Folliculin, the Product of the Birt-Hogg-Dube Tumor Suppressor Gene, Interacts with the Adherens Junction Protein p0071 to Regulate Cell-Cell Adhesion 英文参考文献.docVIP

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2017-05-11 发布于上海
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Folliculin, the Product of the Birt-Hogg-Dube Tumor Suppressor Gene, Interacts with the Adherens Junction Protein p0071 to Regulate Cell-Cell Adhesion 英文参考文献.doc

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Folliculin, the Product of the Birt-Hogg-Dube Tumor Suppressor Gene, Interacts with the Adherens Junction Protein p0071 to Regulate Cell-Cell Adhesion 英文参考文献

Folliculin,theProductoftheBirt-Hogg-DubeTumor SuppressorGene,InteractswiththeAdherensJunction Proteinp0071toRegulateCell-CellAdhesion DougA.Medvetz1.,DamirKhabibullin1.,VenkateshHariharan2,PatP.Ongusaha3, ElenaA.Goncharova4,TanjaSchlechter5,ThomasN.Darling6,IlseHofmann5,VeraP.Krymskaya4, JamesK.Liao3,HaydenHuang2,ElizabethP.Henske1* 1DivisionofPulmonaryandCriticalCareMedicine,DepartmentofMedicine,BrighamandWomen’sHospitalandHarvardMedicalSchool,Boston,Massachusetts,United States of America, 2Department of Biomedical Engineering, Columbia University, New York, New York, United States of America, 3Vascular Medicine Research Unit, BrighamWomen’sHospitalandHarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica,4Pulmonary,AllergyandCriticalCareDivision,Departmentof Medicine,University ofPennsylvania, Philadelphia,Pennsylvania, United States of America, 5Joint ResearchDivision VascularBiology, Medical Faculty Mannheim and German Cancer Research Center (DKFZ-ZMBH-Alliance), Mannheim, Germany, 6Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda,Maryland,UnitedStatesofAmerica Abstract Birt-Hogg-Dube (BHD) is a tumor suppressor gene syndrome associated with fibrofolliculomas, cystic lung disease, and chromophoberenalcellcarcinoma.InseekingtoelucidatethepathogenesisofBHD,wediscoveredaphysicalinteraction between folliculin (FLCN), the proteinproduct of the BHDgene, andp0071, anarmadillo repeat containing protein that localizestothecytoplasmandtoadherensjunctions.Adherensjunctionsareoneofthethreecell-celljunctionsthatare essentialtotheestablishmentandmaintenanceofthecellulararchitectureofallepithelialtissues.Surprisingly,wefound that downregulation of FLCN leads to increased cell-cell adhesion in functional cell-based assays and disruption of cell polarityinathree-dimensionallumen-formingassay,bothofwhicharephenocopiedbydownregulationofp0071.These dataindicatethattheFLCN-p0071proteincomplexisanegativeregulatorofcell-celladhesion.W