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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2000-10-18
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pubmed:abstractText |
In many hematopoietic malignancies, c-Myb, a nuclear transcription factor of hematopoietic cells, is an activated oncogene. To achieve a specific inhibition of hematopoietic tumor growth, an inducible fusion protein consisting of the Myb DNA binding domain (DBD) and the active repressor domain KRAB, the Krüppel-associated box of the developmental zinc-finger protein KOX-1, was generated. The MybDBD-KRAB fusion protein is a potent repressor of Myb-induced gene expression from Myb-responsive reporter genes containing several Myb binding sites. MybDBD-KRAB expressed in the human hematopoietic promyelocytic cell line HL60 significantly reduces cell proliferation by inducing apoptosis. Expression of MybDBD-KRAB in subcutaneously injected HL60 cells leads to inhibition of tumor formation in nude mice. The MybDBD-KRAB effect is specific to cell lines expressing c-Myb. It is conceivable to fuse the KRAB domain to other DBDs of oncogenic transcription factors and target them to their respective DNA response elements to selectively drive tumor cells into apoptosis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0929-1903
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
963-72
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10880029-Animals,
pubmed-meshheading:10880029-Apoptosis,
pubmed-meshheading:10880029-Blotting, Western,
pubmed-meshheading:10880029-Cell Division,
pubmed-meshheading:10880029-DNA-Binding Proteins,
pubmed-meshheading:10880029-Flow Cytometry,
pubmed-meshheading:10880029-Fluorescent Antibody Technique,
pubmed-meshheading:10880029-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:10880029-Genes, myb,
pubmed-meshheading:10880029-Genetic Vectors,
pubmed-meshheading:10880029-HL-60 Cells,
pubmed-meshheading:10880029-Hematopoietic Stem Cells,
pubmed-meshheading:10880029-Humans,
pubmed-meshheading:10880029-Injections, Subcutaneous,
pubmed-meshheading:10880029-Mice,
pubmed-meshheading:10880029-Mice, Nude,
pubmed-meshheading:10880029-Microscopy, Confocal,
pubmed-meshheading:10880029-Neoplasm Transplantation,
pubmed-meshheading:10880029-Neoplasms,
pubmed-meshheading:10880029-Precipitin Tests,
pubmed-meshheading:10880029-Promoter Regions, Genetic,
pubmed-meshheading:10880029-Proto-Oncogene Proteins,
pubmed-meshheading:10880029-Repressor Proteins,
pubmed-meshheading:10880029-Transcription, Genetic,
pubmed-meshheading:10880029-Transfection,
pubmed-meshheading:10880029-Tumor Stem Cell Assay,
pubmed-meshheading:10880029-Zinc Fingers
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pubmed:year |
2000
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pubmed:articleTitle |
Inhibition of human hematopoietic tumor formation by targeting a repressor Myb-KRAB to DNA.
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pubmed:affiliation |
Institute of Medical Virology, University of Zurich, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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