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rdf:type |
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lifeskim:mentions |
umls-concept:C0017337,
umls-concept:C0029005,
umls-concept:C0079904,
umls-concept:C0086860,
umls-concept:C0205101,
umls-concept:C0205102,
umls-concept:C0376515,
umls-concept:C0429403,
umls-concept:C0439851,
umls-concept:C0851285,
umls-concept:C1145667,
umls-concept:C1167622,
umls-concept:C1413357,
umls-concept:C1417708,
umls-concept:C1423613,
umls-concept:C1516044,
umls-concept:C1539081,
umls-concept:C1552596,
umls-concept:C1704259,
umls-concept:C1704675,
umls-concept:C1705525,
umls-concept:C1705987,
umls-concept:C1947931,
umls-concept:C2349209,
umls-concept:C2825311
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pubmed:issue |
2
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pubmed:dateCreated |
2009-2-11
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pubmed:abstractText |
CCAAT/enhancer-binding protein alpha (C/EBPalpha) is mutated in 10% of acute myeloid leukemias, resulting in either a truncated protein or an altered leucine zipper (C/EBPalphaLZ) that prevents DNA binding. C/EBPalpha induces bcl-2 in cooperation with nuclear factor-kappaB (NF-kappaB) p50 to inhibit apoptosis. We now demonstrate that C/EBPalpha or a C/EBPalphaLZ oncoprotein binds the bcl-2 P2 promoter in chromatin immunoprecipitation assays and induces the promoter dependent on the integrity of a kappaB site. C/EBPalpha expressed as a transgene in B cells binds and activates the bcl-2 promoter, but not in nfkb1-/- mice lacking NF-kappaB p50. Bcl-2 is central to the intrinsic apoptotic pathway, whereas FLICE inhibitory protein (FLIP) modulates caspase-8, the initiator caspase of the extrinsic pathway. C/EBPalpha and C/EBPalphaLZ also bind the FLIP promoter and induce its expression dependent upon NF-kappaB p50. Moreover, induction of FLIP by C/EBPalpha protects splenocytes from Fas ligand-induced apoptosis, but only if p50 is present. We also demonstrate the direct interaction between bacterially produced C/EBPalpha and NF-kappaB p50, mediated by the C/EBPalpha basic region. These findings indicate that C/EBPalpha or its oncoproteins activate the bcl-2 and FLIP genes by tethering to their promoters through bound NF-kappaB p50. Targeting their interaction may favor apoptosis of transformed cells.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18987666-10748205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18987666-11242107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18987666-11283671,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18987666-8413306,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18987666-8746564,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18987666-8756629,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18987666-9414177
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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 |
Feb
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pubmed:issn |
1476-5551
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
365-74
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
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pubmed:year |
2009
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pubmed:articleTitle |
C/EBPalpha or C/EBPalpha oncoproteins regulate the intrinsic and extrinsic apoptotic pathways by direct interaction with NF-kappaB p50 bound to the bcl-2 and FLIP gene promoters.
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pubmed:affiliation |
Division of Pediatric Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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