| Accelerated degradation of PML-retinoic acid receptor alpha (PML-RARA) oncoprotein by all-trans-retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway. | |
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MedLine Citation:
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PMID: 8674046 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Acute promyelocytic leukemia (APL) is associated with a chromosomal translocation t(15;17) and successfully differentiated by all-trans-retinoic acid (ATRA) in vivo as well as in vitro. The PML-retinoic acid receptor alpha (RARA) oncoprotein, which is generated by the translocation, blocks the differentiation, and ATRA is thought to modulate the dominant negative function of PML-RARA. However, the molecular effect of ATRA on PML-RARA is unknown. In this study, we showed by means of immunoblotting that the expression of PML-RARA decreased within 12 h in APL cells treated with ATRA at concentrations greater than 0.1 microM. The decrease of PML-RARA was associated with restoration of the normal subcellular PML localization. PML-RARA transcripts were not down-regulated by ATRA. However, lactacystin, a specific inhibitor of the proteasome, almost completely inhibited the decrease of PML-RARA. These data indicate that the PML-RARA degradation is accelerated by pharmacological concentrations of ATRA, suggesting that ATRA allows APL cells to differentiate by relieving the differentiation block. |
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Authors:
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H Yoshida; K Kitamura; K Tanaka; S Omura; T Miyazaki; T Hachiya; R Ohno; T Naoe |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer research Volume: 56 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1996 Jul |
Date Detail:
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Created Date: 1996-08-12 Completed Date: 1996-08-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2945-8 Citation Subset: IM |
Affiliation:
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Department of Medicine, Nagoya University Branch Hospital, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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analogs & derivatives,
pharmacology Animals Antibodies Cell Differentiation / drug effects Cysteine Endopeptidases / metabolism* Cysteine Proteinase Inhibitors / pharmacology Drug Stability Humans Immunoblotting Leukemia, Promyelocytic, Acute / drug therapy*, metabolism* Neoplasm Proteins / drug effects*, metabolism* Nuclear Proteins* Oncogene Proteins, Fusion / drug effects*, metabolism* Rabbits Receptors, Retinoic Acid / biosynthesis Transcription Factors / biosynthesis Tretinoin / pharmacology* Tumor Cells, Cultured / drug effects Tumor Suppressor Proteins |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Cysteine Proteinase Inhibitors; 0/Neoplasm Proteins; 0/Nuclear Proteins; 0/Oncogene Proteins, Fusion; 0/Receptors, Retinoic Acid; 0/Transcription Factors; 0/Tumor Suppressor Proteins; 0/promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; 0/retinoic acid receptor alpha; 133343-34-7/lactacystin; 143220-95-5/PML protein, human; 302-79-4/Tretinoin; 616-91-1/Acetylcysteine; EC 3.4.22.-/Cysteine Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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