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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2003-12-5
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pubmed:abstractText |
Interferon consensus sequence binding protein/interferon regulatory factor 8 (ICSBP/IRF-8) is a transcription factor that controls myeloid cell development. ICSBP-/- mice develop a chronic myelogenous leukemia (CML)-like syndrome. Several observations on patients and mouse models have implicated ICSBP in the pathogenesis of CML. In this paper, we investigated whether ICSBP modulates the growth-promoting activity of Bcr/Abl, the causal oncoprotein for CML. When transformed with p210 Bcr/Abl, ICSBP-/- myeloid progenitor cells lost growth factor dependence and grew in the absence of granulocyte-macrophage colony-stimulating factor. When ICSBP was ectopically expressed, Bcr/Abl-transformed cells underwent complete growth arrest and differentiated into mature, functional macrophages without inhibiting the kinase activity of Bcr/Abl. Providing a mechanistic basis for the growth arrest, ICSBP markedly repressed c-Myc messenger RNA (mRNA)-expression, a downstream target of Bcr/Abl. A further analysis with the ICSBP/estrogen receptor chimera showed that ICSBP repression of c-Myc is indirect and is mediated by another gene(s). We identified Blimp-1 and METS/PE1, potent c-Myc repressors, as direct targets of ICSBP activated in these cells. Consistent with this, ectopic Blimp-1 repressed c-Myc expression and inhibited cell growth. These results indicate that ICSBP inhibits growth of Bcr/Abl-transformed myeloid progenitor cells by activating several genes that interfere with the c-Myc pathway.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factors,
http://linkedlifedata.com/resource/pubmed/chemical/PE1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Prdm1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/imatinib,
http://linkedlifedata.com/resource/pubmed/chemical/interferon regulatory factor-8
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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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 |
15
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4547-54
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12933588-Animals,
pubmed-meshheading:12933588-Cell Differentiation,
pubmed-meshheading:12933588-Cell Division,
pubmed-meshheading:12933588-Cell Transformation, Neoplastic,
pubmed-meshheading:12933588-Cells, Cultured,
pubmed-meshheading:12933588-Enzyme Inhibitors,
pubmed-meshheading:12933588-Estradiol,
pubmed-meshheading:12933588-Fusion Proteins, bcr-abl,
pubmed-meshheading:12933588-Gene Expression Regulation,
pubmed-meshheading:12933588-Genes, myc,
pubmed-meshheading:12933588-Interferon Regulatory Factors,
pubmed-meshheading:12933588-Macrophages,
pubmed-meshheading:12933588-Mice,
pubmed-meshheading:12933588-Mice, Inbred C57BL,
pubmed-meshheading:12933588-Mice, Knockout,
pubmed-meshheading:12933588-Myeloid Cells,
pubmed-meshheading:12933588-Piperazines,
pubmed-meshheading:12933588-Pyrimidines,
pubmed-meshheading:12933588-RNA, Messenger,
pubmed-meshheading:12933588-Receptors, Estrogen,
pubmed-meshheading:12933588-Recombinant Fusion Proteins,
pubmed-meshheading:12933588-Repressor Proteins,
pubmed-meshheading:12933588-Transcription, Genetic,
pubmed-meshheading:12933588-Transcription Factors
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pubmed:year |
2003
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pubmed:articleTitle |
ICSBP/IRF-8 inhibits mitogenic activity of p210 Bcr/Abl in differentiating myeloid progenitor cells.
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pubmed:affiliation |
Bldg 6, Rm 2A01, Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Dr MSC 2753, Bethesda, MD 20892-2753, USA.
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pubmed:publicationType |
Journal Article
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