| http://purl.uniprot.org/citations/20299451 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20299451 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20299451 | http://www.w3.org/2000/01/rdf-schema#comment | "Drosophila Crumbs has been reported to attenuate Notch signaling by inhibition of gamma-secretase cleavage at the wing margins. gamma-Secretase is an intramembrane protease that is responsible for the generation of amyloid-beta (Abeta) peptides from the beta-amyloid precursor protein (APP). Here, we re-examined gamma-secretase inhibition by human CRB2, which is the most abundant Crumbs ortholog in the brain. Transfected CRB2 inhibited proteolytic production of Abeta and APP intracellular domains from APP C-terminal fragments in HEK293 and SH-SY5Y cells. Conversely, knockdown of endogenous CRB2 increased gamma-secretase cleavage products in SH-SY5Y cells. CRB2 inhibition of gamma-cleavage was also detected in cell-free assays. CRB2 interacted with the gamma-secretase complex, but was not a competitive substrate for gamma-cleavage. The transmembrane domain of CRB2 was indispensable for inhibition of Abeta generation and mediated CRB2 binding with the gamma-secretase complex. In addition, the cytoplasmic domain appeared to play a supportive role in gamma-secretase inhibition, whereas mutational disruption of the two protein-binding motifs involved in the formation of cell adhesion complexes did not affect gamma-secretase inhibition. Co-overexpression of presenilin-1 or APH-1 abrogated gamma-secretase inhibition probably through prevention of the incorporation of CRB2 into the gamma-secretase complex. Our results suggest that CRB2 functions as an inhibitory binding protein that is involved in the formation of a mature but inactive pool of the gamma-secretase complex."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.038760"xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.038760"xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Nishimura M."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Nishimura M."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Suzuki T."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Suzuki T."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Takeda M."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Takeda M."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Matsuo A."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Matsuo A."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Araki W."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Araki W."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Hasegawa H."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Hasegawa H."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Roepman R."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Roepman R."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Okochi M."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Okochi M."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Mitsuishi Y."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Mitsuishi Y."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Tagami S."xsd:string |
| http://purl.uniprot.org/citations/20299451 | http://purl.uniprot.org/core/author | "Tagami S."xsd:string |