| http://purl.uniprot.org/citations/30626721 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30626721 | http://www.w3.org/2000/01/rdf-schema#comment | "Intramembrane proteolysis of transmembrane substrates by the presenilin-γ-secretase complex is preceded and regulated by shedding of the substrate's ectodomain by α- or β-secretase. We asked whether β- and γ-secretases interact to mediate efficient sequential processing of APP, generating the amyloid β (Aβ) peptides that initiate Alzheimer's disease. We describe a hitherto unrecognized multiprotease complex containing active β- and γ-secretases. BACE1 coimmunoprecipitated and cofractionated with γ-secretase in cultured cells and in mouse and human brain. An endogenous high molecular weight (HMW) complex (∼5 MD) containing β- and γ-secretases and holo-APP was catalytically active in vitro and generated a full array of Aβ peptides, with physiological Aβ42/40 ratios. The isolated complex responded properly to γ-secretase modulators. Alzheimer's-causing mutations in presenilin altered the Aβ42/40 peptide ratio generated by the HMW β/γ-secretase complex indistinguishably from that observed in whole cells. Thus, Aβ is generated from holo-APP by a BACE1-γ-secretase complex that provides sequential, efficient RIP processing of full-length substrates to final products."xsd:string |
| http://purl.uniprot.org/citations/30626721 | http://purl.org/dc/terms/identifier | "doi:10.1083/jcb.201806205"xsd:string |
| http://purl.uniprot.org/citations/30626721 | http://purl.uniprot.org/core/author | "Ding L."xsd:string |
| http://purl.uniprot.org/citations/30626721 | http://purl.uniprot.org/core/author | "Liu L."xsd:string |
| http://purl.uniprot.org/citations/30626721 | http://purl.uniprot.org/core/author | "Selkoe D.J."xsd:string |
| http://purl.uniprot.org/citations/30626721 | http://purl.uniprot.org/core/author | "Wolfe M.S."xsd:string |
| http://purl.uniprot.org/citations/30626721 | http://purl.uniprot.org/core/author | "Rovere M."xsd:string |
| http://purl.uniprot.org/citations/30626721 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30626721 | http://purl.uniprot.org/core/name | "J Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/30626721 | http://purl.uniprot.org/core/pages | "644-663"xsd:string |
| http://purl.uniprot.org/citations/30626721 | http://purl.uniprot.org/core/title | "A cellular complex of BACE1 and gamma-secretase sequentially generates Abeta from its full-length precursor."xsd:string |
| http://purl.uniprot.org/citations/30626721 | http://purl.uniprot.org/core/volume | "218"xsd:string |
| http://purl.uniprot.org/citations/30626721 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30626721 |
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