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Article: Transcriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1

TitleTranscriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1
Authors
Issue Date2010
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35503
Citation
Journal Of Cellular Biochemistry, 2010, v. 109 n. 4, p. 782-793 How to Cite?
AbstractFE65 is a neuronal-enriched adaptor protein that binds to the Alzheimer's disease amyloid precursor protein (APP). FE65 forms a transcriptionally active complex with the APP intracellular domain (AICD). The precise gene targets for this complex are unclear but several Alzheimer's disease-linked genes have been proposed. Additionally, evidence suggests that FE65 influences APP metabolism. The mechanism by which FE65 expression is regulated is as yet unknown. To gain insight into the regulatory mechanism, we cloned a 1.6 kb fragment upstream of the human FE65 gene and found that it possesses particularly strong promoter activity in neurones. To delineate essential regions in the human FE65 promoter, a series of deletion mutants were generated. The minimal FE65 promoter was located between -100 and +5, which contains a functional Sp1 site. Overexpression of the transcription factor Sp1 potentiates the FE65 promoter activity. Conversely, suppression of the FE65 promoter was observed in cells either treated with an Sp1 inhibitor or in which Sp1 was knocked down. Furthermore, reduced levels of Sp1 resulted in downregulation of endogenous FE65 mRNA and protein. These findings reveal that Sp1 plays a crucial role in transcriptional control of the human FE65 gene. © 2010 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/149735
ISSN
2015 Impact Factor: 3.446
2015 SCImago Journal Rankings: 1.520
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council Hong Kong469207
CUHK2030364
2030386
Wellcome Trust
UK Medical Research Council
Biotechnology and Biological Sciences Research Council
Alzheimer's Research Trust
Alzheimer's Association
Funding Information:

This work was supported by funds from the Research Grant Council Hong Kong (469207) and the CUHK direct grant scheme (2030364 and 2030386), the Wellcome Trust, UK Medical Research Council, Biotechnology and Biological Sciences Research Council, Alzheimer's Research Trust and Alzheimer's Association. We thank Dicky Siu for technical assistance. We are grateful to Guntram Snake for the pN3 and pN3-Sp1 plasmic's.

References

 

DC FieldValueLanguage
dc.contributor.authorYu, HTen_US
dc.contributor.authorChan, WWLen_US
dc.contributor.authorChai, KHen_US
dc.contributor.authorLee, CWCen_US
dc.contributor.authorChang, RCCen_US
dc.contributor.authorYu, MSen_US
dc.contributor.authorMcloughlin, DMen_US
dc.contributor.authorMiller, CCJen_US
dc.contributor.authorLau, KFen_US
dc.date.accessioned2012-06-26T05:57:48Z-
dc.date.available2012-06-26T05:57:48Z-
dc.date.issued2010en_US
dc.identifier.citationJournal Of Cellular Biochemistry, 2010, v. 109 n. 4, p. 782-793en_US
dc.identifier.issn0730-2312en_US
dc.identifier.urihttp://hdl.handle.net/10722/149735-
dc.description.abstractFE65 is a neuronal-enriched adaptor protein that binds to the Alzheimer's disease amyloid precursor protein (APP). FE65 forms a transcriptionally active complex with the APP intracellular domain (AICD). The precise gene targets for this complex are unclear but several Alzheimer's disease-linked genes have been proposed. Additionally, evidence suggests that FE65 influences APP metabolism. The mechanism by which FE65 expression is regulated is as yet unknown. To gain insight into the regulatory mechanism, we cloned a 1.6 kb fragment upstream of the human FE65 gene and found that it possesses particularly strong promoter activity in neurones. To delineate essential regions in the human FE65 promoter, a series of deletion mutants were generated. The minimal FE65 promoter was located between -100 and +5, which contains a functional Sp1 site. Overexpression of the transcription factor Sp1 potentiates the FE65 promoter activity. Conversely, suppression of the FE65 promoter was observed in cells either treated with an Sp1 inhibitor or in which Sp1 was knocked down. Furthermore, reduced levels of Sp1 resulted in downregulation of endogenous FE65 mRNA and protein. These findings reveal that Sp1 plays a crucial role in transcriptional control of the human FE65 gene. © 2010 Wiley-Liss, Inc.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35503en_US
dc.relation.ispartofJournal of Cellular Biochemistryen_US
dc.subject.meshAmyloid Beta-Protein Precursoren_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshHumansen_US
dc.subject.meshNerve Tissue Proteins - Analysis - Geneticsen_US
dc.subject.meshNeuronsen_US
dc.subject.meshNuclear Proteins - Analysis - Geneticsen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshRna, Messenger - Analysisen_US
dc.subject.meshSp1 Transcription Factor - Physiologyen_US
dc.subject.meshTranscription, Geneticen_US
dc.titleTranscriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1en_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.doi10.1002/jcb.22457en_US
dc.identifier.pmid20091743-
dc.identifier.scopuseid_2-s2.0-77749311404en_US
dc.identifier.hkuros170358-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77749311404&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume109en_US
dc.identifier.issue4en_US
dc.identifier.spage782en_US
dc.identifier.epage793en_US
dc.identifier.isiWOS:000275559000017-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYu, HT=36672403800en_US
dc.identifier.scopusauthoridChan, WWL=36670944700en_US
dc.identifier.scopusauthoridChai, KH=36670941600en_US
dc.identifier.scopusauthoridLee, CWC=36671542000en_US
dc.identifier.scopusauthoridChang, RCC=7403713410en_US
dc.identifier.scopusauthoridYu, MS=35346047600en_US
dc.identifier.scopusauthoridMcLoughlin, DM=7005061686en_US
dc.identifier.scopusauthoridMiller, CCJ=8980202200en_US
dc.identifier.scopusauthoridLau, KF=7401560031en_US

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