Linked Life Data

15319284

Source:http://linkedlifedata.com/resource/pubmed/id/15319284

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2004-12-6
pubmed:abstractText
Nuclear receptors are ligand-modulated transcription factors regulated by interactions with corepressors and coactivators, whose functions are not fully understood. Acute promyelocytic leukemia (APL) is characterized by a translocation, t(15;17), that produces a PML/RARalpha fusion oncoprotein, whose abnormal transcriptional function is successfully targeted by pharmacologic levels of all-trans-retinoic acid (ATRA). Mutations in the ligand-binding domain of PML/RARalpha that confer resistance to ATRA have been studied by expression in nonhematopoietic cells, such as Cos-1. Here, we show that ATRA binding and transcriptional activation by the same PML/RARalpha mutant differ markedly between nonhematopoietic and leukemic cell lines. Differential expression of the corepressor isoform silencing mediator for retinoid and thyroid receptors beta (SMRTbeta) correlates with increased ligand binding and transcription by the mutant PML/RARalpha. Transient and stable overexpression of SMRTbeta in hematopoietic cells that only express SMRTalpha increased ATRA binding, ligand-induced transcription, and ATRA-induced cell differentiation. This effect may not be limited to abnormal nuclear receptors, because overexpression of SMRTbeta increased ATRA-induced binding and transcriptional activation of wild-type receptors PML/RARalpha and RARalpha. Our results suggest a novel role for the SMRTbeta isoform whereby its cell-specific expression may influence the binding and transcriptional capacities of nuclear receptors, thus providing new evidence of distinct functions of corepressor isoforms and adding complexity to transcriptional regulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4226-35
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15319284-Cell Line, Tumor, pubmed-meshheading:15319284-Chromosomes, Human, Pair 15, pubmed-meshheading:15319284-Chromosomes, Human, Pair 17, pubmed-meshheading:15319284-DNA-Binding Proteins, pubmed-meshheading:15319284-Drug Resistance, Neoplasm, pubmed-meshheading:15319284-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15319284-Humans, pubmed-meshheading:15319284-Jurkat Cells, pubmed-meshheading:15319284-Leukemia, Promyelocytic, Acute, pubmed-meshheading:15319284-Ligands, pubmed-meshheading:15319284-Neoplasm Proteins, pubmed-meshheading:15319284-Nuclear Receptor Co-Repressor 2, pubmed-meshheading:15319284-Oncogene Proteins, Fusion, pubmed-meshheading:15319284-Plasmids, pubmed-meshheading:15319284-Receptors, Retinoic Acid, pubmed-meshheading:15319284-Repressor Proteins, pubmed-meshheading:15319284-Transcriptional Activation, pubmed-meshheading:15319284-Translocation, Genetic, pubmed-meshheading:15319284-Tretinoin
pubmed:year
2004
pubmed:articleTitle
Expression of SMRTbeta promotes ligand-induced activation of mutated and wild-type retinoid receptors.
pubmed:affiliation
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 3755, Chemin de la Côte Ste-Catherine, Montreal, Quebec, Canada H3T 1E2.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't