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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2002-12-23
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pubmed:abstractText |
Thirty percent of acute myeloid leukemia cases express a Core Binding Factor (CBF) oncoprotein or harbor point mutations in one or both AML1 (RUNX1) genes. Each of these alterations reduces endogenous CBF activities. CBFbeta-SMMHC is expressed from the inv(16) chromosome in 8% of AML cases and inhibits endogenous CBF DNA-binding. Inhibition of CBF reduces Retinoblastoma protein phosphorylation and slows the G(1) to S cell cycle transition. c-Myc, a protein which stimulates S phase entry, is over-expressed in one-third of AMLs. We have developed Ba/F3 cell lines in which zinc regulates CBFbeta-SMMHC expression and 4-hydroxytamoxifen activates c-Myc-ER. In these lines, c-Myc-ER overcomes inhibition of cell cycle progression mediated by CBFbeta-SMMHC. CBFbeta-SMMHC does not affect endogenous c-Myc RNA levels, indicating that CBF does not regulate the c-Myc gene. Conversely, c-Myc-ER does not alter CBF DNA-binding activity. Thus, c-Myc-ER acts downstream of CBFbeta-SMMHC to stimulate cell cycle progression. In a subset of CBF leukemias, elevated expression of c-Myc is expected to facilitate the proliferation of the leukemic blasts and thereby potentiate the ability of CBF oncoproteins to block differentiation.
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pubmed:grant |
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxytamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myosin Heavy Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Smooth Muscle Myosins,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-2,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Zinc
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pubmed:status |
MEDLINE
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pubmed:issn |
1538-4047
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
1
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
492-6
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12496475-Animals,
pubmed-meshheading:12496475-Cell Cycle,
pubmed-meshheading:12496475-Cell Line,
pubmed-meshheading:12496475-DNA-Binding Proteins,
pubmed-meshheading:12496475-G1 Phase,
pubmed-meshheading:12496475-Gene Expression Regulation,
pubmed-meshheading:12496475-Humans,
pubmed-meshheading:12496475-Leukemia, Myeloid,
pubmed-meshheading:12496475-Mice,
pubmed-meshheading:12496475-Myosin Heavy Chains,
pubmed-meshheading:12496475-Oncogene Proteins, Fusion,
pubmed-meshheading:12496475-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:12496475-Receptors, Estrogen,
pubmed-meshheading:12496475-S Phase,
pubmed-meshheading:12496475-Smooth Muscle Myosins,
pubmed-meshheading:12496475-Tamoxifen,
pubmed-meshheading:12496475-Transcription Factor AP-2,
pubmed-meshheading:12496475-Transcription Factors,
pubmed-meshheading:12496475-Zinc
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pubmed:articleTitle |
c-Myc overcomes cell cycle inhibition by CBFbeta-SMMHC, a myeloid leukemia oncoprotein.
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pubmed:affiliation |
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Baltimore, MD 21231, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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