{"created":"2023-05-15T09:58:09.588476+00:00","id":68,"links":{},"metadata":{"_buckets":{"deposit":"e116528e-03fb-433a-b39f-373ee46d594d"},"_deposit":{"created_by":15,"id":"68","owners":[15],"pid":{"revision_id":0,"type":"depid","value":"68"},"status":"published"},"_oai":{"id":"oai:fdc.repo.nii.ac.jp:00000068","sets":["1:14:15"]},"author_link":[],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2017-03-10"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与大学","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"福岡歯科大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"37114"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（歯学）"}]},"item_10006_description_10":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_description":"2016年度"}]},"item_10006_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Folliculin-interacting protein 1 and 2 (FNIP1 and FNIP2) play critical roles in preventing renal malignancy through their association with the tumor suppressor FLCN. Mutations in FLCN are associated with Birt-Hogg-Dubé (BHD) syndrome, a rare disorder with increased risk of renal cancer. Recent studies indicated that FNIP1/FNIP2 double knockout mice display enlarged polycystic kidneys and renal carcinoma, which phenocopies FLCN knockout mice, suggesting that these two proteins function together to suppress renal cancer. However, the molecular mechanism functionally linking FNIP1/FNIP2 and FLCN remains largely elusive. Here, we demonstrated that FNIP2 protein is unstable and subjected to proteasome-dependent degradation via β-TRCP and Casein Kinase 1 (CK1)-directed ubiquitination in a nutrition-dependent manner. Degradation of FNIP2 leads to lysosomal dissociation of FLCN and subsequent lysosomal association of mTOR, which in turn promotes the proliferation of renal cancer cells. These results indicate that SCFβ-TRCP negatively regulates the FLCN complex by promoting FNIP degradation and provide molecular insight into the pathogenesis of BHD-associated renal cancer.","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第281号"}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Nagashima, Katsuyuki"}]},{"creatorNames":[{"creatorName":"Fukushima, Hidefumi"}]},{"creatorNames":[{"creatorName":"Shimizu, Kouhei"}]},{"creatorNames":[{"creatorName":"Yamada, Aya"}]},{"creatorNames":[{"creatorName":"Hidaka, Masumi"}]},{"creatorNames":[{"creatorName":"Hasumi, Hisashi"}]},{"creatorNames":[{"creatorName":"Ikebe, Tetsuro"}]},{"creatorNames":[{"creatorName":"Fukumoto, Satoshi"}]},{"creatorNames":[{"creatorName":"Okabe, Koji"}]},{"creatorNames":[{"creatorName":"Inuzuka, Hiroyuki"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-03-15"}],"displaytype":"detail","filename":"甲第281号_論文(永嶌).pdf","filesize":[{"value":"8.8 MB"}],"format":"application/pdf","licensetype":"甲第281号_論文(永嶌).pdf","mimetype":"application/pdf","url":{"label":"甲第281号_論文(永嶌)","objectType":"fulltext","url":"https://fdc.repo.nii.ac.jp/record/68/files/甲第281号_論文(永嶌).pdf"},"version_id":"deca4bd8-5388-48d9-ba1f-51871c356271"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-03-15"}],"displaytype":"detail","filename":"甲第281号_論文内容の要旨(永嶌).pdf","filesize":[{"value":"238.6 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"要旨","url":"https://fdc.repo.nii.ac.jp/record/68/files/甲第281号_論文内容の要旨(永嶌).pdf"},"version_id":"1f8f6d4e-5fb0-4a3e-9d98-86ab1a352464"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-03-15"}],"displaytype":"detail","filename":"甲第281号_論文審査結果の要旨(永嶌).pdf","filesize":[{"value":"188.1 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"審査結果の要旨","url":"https://fdc.repo.nii.ac.jp/record/68/files/甲第281号_論文審査結果の要旨(永嶌).pdf"},"version_id":"3967e2d3-5a74-46f9-845d-efe11f2f3a35"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"FNIP"},{"subitem_subject":"FLCN"},{"subitem_subject":"tumor suppressor"},{"subitem_subject":"β-TRCP"},{"subitem_subject":"renal cancer"},{"subitem_subject":"FNIP","subitem_subject_language":"en"},{"subitem_subject":"FLCN","subitem_subject_language":"en"},{"subitem_subject":"tumor suppressor","subitem_subject_language":"en"},{"subitem_subject":"β-TRCP","subitem_subject_language":"en"},{"subitem_subject":"renal cancer","subitem_subject_language":"en"}]},"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":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN complex localization and promotes renal cancer progression.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN complex localization and promotes renal cancer progression.","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"15","path":["15"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2017-03-15"},"publish_date":"2017-03-15","publish_status":"0","recid":"68","relation_version_is_last":true,"title":["Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN complex localization and promotes renal cancer progression."],"weko_creator_id":"15","weko_shared_id":-1},"updated":"2023-06-16T00:39:50.530671+00:00"}