| pubmed-article:19155306 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C0023467 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C0140279 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C0040845 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C1704632 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C0871261 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C1418582 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C2911692 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C1706817 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C2349975 | lld:lifeskim |
| pubmed-article:19155306 | lifeskim:mentions | umls-concept:C0297323 | lld:lifeskim |
| pubmed-article:19155306 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:19155306 | pubmed:dateCreated | 2009-1-30 | lld:pubmed |
| pubmed-article:19155306 | pubmed:abstractText | The peptidyl-prolyl-isomerase Pin1 interacts with phosphorylated proteins, altering their conformation. The retinoic acid receptor RARalpha and the acute-promyelocytic-leukemia-specific counterpart PML-RARalpha directly interact with Pin1. Overexpression of Pin1 inhibits ligand-dependent activation of RARalpha and PML-RARalpha. Inhibition is relieved by Pin1-targeted short interfering RNAs and by pharmacologic inhibition of the catalytic activity of the protein. Mutants of Pin1 catalytically inactive or defective for client-protein-binding activity are incapable of inhibiting ligand-dependent RARalpha transcriptional activity. Functional inhibition of RARalpha and PML-RARalpha by Pin1 correlates with degradation of the nuclear receptors via the proteasome-dependent pathway. In the acute myelogenous leukemia cell lines HL-60 and NB4, Pin1 interacts with RARalpha in a constitutive fashion. Suppression of Pin1 by a specific short hairpin RNA in HL-60 or NB4 cells stabilizes RARalpha and PML-RARalpha, resulting in increased sensitivity to the cytodifferentiating and antiproliferative activities of all-trans retinoic acid. Treatment of the two cell lines and freshly isolated acute myelogenous leukemia blasts (M1 to M4) with ATRA and a pharmacologic inhibitor of Pin1 causes similar effects. Our results add a further layer of complexity to the regulation of nuclear retinoic acid receptors and suggest that Pin1 represents an important target for strategies aimed at increasing the therapeutic index of retinoids. | lld:pubmed |
| pubmed-article:19155306 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19155306 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19155306 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19155306 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19155306 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19155306 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:19155306 | pubmed:issn | 1538-7445 | lld:pubmed |
| pubmed-article:19155306 | pubmed:author | pubmed-author:RambaldiAless... | lld:pubmed |
| pubmed-article:19155306 | pubmed:author | pubmed-author:Del... | lld:pubmed |
| pubmed-article:19155306 | pubmed:author | pubmed-author:RustighiAless... | lld:pubmed |
| pubmed-article:19155306 | pubmed:author | pubmed-author:GarattiniEnri... | lld:pubmed |
| pubmed-article:19155306 | pubmed:author | pubmed-author:Gianni'Mauriz... | lld:pubmed |
| pubmed-article:19155306 | pubmed:author | pubmed-author:TeraoMinekoM | lld:pubmed |
| pubmed-article:19155306 | pubmed:author | pubmed-author:Rochette-Egly... | lld:pubmed |
| pubmed-article:19155306 | pubmed:author | pubmed-author:ParrellaEdoar... | lld:pubmed |
| pubmed-article:19155306 | pubmed:author | pubmed-author:RaskaIvanIJr | lld:pubmed |
| pubmed-article:19155306 | pubmed:author | pubmed-author:BoldettiAndre... | lld:pubmed |
| pubmed-article:19155306 | pubmed:author | pubmed-author:GuarnacciaVal... | lld:pubmed |
| pubmed-article:19155306 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19155306 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:19155306 | pubmed:volume | 69 | lld:pubmed |
| pubmed-article:19155306 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19155306 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19155306 | pubmed:pagination | 1016-26 | lld:pubmed |
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| pubmed-article:19155306 | pubmed:meshHeading | pubmed-meshheading:19155306... | lld:pubmed |
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| pubmed-article:19155306 | pubmed:meshHeading | pubmed-meshheading:19155306... | lld:pubmed |
| pubmed-article:19155306 | pubmed:meshHeading | pubmed-meshheading:19155306... | lld:pubmed |
| pubmed-article:19155306 | pubmed:meshHeading | pubmed-meshheading:19155306... | lld:pubmed |
| pubmed-article:19155306 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19155306 | pubmed:articleTitle | Inhibition of the peptidyl-prolyl-isomerase Pin1 enhances the responses of acute myeloid leukemia cells to retinoic acid via stabilization of RARalpha and PML-RARalpha. | lld:pubmed |
| pubmed-article:19155306 | pubmed:affiliation | Laboratory of Molecular Biology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. egarattini@marionegri.it | lld:pubmed |
| pubmed-article:19155306 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:19155306 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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