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

Hdl Handle:
http://hdl.handle.net/10147/128732
Title:
Transcriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1.
Authors:
Yu, Hoi-Tin; Chan, William Wai-Lun; Chai, Ka-Ho; Lee, Chris Wing-Cheung; Chang, Raymond Chuen-Chung; Yu, Man-Shan; McLoughlin, Declan M; Miller, Christopher C J; Lau, Kwok-Fai
Affiliation:
Department of Biochemistry (Science), The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR.
Citation:
Transcriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1. 2010, 109 (4):782-93 J. Cell. Biochem.
Journal:
Journal of cellular biochemistry
Issue Date:
1-Mar-2010
URI:
http://hdl.handle.net/10147/128732
DOI:
10.1002/jcb.22457
PubMed ID:
20091743
Additional Links:
http://dx.doi.org/10.1002/jcb.22457
Abstract:
FE65 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.
Language:
en
MeSH:
Amyloid beta-Protein Precursor; Gene Expression Regulation; Humans; Nerve Tissue Proteins; Neurons; Nuclear Proteins; Promoter Regions, Genetic; RNA, Messenger; Sp1 Transcription Factor; Transcription, Genetic
ISSN:
1097-4644

Full metadata record

DC FieldValue Language
dc.contributor.authorYu, Hoi-Tinen
dc.contributor.authorChan, William Wai-Lunen
dc.contributor.authorChai, Ka-Hoen
dc.contributor.authorLee, Chris Wing-Cheungen
dc.contributor.authorChang, Raymond Chuen-Chungen
dc.contributor.authorYu, Man-Shanen
dc.contributor.authorMcLoughlin, Declan Men
dc.contributor.authorMiller, Christopher C Jen
dc.contributor.authorLau, Kwok-Faien
dc.date.accessioned2011-04-27T09:12:36Z-
dc.date.available2011-04-27T09:12:36Z-
dc.date.issued2010-03-01-
dc.identifier.citationTranscriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1. 2010, 109 (4):782-93 J. Cell. Biochem.en
dc.identifier.issn1097-4644-
dc.identifier.pmid20091743-
dc.identifier.doi10.1002/jcb.22457-
dc.identifier.urihttp://hdl.handle.net/10147/128732-
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.-
dc.language.isoenen
dc.relation.urlhttp://dx.doi.org/10.1002/jcb.22457en
dc.subject.meshAmyloid beta-Protein Precursor-
dc.subject.meshGene Expression Regulation-
dc.subject.meshHumans-
dc.subject.meshNerve Tissue Proteins-
dc.subject.meshNeurons-
dc.subject.meshNuclear Proteins-
dc.subject.meshPromoter Regions, Genetic-
dc.subject.meshRNA, Messenger-
dc.subject.meshSp1 Transcription Factor-
dc.subject.meshTranscription, Genetic-
dc.titleTranscriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1.en
dc.contributor.departmentDepartment of Biochemistry (Science), The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR.en
dc.identifier.journalJournal of cellular biochemistryen
dc.description.provinceLeinster-

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