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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2002-12-17
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pubmed:abstractText |
The transcription factor PU.1 plays a pivotal role in normal myeloid differentiation. PU.1(-/-) mice exhibit a complete block in myeloid differentiation. Heterozygous PU.1 mutations were reported in some patients with acute myeloid leukemia (AML), but not in AML with translocation t(8;21), which gives rise to the fusion gene AML1-ETO. Here we report a negative functional impact of AML1-ETO on the transcriptional activity of PU.1. AML1-ETO physically binds to PU.1 in t(8;21)(+) Kasumi-1 cells. AML1-ETO binds to the beta(3)beta(4) region in the DNA-binding domain of PU.1 and displaces the coactivator c-Jun from PU.1, thus down-regulating the transcriptional activity of PU.1. This physical interaction of AML1-ETO and PU.1 did not abolish the DNA-binding capacity of PU.1. AML1-ETO down-regulates the transactivation capacity of PU.1 in myeloid U937 cells, and the expression levels of PU.1 target genes in AML French-American-British (FAB) subtype M2 patients with t(8;21) were lower than in patients without t(8;21). Conditional expression of AML1-ETO causes proliferation in mouse bone marrow cells and inhibits antiproliferative function of PU.1. Overexpression of PU.1, however, differentiates AML1-ETO-expressing Kasumi-1 cells to the monocytic lineage. Thus, the function of PU.1 is down-regulated by AML1-ETO in t(8;21) myeloid leukemia, whereas overexpression of PU.1 restores normal differentiation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
270-7
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12393465-Animals,
pubmed-meshheading:12393465-Binding Sites,
pubmed-meshheading:12393465-Bone Marrow Cells,
pubmed-meshheading:12393465-Cell Differentiation,
pubmed-meshheading:12393465-Cell Division,
pubmed-meshheading:12393465-Chromosomes, Human, Pair 21,
pubmed-meshheading:12393465-Chromosomes, Human, Pair 8,
pubmed-meshheading:12393465-Core Binding Factor Alpha 2 Subunit,
pubmed-meshheading:12393465-Down-Regulation,
pubmed-meshheading:12393465-Humans,
pubmed-meshheading:12393465-Leukemia, Myeloid, Acute,
pubmed-meshheading:12393465-Mice,
pubmed-meshheading:12393465-Oncogene Proteins, Fusion,
pubmed-meshheading:12393465-Protein Binding,
pubmed-meshheading:12393465-Proto-Oncogene Proteins,
pubmed-meshheading:12393465-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:12393465-Trans-Activators,
pubmed-meshheading:12393465-Transcription, Genetic,
pubmed-meshheading:12393465-Transcription Factors,
pubmed-meshheading:12393465-Translocation, Genetic,
pubmed-meshheading:12393465-Tumor Cells, Cultured
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pubmed:year |
2003
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pubmed:articleTitle |
The myeloid master regulator transcription factor PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia.
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pubmed:affiliation |
Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University Munich and GSF-National Research Center for Environment and Health, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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