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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2010-1-11
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pubmed:abstractText |
The E2A-HLF fusion transcription factor generated by t(17;19)(q22;p13) translocation is found in a small subset of pro-B cell acute lymphoblastic leukemias (ALLs) and promotes leukemogenesis by substituting for the antiapoptotic function of cytokines. Here we show that t(17;19)+ ALL cells express Survivin at high levels and that a dominant negative mutant of E2A-HLF suppresses Survivin expression. Forced expression of E2A-HLF in t(17;19)(-) leukemia cells up-regulated Survivin expression, suggesting that Survivin is a downstream target of E2A-HLF. Analysis using a counterflow centrifugal elutriator revealed that t(17;19)+ ALL cells express Survivin throughout the cell cycle. Reporter assays revealed that E2A-HLF induces survivin expression at the transcriptional level likely through indirect down-regulation of a cell cycle-dependent cis element in the promoter region. Down-regulation of Survivin function by a dominant negative mutant of Survivin or reduction of Survivin expression induced massive apoptosis throughout the cell cycle in t(17;19)+ cells mainly through caspase-independent pathways involving translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus. AIF knockdown conferred resistance to apoptosis caused by down-regulation of Survivin function. These data indicated that reversal of AIF translocation by Survivin, which is induced by E2A-HLF throughout the cell cycle, is one of the key mechanisms in the protection of t(17;19)+ leukemia cells from apoptosis.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-10082541,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-10518212,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-10518215,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-10567210,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-11604477,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-12114629,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-12509766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-12590264,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-9122243,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-9256286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-9742120,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-9850056,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-9859993,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-9864177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-9989411,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887369-9990045
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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/BIRC5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Basic-Leucine Zipper Transcription...,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/HLF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TCF3 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1083-351X
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pubmed:author |
pubmed-author:AkiDaisukeD,
pubmed-author:AlturaRachel ARA,
pubmed-author:ArisakaOsamuO,
pubmed-author:FurukawaYusukeY,
pubmed-author:GotoHiroakiH,
pubmed-author:InabaToshiyaT,
pubmed-author:InukaiTakeshiT,
pubmed-author:KikuchiJiroJ,
pubmed-author:KurosawaHidemitsuH,
pubmed-author:LookA ThomasAT,
pubmed-author:MatsuiHirotakaH,
pubmed-author:MatsunagaTakayukiT,
pubmed-author:OkuyaMayukoM,
pubmed-author:SugitaKenichK
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
285
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1850-60
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19887369-Humans,
pubmed-meshheading:19887369-Animals,
pubmed-meshheading:19887369-Mice,
pubmed-meshheading:19887369-Mutation,
pubmed-meshheading:19887369-Base Sequence,
pubmed-meshheading:19887369-Cell Survival,
pubmed-meshheading:19887369-Molecular Sequence Data,
pubmed-meshheading:19887369-Translocation, Genetic,
pubmed-meshheading:19887369-Cell Cycle,
pubmed-meshheading:19887369-Cell Line, Tumor
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