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dc.contributor.author김철근-
dc.date.accessioned2017-03-21T01:07:41Z-
dc.date.available2017-03-21T01:07:41Z-
dc.date.issued2015-07-
dc.identifier.citationCELL DEATH AND DIFFERENTIATION, v. 22, no. 4, Page. 665-676en_US
dc.identifier.issn1350-9047-
dc.identifier.issn1476-5403-
dc.identifier.urihttp://www.nature.com/cdd/journal/v22/n4/abs/cdd2014155a.html-
dc.identifier.urihttp://hdl.handle.net/20.500.11754/26230-
dc.description.abstractCytokeratin19 (KRT19) is widely used as a biomarker for the detection of disseminated tumors. Using an LC-MS/MS proteomics approach, we found that KRT19 was upregulated in HER2-overexpressing cells and tissues. KRT19 expression was induced by HER2-downstream ERK at the transcriptional level. Another HER2-downstream kinase, Akt, was found to phosphorylate KRT19 on Ser35 and induce membrane translocation of KRT19 and remodeling of KRT19 from filamentous to granulous form. KRT19 phosphorylated by Akt could bind HER2 on the plasma membrane and stabilized HER2 via inhibition of proteasome-mediated degradation of HER2. Silencing of KRT19 by shRNA resulted in increased ubiquitination and destabilization of HER2. Moreover, treatment of KRT19 antibody resulted in downregulation of HER2 and reduced cell viability. These data provide a new rationale for targeting HER2-positive breast cancers.en_US
dc.description.sponsorshipThis work was supported by NRF grant (2013-059143) from the Korea Research Foundation and the Converging Research Center Program funded by Ministry of Science, ICT & Future Planning (Project No. 2014048814). We thank Dr. Omary (Stanford University), Dr. Rustgi (Univ of Pennsylvania) and Dr. Su-Jae Lee for the plasmid constructs.en_US
dc.language.isoenen_US
dc.publisherNATURE PUBLISHING GROUPen_US
dc.subjectPHYSIOLOGICAL PHOSPHORYLATION SITEen_US
dc.subjectINTERMEDIATE-FILAMENT PROTEINen_US
dc.subjectEPIDERMAL-GROWTH-FACTORen_US
dc.subjectBREAST-CANCER CELLSen_US
dc.subjectRNA-POSITIVE CELLSen_US
dc.subjectTUMOR-CELLSen_US
dc.subjectGENE-TRANSCRIPTIONen_US
dc.subjectPERIPHERAL-BLOODen_US
dc.subjectKERATIN 19en_US
dc.subjectKINASEen_US
dc.titleCytokeratin19 induced by HER2/ERK binds and stabilizes HER2 on cell membranesen_US
dc.typeArticleen_US
dc.relation.volume22-
dc.identifier.doi10.1038/cdd.2014.155-
dc.relation.page665-676-
dc.relation.journalCELL DEATH AND DIFFERENTIATION-
dc.contributor.googleauthorJu, J-h-
dc.contributor.googleauthorOh, S.-
dc.contributor.googleauthorLee, K-m-
dc.contributor.googleauthorYang, W.-
dc.contributor.googleauthorNam, K.S.-
dc.contributor.googleauthorMoon, H-G-
dc.contributor.googleauthorNoh, D-Y-
dc.contributor.googleauthorKim, C.G.-
dc.contributor.googleauthorPark, G.-
dc.contributor.googleauthorPark, J.B.-
dc.relation.code2015001311-
dc.sector.campusS-
dc.sector.daehakCOLLEGE OF NATURAL SCIENCES[S]-
dc.sector.departmentDEPARTMENT OF LIFE SCIENCE-
dc.identifier.pidcgkim-
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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