Processing of β-amyloid precursor-like protein-1 and -2 by γ-secretase regulates transcription

Meir H. Scheinfeld, Enrico Ghersi, Karen Laky, B. J. Fowlkes, Luciano D'Adamio

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

The familial Alzheimer's disease gene product β-amyloid (Aβ) precursor protein (APP) is processed by the β- and γ-secretases to produce Aβ as well as AID (APP Intracellular Domain) which is derived from the extreme carboxyl terminus of APP. AID was originally shown to lower the cellular threshold to apoptosis and more recently has been shown to modulate gene expression such that it represses Notch-dependent gene expression while in combination with Fe65 it enhances gene activation. Here we report that the two other members of the APP family, β-amyloid precursor-like protein-1 and -2 (APLP1 and APLP2), are also processed by the γ-secretase in a Presenilin 1-dependent manner. Furthermore, the extreme carboxyl-terminal fragments produced by this processing (here termed APP-like Intracellular Domain or ALID1 and ALID2) are able to enhance Fe65-dependent gene activation, similar to what has been reported for AID. Considering that only APP and not the APLPs have been linked to familial Alzheimer's disease (AD), this data should help in understanding the physiologic roles of the APP family members and in differentiating these functions from the pathologic role of APP in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)44195-44201
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number46
DOIs
StatePublished - Nov 15 2002

Fingerprint

Amyloid Precursor Protein Secretases
Protein Precursors
Amyloid beta-Protein Precursor
Transcription
Amyloid
Serum Amyloid A Protein
Processing
Alzheimer Disease
Proteins
Transcriptional Activation
Genes
Gene expression
Presenilin-1
Gene Expression
Chemical activation
Apoptosis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Processing of β-amyloid precursor-like protein-1 and -2 by γ-secretase regulates transcription. / Scheinfeld, Meir H.; Ghersi, Enrico; Laky, Karen; Fowlkes, B. J.; D'Adamio, Luciano.

In: Journal of Biological Chemistry, Vol. 277, No. 46, 15.11.2002, p. 44195-44201.

Research output: Contribution to journalArticle

Scheinfeld, Meir H. ; Ghersi, Enrico ; Laky, Karen ; Fowlkes, B. J. ; D'Adamio, Luciano. / Processing of β-amyloid precursor-like protein-1 and -2 by γ-secretase regulates transcription. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 46. pp. 44195-44201.
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