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Title: Regulated intramembrane proteolysis of amyloid precursor protein and regulation of expression of putative target genes
Authors: Hébert, Sébastien
Serneels, Lutgarde
Tolia, Alexandra
Craessaerts, Kathleen
Derks, Carmen
Filippov, Mikhail A
Müller, Ulrike
De Strooper, Bart # ×
Issue Date: Jul-2006
Publisher: Published for EMBO by Oxford University Press
Series Title: EMBO Reports vol:7 issue:7 pages:739-45
Abstract: gamma-Secretase-dependent regulated intramembrane proteolysis of amyloid precursor protein (APP) releases the APP intracellular domain (AICD). The question of whether this domain, like the Notch intracellular domain, is involved in nuclear signalling is highly controversial. Although some reports suggest that AICD regulates the expression of KAI1, glycogen synthase kinase-3beta, Neprilysin and APP, we found no consistent effects of gamma-secretase inhibitors or of genetic deficiencies in the gamma-secretase complex or the APP family on the expression levels of these genes in cells and tissues. Finally, we demonstrate that Fe65, an important AICD-binding protein, transactivates a wide variety of different promoters, including the viral simian virus 40 promoter, independent of AICD coexpression. Overall, the four currently proposed target genes are at best indirectly and weakly influenced by APP processing. Therefore, inhibition of APP processing to decrease Abeta generation in Alzheimer's disease will not interfere significantly with the function of these genes.
ISSN: 1469-221X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Laboratory for the Research of Neurodegenerative Diseases
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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