| pubmed-article:12496475 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12496475 | lifeskim:mentions | umls-concept:C0086661 | lld:lifeskim |
| pubmed-article:12496475 | lifeskim:mentions | umls-concept:C0023470 | lld:lifeskim |
| pubmed-article:12496475 | lifeskim:mentions | umls-concept:C0029005 | lld:lifeskim |
| pubmed-article:12496475 | lifeskim:mentions | umls-concept:C1516332 | lld:lifeskim |
| pubmed-article:12496475 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:12496475 | pubmed:dateCreated | 2002-12-23 | lld:pubmed |
| pubmed-article:12496475 | 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. | lld:pubmed |
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| pubmed-article:12496475 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:12496475 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:12496475 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12496475 | pubmed:issn | 1538-4047 | lld:pubmed |
| pubmed-article:12496475 | pubmed:author | pubmed-author:YangYandanY | lld:pubmed |
| pubmed-article:12496475 | pubmed:author | pubmed-author:CivinCurt ICI | lld:pubmed |
| pubmed-article:12496475 | pubmed:author | pubmed-author:FriedmanAlan... | lld:pubmed |
| pubmed-article:12496475 | pubmed:author | pubmed-author:BernardinFlor... | lld:pubmed |
| pubmed-article:12496475 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12496475 | pubmed:volume | 1 | lld:pubmed |
| pubmed-article:12496475 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12496475 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12496475 | pubmed:pagination | 492-6 | lld:pubmed |
| pubmed-article:12496475 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
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| pubmed-article:12496475 | pubmed:articleTitle | c-Myc overcomes cell cycle inhibition by CBFbeta-SMMHC, a myeloid leukemia oncoprotein. | lld:pubmed |
| pubmed-article:12496475 | pubmed:affiliation | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Baltimore, MD 21231, USA. | lld:pubmed |
| pubmed-article:12496475 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12496475 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:12496475 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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