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Titolo:
Convertases other than furin cleave beta-secretase to its mature form
Autore:
Pinnix, I; Council, JE; Roseberry, B; Onstead, L; Mallender, W; Sucic, J; Sambamurti, K;
Indirizzi:
Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA Mayo Clin Jacksonville FL USA 32224 Neurosci, Jacksonville, FL 32224 USA Univ Michigan, Dept Biol, Flint, MI 48502 USA Univ Michigan Flint MI USA 48502 Michigan, Dept Biol, Flint, MI 48502 USA
Titolo Testata:
FASEB JOURNAL
fascicolo: 8, volume: 15, anno: 2001,
pagine: NIL_515 - NIL_532
SICI:
0892-6638(200106)15:8<NIL_515:COTFCB>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; OVARY CELL STRAIN; ALZHEIMERS-DISEASE; GAMMA-SECRETASE; PEPTIDE; INHIBITORS; SITE; METALLOPROTEASE; PRESENILIN-1; MATURATION;
Keywords:
proprotein convertases; memapsin; aspartyl proteases; proprotein convertases; BACE; zymogen activation; amyloid; Alzheimer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Sambamurti, K Mayo Clin, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA Mayo Clin 4500 San Pablo Rd Jacksonville FL USA 32224 24 USA
Citazione:
I. Pinnix et al., "Convertases other than furin cleave beta-secretase to its mature form", FASEB J, 15(8), 2001, pp. NIL_515-NIL_532

Abstract

An aspartyl protease, Beta-Site APP cleaving enzyme (BACE), was identifiedas the beta -secretase responsible for generating the Amyloid beta proteinthat is believed to cause Alzheimer's disease. BACE has a short propeptidedomain that is absent in the mature enzyme because of proteolytic cleavageafter the sequence RLPR. This sequence is a predicted substrate for proprotein convertases such as furin. To determine the role of furin and other proprotein convertases, we expressed proBACE in a furin-deficient mutant Chinese hamster ovary (CHO-K1) line, RPE. 40. ProBACE signal was higher in RPE.40 than in the CHO-K1 parent, which confirmed that furin plays a role in propeptide removal. However, two independent approaches showed that proBACE is cleaved to mature BACE in RPE. 40: proBACE was rapidly turned over in RPE. 40 although total BACE was stable, and decanoyl-RVKR-chloromethylketone,an inhibitor of the proprotein convertase family, substantially increased proBACE levels in both RPE 40 and CHO-K1. Transient transfection shows thatfurin, PACE4, PC5/6, and PC7 mediate BACE cleavage in vivo, at least when overexpressed. RPE. 40 is proficient in BACE activity despite its furin deficiency. Therefore, our finding that proBACE is cleaved in this mutant leaves open the possibility that maturation is an important regulatory step anda therapeutic target.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/20 alle ore 20:52:32