{"created":"2023-06-19T10:41:32.864510+00:00","id":1278,"links":{},"metadata":{"_buckets":{"deposit":"26dc4eaa-c314-489f-a876-ef56352ef75a"},"_deposit":{"created_by":3,"id":"1278","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"1278"},"status":"published"},"_oai":{"id":"oai:shiga-med.repo.nii.ac.jp:00001278","sets":["19:219:220"]},"author_link":["2575","2545","2565"],"item_4_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2010-11","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageEnd":"781","bibliographicPageStart":"771","bibliographicVolumeNumber":"115","bibliographic_titles":[{"bibliographic_title":"Journal of Neurochemistry"}]}]},"item_4_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"西村, 正樹"}],"nameIdentifiers":[{},{}]}]},"item_4_description_14":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"pdf","subitem_description_type":"Other"}]},"item_4_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"γ-Secretase mediates intramembranous γ-cleavage and ε-cleavage of β-amyloid precursor protein (APP) to liberate β-amyloid peptide (Aβ) and APP intracellular domain respectively from the membrane. Although the regulatory mechanism of γ-secretase cleavage remains unresolved, a member of the p24 cargo protein family, named p24δ(1) or TMP21, has been identified as an activity-modulating component. The p24 family proteins are divided into four subfamilies (p24α, β, δ and γ). In contrast to p24δ(1), p24β(1) has reportedly no effect on γ-cleavage. In this study, we determined whether p24α(2), p24γ(3) or p24γ(4) modulates APP processing. Knockdown of cellular p24α(2) induced a significant increase in Aβ generation but not in APP intracellular domain production in cell-based and cell-free assays, whereas p24α(2) over-expression suppressed Aβ secretion. By contrast, Aβ secretion was not altered by p24γ(3) or p24γ(4) knockdown. Endogenous p24α(2) co-immunoprecipitated with core components of the γ-secretase complex, and the anti-p24α(2) immunoprecipitate exhibited γ-secretase activity. Mutational disruption of the conserved dilysine ER-retrieval motifs of p24α(2) and p24δ(1) perturbed inhibition of γ-cleavage. Simultaneous knockdown, or co-over-expression, of these proteins had no additive or synergistic effect on Aβ generation. Our findings suggest that dilysine ER-retrieval signal-containing p24 proteins, p24α(2) and p24δ(1), bind with γ-secretase complexes and collaborate in attenuating γ-cleavage of APP. ","subitem_description_type":"Abstract"}]},"item_4_description_42":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"Journal Article","subitem_description_type":"Other"}]},"item_4_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Wiley-Blackwell"}]},"item_4_relation_10":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"20807314","subitem_relation_type_select":"PMID"}}]},"item_4_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"10.1111/j.1471-4159.2010.06977.x"}],"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1111/j.1471-4159.2010.06977.x","subitem_relation_type_select":"DOI"}}]},"item_4_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2010 The Authors. Journal of Neurochemistry "},{"subitem_rights":"© 2010 International Society for Neurochemistry. "}]},"item_4_version_type_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"NISHIMURA, Masaki"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"LIU, Lei"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"HASEGAWA, Hiroshi"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-02-16"}],"displaytype":"detail","filename":"j.1471-4159.2010.06977.x.pdf","filesize":[{"value":"1.9 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"j.1471-4159.2010.06977.x.pdf","url":"https://shiga-med.repo.nii.ac.jp/record/1278/files/j.1471-4159.2010.06977.x.pdf"},"version_id":"85d17d01-fded-4cdf-a61a-6788222a5a3c"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Dilysine retrieval signal-containing p24 proteins collaborate in inhibiting γ-cleavage of   amyloid precursor protein.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Dilysine retrieval signal-containing p24 proteins collaborate in inhibiting γ-cleavage of   amyloid precursor protein."}]},"item_type_id":"4","owner":"3","path":["220"],"pubdate":{"attribute_name":"公開日","attribute_value":"2013-03-19"},"publish_date":"2013-03-19","publish_status":"0","recid":"1278","relation_version_is_last":true,"title":["Dilysine retrieval signal-containing p24 proteins collaborate in inhibiting γ-cleavage of   amyloid precursor protein."],"weko_creator_id":"3","weko_shared_id":3},"updated":"2023-06-19T11:16:46.419135+00:00"}