Acetylation of the Proto-Oncogene EVI1 Abrogates Bcl-xL Promoter Binding and Induces Apoptosis 英文参考文献.docVIP
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Acetylation of the Proto-Oncogene EVI1 Abrogates Bcl-xL Promoter Binding and Induces Apoptosis 英文参考文献
AcetylationoftheProto-OncogeneEVI1AbrogatesBcl-
xLPromoterBindingandInducesApoptosis
AnjanKumarPradhan1,AlokDasMohapatra2,KasturiBalaNayak1,SoumenChakraborty1*
1Department of Gene Function and Regulation, Institute of Life Sciences, Bhubaneswar, Orissa, India, 2Department of Infectious Disease Biology, Institute of Life
Sciences,Bhubaneswar,Orissa,India
Abstract
EVI1(EcotropicViralIntegrationsiteI),whichwasoriginallyidentifiedasamyeloidtransforminggenebymeansofretroviral
insertionalmutagenesisinmouseleukemia,encodesanuclearDNAbindingzincfingerprotein.Thepresenceofzincfingers
thatareabletobindtospecificsequencesofDNAsuggeststhatEVI1isatranscriptionalregulator;however,exceptafew,
targetgenesofEVI1arepoorlyfunctionallyidentifiedthusfar.InthisstudyweprovideevidencethatEVI1directlyinduces
theexpressionofBcl-xLthroughthefirstsetofzincfingerandtherebyinhibitsapoptosis.ChIPanalysisshowedthatEVI1
binds to the Bcl-xL promoter in HT-29 cells, a colon carcinoma cell line, which expresses EVI1. The observation is also
supported by the fact that EVI1 siRNA treated HT-29 cells, shows a down regulation of Bcl-xL expression and that over
expressionofEVI1resultsintheinductionoftheBcl-xLreporterconstruct.AsetofEVI1positivechronicmyeloidleukemia
(CML)samplesalsoshowedhigherBcl-xLexpressionwithrespecttoEVI1negativesamples.Interestingly,co-expressionof
EVI1withwildtype,butnotwithdominant-negativeformofPCAF,abolishestheeffectofEVI1onBcl-xL,indicatingthat
acetylationofEVI1abrogatesitsabilitynotonlytobindBcl-xLpromoterbutalsoalleviateBcl-xLactivity.Finallywehave
shownthatEVI1expressionregulatesapoptosisinHT-29cells,whichisabrogatedwhenHT-29cellsaretransfectedwith
EVI1siRNAorPCAF.TheresultforthefirsttimeshowsadirectpathwaybywhichEVI1canprotectcellsfromapoptosisand
alsodemonstratesthatthepathwaycanbereversedwhenEVI1isacetylated.
Citation:PradhanAK,MohapatraAD,NayakKB,ChakrabortyS(2011)AcetylationoftheProto-OncogeneEVI1AbrogatesBcl-xLPromoterBindingandInduces
Apoptosis.PLoSONE6(9):e25370.doi
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