Akt1 Intramitochondrial Cycling Is a Crucial Step in the Redox Modulation of Cell Cycle Progression 英文参考文献.docVIP

下载本文档

0
0
约5.71万字
约 13页
2017-05-11 发布于上海
举报
版权申诉

Akt1 Intramitochondrial Cycling Is a Crucial Step in the Redox Modulation of Cell Cycle Progression 英文参考文献.doc

1、本文档共13页，可阅读全部内容。
2、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。
3、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。
4、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)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、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。
7、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。
8、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

Akt1 Intramitochondrial Cycling Is a Crucial Step in the Redox Modulation of Cell Cycle Progression 英文参考文献

Akt1IntramitochondrialCyclingIsaCrucialStepinthe RedoxModulationofCellCycleProgression ValeriaGabrielaAnticoArciuch1*,SoledadGalli2,Mar?′aClaraFranco3,PhilipY.Lam4,EnriqueCadenas4, Mar?′aCeciliaCarreras1,5,JuanJose′ Poderoso1* 1LaboratoryofOxygenMetabolism,UniversityHospital,UniversityofBuenosAires,BuenosAires,Argentina,2DepartmentofOrganicChemistry,FacultyofExactand NaturalSciences,UniversityofBuenosAires,BuenosAires,Argentina,3LaboratoryofMotorNeuronBiology,BurkeMedicalResearchInstitute,UniversityofCornell,New York, New York, United States of America, 4Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles,California,UnitedStatesofAmerica,5DepartmentofClinicalBiochemistry,UniversityHospital,SchoolofPharmacyandBiochemistry,UniversityofBuenosAires, BuenosAires,Argentina Abstract Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activatedbygrowthfactorsandoxidativestressbysequentialphosphorylationofSer473bymTORC2andThr308 byPDK1. Onthesebases,weinvestigatedthemechanisticconnectionofH2O2yield,mitochondrialactivationofAkt1andcellcycle progressioninNIH/3T3celllinewithconfocalmicroscopy,invivoimaging,anddirectedmutagenesis.Wedemonstratethat modulationbyH2O2entailstheentranceofcytosolicP-Akt1Ser473 tomitochondria,whereitisfurtherphosphorylatedat Thr308 by constitutive PDK1. Phosphorylation of Thr308 in mitochondria determines Akt1 passage to nuclei and triggers genomicpost-translationalmechanismsforcellproliferation.AthighH2O2,Akt1-PDK1associationisdisruptedandP-Akt1 Ser473 accumulates in mitochondria in detriment to nuclear translocation; accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases cytochrome c release to cytosol leading to apoptosis. As assessed by mass spectra,differentialH2O2effectsonAkt1-PDKinteractiondependontheselectiveoxidationofCys310tosulfenicorcysteic acids.Theseresultsin