Simultaneous Inhibition of mTOR-Containing Complex 1 (mTORC1) and MNK Induces Apoptosis of Cutaneous T-Cell Lymphoma (CTCL) Cells 英文参考文献.docVIP

下载本文档

5
0
约2.7万字
约 8页
2017-05-13 发布于上海
举报
版权申诉

Simultaneous Inhibition of mTOR-Containing Complex 1 (mTORC1) and MNK Induces Apoptosis of Cutaneous T-Cell Lymphoma (CTCL) 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

Simultaneous Inhibition of mTOR-Containing Complex 1 (mTORC1) and MNK Induces Apoptosis of Cutaneous T-Cell Lymphoma (CTCL) Cells 英文参考文献

SimultaneousInhibitionofmTOR-ContainingComplex1 (mTORC1)andMNKInducesApoptosisofCutaneousT- CellLymphoma(CTCL)Cells MichalMarzec1,XiaobinLiu1,MariaWysocka2,AlainH.Rook2,NielsOdum3,MariuszA.Wasik1* 1Department ofPathology andLaboratoryMedicine,UniversityofPennsylvania, Philadelphia,Pennsylvania, UnitedStates ofAmerica, 2Department ofDermatology, UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesofAmerica,3InstituteofMolecularBiology,UniversityofCopenhagen,Copenhagen,Denmark Abstract Background:mTORkinaseformsthemTORC1complexbyassociatingwithraptorandotherproteinsandaffectsanumber of key cell functions. mTORC1 activates p70S6kinase 1 (p70S6K1) and inhibits 4E-binding protein 1 (4E-BP1). In turn, p70S6K1phosphorylatesaS6proteinofthe40Sribosomalsubunit(S6rp)and4E-BP1,withthelatternegativelyregulating eukaryoticinitiationfactor4E(eIF-4E).MNK1andMNK2kinasesphosphorylateandaugmentactivityofeIF4E.Rapamycin anditsanalogsarehighlyspecific,potent,andrelativelynon-toxicinhibitorsofmTORC1.AlthoughmTORC1activationis presentinmanytypesofmalignancies,rapamycin-typeinhibitorsshowsrelativelylimitedclinicalefficacyassingleagents. Initiallyusuallyindolent,CTCLdisplaysatendencytoprogresstotheaggressiveformswithlimitedresponsetotherapyand poorprognosis.Ourpreviousstudy(M.Marzecetal.2008)hasdemonstratedthatCTCLcellsdisplaymTORC1activationand short-termtreatmentofCTCL-derivedcellswithrapamycinsuppressedtheirproliferationandhadlittleeffectonthecell survival. Methods: Cells derived from CTCL were treated with mTORC1 inhibitor rapamycin and MNK inhibitor and evaluated for inhibitionofthemTORC1signalingpathwayandcellgrowthandsurvival. Results:WhereasthetreatmentwithrapamycinpersistentlyinhibitedmTORC1signaling,itsuppressedonlypartiallythecell growth. MNK kinase mediated the eIF4E phosphorylation and inhibition or depletion of MNK markedly suppressed proliferationoftheCTCLcellswhencombinedwiththerapamycin-mediatedinhibitionofmTORC1.WhileMNKinhibition alonemildlysuppressedtheCT