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Titolo:
Post-translational processing of beta-secretase (beta-amyloid-converting enzyme) and its ectodomain shedding - The pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid-beta production
Autore:
Benjannet, S; Elagoz, A; Wickham, L; Mamarbachi, M; Munzer, JS; Basak, A; Lazure, C; Cromlish, JA; Sisodia, S; Checler, F; Chretien, M; Seidah, NG;
Indirizzi:
Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada Clin Res Inst Montreal Montreal PQ Canada H2W 1R7 eal, PQ H2W 1R7, Canada Ottawa Hosp, Loeb Hlth Res Inst, Dis Aging Unit, Ottawa, ON K1Y 4K9, Canada Ottawa Hosp Ottawa ON Canada K1Y 4K9 ing Unit, Ottawa, ON K1Y 4K9, Canada Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada Clin Res Inst Montreal Montreal PQ Canada H2W 1R7 eal, PQ H2W 1R7, Canada Univ Chicago, Dept Pharmacol & Physiol Sci, Chicago, IL 60637 USA Univ Chicago Chicago IL USA 60637 ol & Physiol Sci, Chicago, IL 60637 USA CNRS, Inst Pharmacol Mol & Cellulaire, UPR 411, F-06560 Valbonne, France CNRS Valbonne France F-06560 llulaire, UPR 411, F-06560 Valbonne, France
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 14, volume: 276, anno: 2001,
pagine: 10879 - 10887
SICI:
0021-9258(20010406)276:14<10879:PPOB(E>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; PROPROTEIN CONVERTASE; IN-VITRO; ASPARTYL PROTEASE; HUMAN BRAIN; CLEAVAGE; FURIN; BACE; IDENTIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Seidah, NG Clin Res Inst Montreal, 110 Pine Ave W, Montreal, PQ H2W 1R7, Canada Clin Res Inst Montreal 110 Pine Ave W Montreal PQ Canada H2W 1R7
Citazione:
S. Benjannet et al., "Post-translational processing of beta-secretase (beta-amyloid-converting enzyme) and its ectodomain shedding - The pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid-beta production", J BIOL CHEM, 276(14), 2001, pp. 10879-10887

Abstract

Processing of the beta -amyloid precursor protein (beta APP) by beta- and gamma -secretases generates the amyloidogenic peptide A beta, a major factor in the etiology of Alzheimer's disease. Following the recent identification of the beta -secretase beta -amyloid-converting enzyme (BACE), we hereininvestigate its zymogen processing, molecular properties, and cellular trafficking. Our data show that among the proprotein convertase family members, furin is the major converting enzyme of pro-BACE into BACE within the trans-Golgi network of HK293 cells. While we demonstrate that; the 24-amino acid prosegment is required for the efficient exit of pro-BACE from the endoplasmic reticulum, it may not play a strong inhibitory role since we observethat pro-BACE can produce significant quantities of the Swedish mutant beta APP(sw) beta -secretase product C99, BACE is palmitoylated at three Cys residues within its transmembrane/cytosolic tail and is sulfated at mature N-glycosylated moieties, Data with three different antibodies show that a small fraction of membrane-bound BACE is shed into the medium and that the extent of ectodomain shedding is palmitoylation-dependent. Overexpression of full-length BACE causes a significant increase in the production of C99 anda decrease in the alpha -secretase product APPs alpha. Although there is little increase in the generation of A beta by full-length BACE, overexpression of either a soluble form of BACE (equivalent to the shed form) or one lacking the prosegment leads to enhanced A beta levels. These findings suggest that the shedding of BACE may play a role in the amyloidogenic processing of beta APP.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 08:03:57