Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN complex localization and promotes renal cancer progression.

• Material Type: 博士論文
• Title: Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN complex localization and promotes renal cancer progression.
• Author/Editor: Nagashima, Katsuyuki; Fukushima, Hidefumi; Shimizu, Kouhei; Yamada, Aya; Hidaka, Masumi; Hasumi, Hisashi; Ikebe, Tetsuro; Fukumoto, Satoshi; Okabe, Koji; Inuzuka, Hiroyuki
• Author Heading: Nagashima, Katsuyuki; Fukushima, Hidefumi; Shimizu, Kouhei; Yamada, Aya; Hidaka, Masumi; Hasumi, Hisashi; Ikebe, Tetsuro; Fukumoto, Satoshi; Okabe, Koji; Inuzuka, Hiroyuki
• Publication Date: 2017-03-10
• Publication Date (W3CDTF): 2017-03-10
• Alternative Title: Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN complex localization and promotes renal cancer progression.
• Degree grantor/type: 福岡歯科大学
• Date Granted: 2017-03-10
• Date Granted (W3CDTF): 2017-03-10
• Dissertation Number: 甲第281号
• Degree Type: 博士（歯学）
• Conferring No. (Dissertation): 甲第281号
• Text Language Code: eng
• Subject Heading: FNIP; FLCN; tumor suppressor; β-TRCP; renal cancer
• Target Audience: 一般
• Note (General): 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.
• Persistent ID (NDL): info:ndljp/pid/10318544; https://dl.ndl.go.jp/pid/10318544
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2017-04-02T16:10:31+09:00
• Date Created (W3CDTF): 2017-03-15
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): https://fdc.repo.nii.ac.jp/records/68
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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