Processing of β-Amyloid Precursor-like Protein-1 and -2 by γ-Secretase Regulates Transcription
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 th...
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Published in | The Journal of biological chemistry Vol. 277; no. 46; p. 44195 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
15.11.2002
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Online Access | Get full text |
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Summary: | 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 A PP- l ike I ntracellular D omain 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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M208110200 |