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Article: Dexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcription

TitleDexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcription
Authors
Issue Date2008
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2008, v. 283 n. 50, p. 34728-34737 How to Cite?
AbstractFE65 is an adaptor protein that binds to and forms a transcriptionally active complex with the γ-secretase-derived amyloid precursor protein (APP) intracellular domain. The regulatory mechanisms of FE65-APP-mediated transcription are still not clear. In this report, we demonstrate that Dexras1, a Ras family small G protein, binds to FE65 PTB2 domain and potently suppresses the FE65-APP-mediated transcription. The suppression is not via competition for binding of FE65 between Dexras1 and APP because the two proteins can simultaneously bind to the FE65 PTB2 domain. Phosphorylation of FE65 tyrosine 547 within the PTB2 domain has been shown to enhance FE65-APP-mediated transcription but not to influence binding to APP. Here we find that this phosphorylation event reduces the binding between Dexras1 and FE65. We also demonstrate that Dexras1 inhibits the FE65-APP-mediated transcription of glycogen synthase kinase 3β (GSK3β). Moreover, small interfering RNA knockdown of Dexras1 enhances GSK3β expression and increases phosphorylation of Tau, a GSK3β substrate. Thus, Dexras1 functions as a suppressor of FE65-APP-mediated transcription, and FE65 tyrosine 547 phosphorylation enhances FE65-APP-mediated transcription, at least in part, by modulating the interaction between FE65 and Dexras1. These findings reveal a novel regulatory mechanism for FE65-APP-mediated signaling. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/149708
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
Funding AgencyGrant Number
Council Hong Kong, a Chinese University of Hong Kong
United Kingdom Medical Research Council, Biotechnology and Biological Sciences Research Council
European Union NeuroNE,
Alzheimer Society
Funding Information:

This work was supported by the Research Grant Council Hong Kong, a Chinese University of Hong Kong direct grant scheme, the Wellcome Trust, United Kingdom Medical Research Council, Biotechnology and Biological Sciences Research Council, European Union NeuroNE, the Alzheimer Society, the Alzheimer Research Trust, and the Alzheimer Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact.

References

 

DC FieldValueLanguage
dc.contributor.authorLau, KFen_US
dc.contributor.authorChan, WMen_US
dc.contributor.authorPerkinton, MSen_US
dc.contributor.authorTudor, ELen_US
dc.contributor.authorChang, RCCen_US
dc.contributor.authorChan, HYEen_US
dc.contributor.authorMcloughlin, DMen_US
dc.contributor.authorMiller, CCJen_US
dc.date.accessioned2012-06-26T05:57:25Z-
dc.date.available2012-06-26T05:57:25Z-
dc.date.issued2008en_US
dc.identifier.citationJournal Of Biological Chemistry, 2008, v. 283 n. 50, p. 34728-34737en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/149708-
dc.description.abstractFE65 is an adaptor protein that binds to and forms a transcriptionally active complex with the γ-secretase-derived amyloid precursor protein (APP) intracellular domain. The regulatory mechanisms of FE65-APP-mediated transcription are still not clear. In this report, we demonstrate that Dexras1, a Ras family small G protein, binds to FE65 PTB2 domain and potently suppresses the FE65-APP-mediated transcription. The suppression is not via competition for binding of FE65 between Dexras1 and APP because the two proteins can simultaneously bind to the FE65 PTB2 domain. Phosphorylation of FE65 tyrosine 547 within the PTB2 domain has been shown to enhance FE65-APP-mediated transcription but not to influence binding to APP. Here we find that this phosphorylation event reduces the binding between Dexras1 and FE65. We also demonstrate that Dexras1 inhibits the FE65-APP-mediated transcription of glycogen synthase kinase 3β (GSK3β). Moreover, small interfering RNA knockdown of Dexras1 enhances GSK3β expression and increases phosphorylation of Tau, a GSK3β substrate. Thus, Dexras1 functions as a suppressor of FE65-APP-mediated transcription, and FE65 tyrosine 547 phosphorylation enhances FE65-APP-mediated transcription, at least in part, by modulating the interaction between FE65 and Dexras1. These findings reveal a novel regulatory mechanism for FE65-APP-mediated signaling. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.subject.meshAmyloid Beta-Protein Precursor - Chemistry - Metabolismen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBinding, Competitiveen_US
dc.subject.meshCho Cellsen_US
dc.subject.meshCricetinaeen_US
dc.subject.meshCricetulusen_US
dc.subject.meshGlycogen Synthase Kinase 3 - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshNerve Tissue Proteins - Metabolismen_US
dc.subject.meshNuclear Proteins - Metabolismen_US
dc.subject.meshRatsen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshTranscription, Geneticen_US
dc.subject.meshRas Proteins - Metabolismen_US
dc.titleDexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcriptionen_US
dc.typeArticleen_US
dc.identifier.emailChang, RCC:rccchang@hkucc.hku.hken_US
dc.identifier.authorityChang, RCC=rp00470en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.M801874200en_US
dc.identifier.pmid18922798-
dc.identifier.scopuseid_2-s2.0-58049200124en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58049200124&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume283en_US
dc.identifier.issue50en_US
dc.identifier.spage34728en_US
dc.identifier.epage34737en_US
dc.identifier.isiWOS:000261469100029-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLau, KF=7401560031en_US
dc.identifier.scopusauthoridChan, WM=7403918030en_US
dc.identifier.scopusauthoridPerkinton, MS=6602222742en_US
dc.identifier.scopusauthoridTudor, EL=8919447600en_US
dc.identifier.scopusauthoridChang, RCC=7403713410en_US
dc.identifier.scopusauthoridChan, HYE=7403402719en_US
dc.identifier.scopusauthoridMcLoughlin, DM=7005061686en_US
dc.identifier.scopusauthoridMiller, CCJ=8980202200en_US

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