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http://purl.uniprot.org/citations/12684521http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12684521http://www.w3.org/2000/01/rdf-schema#comment"Presenilin-1 (PS1) and presenilin 2 (PS2) are proposed to be transmembrane aspartyl proteases that cleave amyloid precursor protein and Notch. PS1- and PS2-mediated activities were individually characterized using blastocyst-derived (BD) cells and membranes from PS1+/--PS2-/- and PS1-/-PS2+/+ mice, respectively. The relative amounts of PS1 and PS2 in the various BD cells were determined from the intensities of the anti-PS1 and anti-PS2 immunoblot signals by comparison with standard curves using radiolabeled PS1 and PS2 standards produced by in vitro transcription and translation. Cellular membranes from wild type, PS1-/-PS2+/+, and PS1+/--PS2-/- but not PS1-/-PS2-/-BD cells generated the Abeta40 and Abeta42 products from the C100FLAG substrate. PS1-associated gamma-secretase displays considerably higher specific activity than PS2-associated gamma-secretase. Moreover, the PS1+/-PS2-/-BD cells and corresponding membranes exhibited much higher gamma-secretase activity as compared with other BD cells and membranes. The PS1-mediated gamma-secretase activity correlated better with the amount of PS1 that is modifiable by a photoactivated active site-directed gamma-secretase inhibitor rather than total PS1; hence, only a small portion (<14%) of the PS1 in wild-type membranes appears to be engaged in an active gamma-secretase complex. This finding suggests that PS1 may serve other biological functions in addition to that associated with its gamma-secretase activity. Furthermore, the PS1 gamma-secretase complex and the PS2 gamma-secretase complex activities can be discriminated on the basis of their susceptibility to inhibition by a potent gamma-secretase inhibitor. The distinct yet overlapping enzymatic properties of the PS1 gamma-secretase complex and the PS2 gamma-secretase complex imply that these two putative aspartyl class proteases may contribute to different biological processes."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m300974200"xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Chen E."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Huang Q."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Li Y.M."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Xu M."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Gardell S.J."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Bernstein A."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Donoviel D.B."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Lai M.T."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Register R.B."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Price E."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Hazuda D."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"DiMuzio-Mower J."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Shi X.P."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/author"Crouthamel M.C."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/pages"22475-22481"xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/title"Presenilin-1 and presenilin-2 exhibit distinct yet overlapping gamma-secretase activities."xsd:string
http://purl.uniprot.org/citations/12684521http://purl.uniprot.org/core/volume"278"xsd:string
http://purl.uniprot.org/citations/12684521http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/12684521
http://purl.uniprot.org/citations/12684521http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/12684521
http://purl.uniprot.org/uniprot/Q61144#attribution-938BDA4D5C914DFAA6424369E9490655http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/12684521