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Titolo:
The amyloid precursor protein (APP)-cytoplasmic fragment generated by gamma-secretase is rapidly degraded but distributes partially in a nuclear fraction of neurones in culture
Autore:
Cupers, P; Orlans, I; Craessaerts, K; Annaert, W; De Strooper, B;
Indirizzi:
Flanders Interuniv Inst Biotechnol, Neuronal Cell Biol Grp, CME, B-3000 Louvain, Belgium Flanders Interuniv Inst Biotechnol Louvain Belgium B-3000 uvain, Belgium Catholic Univ Louvain, B-3000 Louvain, Belgium Catholic Univ Louvain Louvain Belgium B-3000 in, B-3000 Louvain, Belgium
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 5, volume: 78, anno: 2001,
pagine: 1168 - 1178
SICI:
0022-3042(200109)78:5<1168:TAPP(F>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHOSPHOTYROSINE-BINDING DOMAIN; ALZHEIMERS-DISEASE; INTRACELLULAR DOMAIN; CYTOPLASMIC DOMAIN; PROTEOLYTIC CLEAVAGE; HIPPOCAMPAL-NEURONS; SIGNAL-TRANSDUCTION; BETA-PEPTIDE; NOTCH; PRESENILIN-1;
Keywords:
amyloid precursor protein; APP-C59; gamma-secretase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Annaert, W Flanders Interuniv Inst Biotechnol, Neuronal Cell Biol Grp, CME, Herestr 49, B-3000 Louvain, Belgium Flanders Interuniv Inst Biotechnol Herestr 49 Louvain Belgium B-3000
Citazione:
P. Cupers et al., "The amyloid precursor protein (APP)-cytoplasmic fragment generated by gamma-secretase is rapidly degraded but distributes partially in a nuclear fraction of neurones in culture", J NEUROCHEM, 78(5), 2001, pp. 1168-1178

Abstract

The gamma -secretase cleavage is the last step in the generation of the beta -amyloid peptide (A beta) from the amyloid precursor protein (APP). The A beta precipitates in the amyloid plaques in the brain of Alzheimer's disease patients. The fate of the intracellular APP carboxy-terminal stub generated together with A beta has been, in contrast, only poorly documented. The analogies between the processing of APP and other transmembrane proteins like SREBP and Notch suggests that this intracellular fragment could have important signalling functions. We demonstrate here that APP-C59 is rapidly degraded (half-life similar to5 min) when overexpressed in baby hamster kidney cells or primary cultures of neurones by a mechanism that is not inhibited by endosomal/lysosomal or proteasome inhibitors. Furthermore, APP-C59 binds to the DNA binding protein Fe65, although this does not increase the half-life of APP-C59. Finally, we demonstrate that a fraction of APP-C59 becomes redistributed to the nuclear detergent-insoluble pellet, in which the transcription factor SP1 is also present. Overall our results reinforce theanalogy between Notch and APP processing, and suggest that the APP intracellular domain, like the Notch intracellular domain, could have a role in signalling events from the plasma membrane to the nucleus.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 12:18:28