Oncogenic Kit Triggers Shp2Erk12 Pathway to Down-Regulate the Pro-Apoptotic Protein Bim and to Promote Apoptosis Resistance in Leukemic Cells 英文参考文献.docVIP

下载本文档

5
0
约3.31万字
约 7页
2017-05-12 发布于上海
举报
版权申诉

Oncogenic Kit Triggers Shp2Erk12 Pathway to Down-Regulate the Pro-Apoptotic Protein Bim and to Promote Apoptosis Resistance in Leukemic Cells 英文参考文献.doc

1、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。。
2、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
3、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
4、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
5、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
6、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
7、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Oncogenic Kit Triggers Shp2Erk12 Pathway to Down-Regulate the Pro-Apoptotic Protein Bim and to Promote Apoptosis Resistance in Leukemic Cells 英文参考文献

OncogenicKitTriggersShp2/Erk1/2PathwaytoDown- RegulatethePro-ApoptoticProteinBimandtoPromote ApoptosisResistanceinLeukemicCells Dorothe′eSelimoglu-Buet,IsabelleGallais,NicoleDenis,ChristelGuillouf,Franc?oiseMoreau-Gachelin* InstitutCurie,Inserm-U830,Paris,France Abstract Oncogenic mutations leading to persistent kinase activities are implicated in various human malignancies. Thereby, signalingpathway-targetedtherapiesarepowerfulcustomizedtreatmenttoeradicatecancercells.Inmurineandhuman leukemia cells harboring mutations in Kit, we previously showed that distinct and independent pathways controlled resistance to apoptosis or cell cycle. A treatment with PI3Kinase inhibitors to reduce cell proliferation combined with inhibitorsofErk1/2activitytopromoteapoptosishadsynergisticeffectsallowingeradicationofleukemiacellgrowth.We reportedherethatBimEL,apro-apoptoticmemberoftheBcl2familyproteins,isthetargetofErk1/2signalingandthatits down-regulationisresponsiblefortheapoptosisresistanceofmurineandhumanleukemiccells.DownstreamofKitmutant, thetyrosinephosphataseShp2maintainsBimELexpressionatalowlevel,throughErk/2activationandproteosomalBimEL degradation. This process is controlled by Shp2 independently of other signaling pathways activated downstream of oncogenicKit,demonstratingthatShp2isakeyregulatorofBimexpressioninthecontextofanoncogenicsignaling.The increaseinBimELexpressionisassociatedtoanincreasedapoptosis.Moreover,thedepletionofBimovercomesapoptosis associatedwithErk1/2inactivationinUO126-treatedleukemiccells,therebyestablishingthecontributionofBimtodrug- inducedapoptosis.ThesedataprovideamolecularrationaleforusingBH3mimeticsincombinationwithPI3Kinhibitorsto treatleukemia,especiallyinthecaseofanoncogenicsignalingrefractorytoTyrosineKinaseinhibitors. Citation: Selimoglu-Buet D, Gallais I, Denis N, Guillouf C, Moreau-Gachelin F (2012) Oncogenic Kit Triggers Shp2/Erk1/2 Pathway to Down-Regulate the Pro- ApoptoticProteinBimandtoPromoteApoptosisResistanceinLeukemicCells.PL