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

Hoi Tin Yu, William Wai Lun Chan, Ka Ho Chai, Chris Wing Cheung Lee, Raymond Chuen Chung Chang, Man Shan Yu, Declan M. McLoughlin, Christopher C.J. Miller, Kwok Fai Lau

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)782-793
Number of pages12
JournalJournal of cellular biochemistry
Volume109
Issue number4
DOIs
StatePublished - Mar 1 2010

Keywords

  • Amyloid precursor protein
  • FE65
  • Promoter
  • Sp1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yu, H. T., Chan, W. W. L., Chai, K. H., Lee, C. W. C., Chang, R. C. C., Yu, M. S., McLoughlin, D. M., Miller, C. C. J., & Lau, K. F. (2010). Transcriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1. Journal of cellular biochemistry, 109(4), 782-793. https://doi.org/10.1002/jcb.22457