Linked Life Data

17475621

Source:http://linkedlifedata.com/resource/pubmed/id/17475621

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2007-6-18
pubmed:abstractText
The aberrant association of promyelocytic leukemia protein-retinoic acid receptor-alpha (PML-RARalpha) with corepressor complexes is generally thought to contribute to the ability of PML-RARalpha to regulate transcription. We report here that PML-RARalpha acquires aberrant association with coactivators. We show that endogenous PML-RARalpha interacts with the histone acetyltransferases CBP, p300, and SRC-1 in a hormoneindependent manner, an association not seen for RARalpha. This hormone-independent coactivator binding activity requires an intact ligand-binding domain and the NR box of the coactivators. Confocal microscopy studies demonstrate that exogenous PML-RARalpha sequesters and colocalizes with coactivators. These observations correlate with the ability of PML-RARalpha to attenuate the transcription activation of the Notch signaling downstream effector, CBF1, and of the glucocorticoid receptor. This includes attenuation of the glucocorticoid-induced leucine zipper (GILZ) and FLJ25390 target genes of the endogenous glucocorticoid receptor. Furthermore, treatment of NB4 cells with all-trans-retinoic acid, which promotes PML-RARalpha degradation, resulted in increased activation of GILZ. On the basis of these findings, we propose a model in which the hormone-independent association between PML-RARalpha and coactivators contributes to its ability to regulate gene expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18584-96
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17475621-Animals, pubmed-meshheading:17475621-Cell Line, pubmed-meshheading:17475621-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17475621-Glutathione Transferase, pubmed-meshheading:17475621-HL-60 Cells, pubmed-meshheading:17475621-Humans, pubmed-meshheading:17475621-Microscopy, Fluorescence, pubmed-meshheading:17475621-Models, Biological, pubmed-meshheading:17475621-Neoplasm Proteins, pubmed-meshheading:17475621-Nuclear Proteins, pubmed-meshheading:17475621-Plasmids, pubmed-meshheading:17475621-Protein Binding, pubmed-meshheading:17475621-Protein Structure, Tertiary, pubmed-meshheading:17475621-Receptors, Notch, pubmed-meshheading:17475621-Receptors, Retinoic Acid, pubmed-meshheading:17475621-Signal Transduction, pubmed-meshheading:17475621-Transcription Factors, pubmed-meshheading:17475621-Tumor Suppressor Proteins
pubmed:year
2007
pubmed:articleTitle
Aberrant association of promyelocytic leukemia protein-retinoic acid receptor-alpha with coactivators contributes to its ability to regulate gene expression.
pubmed:affiliation
Department of Biochemistry, School of Medicine, Case Western Reserve University, and the Research Institute of University Hospitals of Cleveland, OH 44106, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural