Regulated intramembrane proteolysis of amyloid precursor protein and regulation of expression of putative target genes.

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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Hébert SS,Serneels L,Tolia A,Craessaerts K,Derks C,Filippov MA,Müller U,De Strooper B

doi

10.1038/sj.embor.7400704

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

739-45

issue

7

eissn

1469-221X

issn

1469-3178

pii

7400704

journal_volume

7

pub_type

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