Acetylation of the Proto-Oncogene EVI1 Abrogates Bcl-xL Promoter Binding and Induces Apoptosis 英文参考文献.docVIP

Acetylation of the Proto-Oncogene EVI1 Abrogates Bcl-xL Promoter Binding and Induces Apoptosis 英文参考文献.doc

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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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