Abstract
RNA interference-mediated suppression of MYB expression promoted apoptosis in the AML cell line U937, without affecting expression of the anti-apoptotic MYB target BCL2. This was accompanied by up-regulation of the pro-apoptotic gene DRAK2 and stimulation of caspase-9 activity. Moreover, RNA interference-mediated suppression of DRAK2 in U937 cells alleviated apoptosis induced by MYB down-regulation. Finally ChIP assays showed that in U937 cells MYB binds to a conserved element upstream of the DRAK2 transcription start site. Together, these findings identify a novel mechanism by which MYB suppresses apoptosis in an AML model cell line.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis Regulatory Proteins / biosynthesis*
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Apoptosis Regulatory Proteins / genetics
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Apoptosis*
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Caspase 9 / genetics
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Caspase 9 / metabolism
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Down-Regulation / genetics
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Gene Expression Regulation, Leukemic*
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Humans
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K562 Cells
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Leukemia, Myeloid, Acute / genetics
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Leukemia, Myeloid, Acute / metabolism*
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Leukemia, Myeloid, Acute / pathology
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Oncogene Proteins v-myb / genetics
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Oncogene Proteins v-myb / metabolism*
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Protein Serine-Threonine Kinases / biosynthesis*
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Protein Serine-Threonine Kinases / genetics
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Response Elements / genetics
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Transcription, Genetic*
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U937 Cells
Substances
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Apoptosis Regulatory Proteins
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Oncogene Proteins v-myb
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Proto-Oncogene Proteins c-bcl-2
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Protein Serine-Threonine Kinases
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STK17B protein, human
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Caspase 9