.0 = amino acids 1-627) competed for GR and PR interactions with corepressors in mammalian two-hybrid assays was unexpected. Here, we use biochemical approaches (mammalian two-hybrid, pull-down, and coimmunoprecipitation assays) to locate an N-terminal GR region that is sufficient to bind TIF2.0. In contrast, an N-terminal sequence of PR-B that is largely missing in the shorter PR-A is necessary but not sufficient for TIF2.0 binding. Mutagenesis studies of NCoR establish that the more amino-terminal RID#1, but not RID#2, is necessary for binding to both GR and PR agonist and antagonist complexes. ChIP assays indicate that PR and NCoR each selectively localize to the enhancer element (PRE) of a transiently transfected PREtkLUC reporter in the presence of antagonist steroid, whereas exogenous TIF2.0 reduces the amount of PRE-associated NCoR. Importantly, exogenous TIF2.0 also inhibits the biological responses to added NCoR under the same conditions as those used in the ChIP assays. These results suggest that both N-terminal and middle sequences of TIF2 participate in competing with corepressor for regulating the gene transcriptional responses of GRs and PRs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8036-49
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Amino-terminal domain of TIF2 is involved in competing for corepressor binding to glucocorticoid and progesterone receptors.
pubmed:affiliation
Steroid Hormones Section, NIDDK/CEB, National Institutes of Health, Bethesda, Maryland 20892-1772, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural