The HNF-1β-USP28-Claspin pathway upregulates DNA damage-induced Chk1 activation in ovarian clear cell carcinoma.

• Material Type: 博士論文
• ISSN: 1949-2553
• Title: The HNF-1β-USP28-Claspin pathway upregulates DNA damage-induced Chk1 activation in ovarian clear cell carcinoma.
• Volume: 9 25
• Author/Editor: Ito, Fuminori; Yoshimoto, Chiharu; Yamada, Yuki; Sudo, Tamotsu; Kobayashi, Hiroshi
• Author Heading: Ito, Fuminori; Yoshimoto, Chiharu; Yamada, Yuki; Sudo, Tamotsu; Kobayashi, Hiroshi
• Publication, Distribution, etc.: Impact Journals
• Publication Date: 2018-04-03; 9 25
• Publication Date (W3CDTF): 2018-04-03
• Alternative Title: 卵巣明細胞癌においてHNF-1β -USP28-Claspin pathwayはDNA損傷によるChk1活性化を促進する
• Periodical title: Oncotarget
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2019-09-27
• Date Granted (W3CDTF): 2019-09-27
• Dissertation Number: 乙第1435号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 乙第1435号
• Text Language Code: eng
• Subject Heading: hepatocyte nuclear factor-1β; USP28; claspin; Chk1; DNA damage response
• Target Audience: 一般
• Note (General): type:Thesis; Transcription factor hepatocyte nuclear factor 1-beta (HNF-1β) enhances checkpoint kinase 1 (Chk1) activation and promotes G2/M cell cycle progression in ovarian clear cell carcinoma (CCC) following exposure to diverse genotoxic agents including bleomycin. However, the underlying mechanism leading to checkpoint activation of HNF-1β still remains largely unknown. To clarify the effects of HNF-1β on cell cycle checkpoints, human CCC cell lines were transfected with siRNAs targeting HNF-1β, Claspin, USP28, or a control vector. Ubiquitination and stabilization of Claspin protein by HNF-1β was assessed by immunoprecipitation. Loss-of-function studies using RNAi-mediated gene silencing indicated that HNF-1β facilitated the Claspin expression after treatment with a genotoxic agent bleomycin, resulting in accumulation of phosphorylated Chk1 (p-Chk1) and promotion of survival in CCC cell lines. This study showed for the first time that USP28, a de-ubiquitinase crucial for Claspin expression, is one target gene of HNF-1β. Knockdown of endogenous USP28 suppressed the Claspin expression and p-Chk1 activation and cell viability. Our findings identify a novel pathway of the HNF-1β-USP28-Claspin-Chk1 axis in checkpoint signal amplification in response to DNA damage. Targeting this pathway may represent a putative, novel, anticancer strategy in ovarian CCC.; 博士（医学）・乙第1435号・令和元年9月27日; Copyright © 2018 Impact Journals, LLC; Copyright © Ito et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CCBY 3.0 https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source arecredited.; identifier:Oncotarget Vol.9 No.25 p.17512-17522 (2018 Apr); identifier:19492553; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3671; identifier:Oncotarget, 9(25): 17512-17522
• DOI: info:doi/10.18632/oncotarget.24776; https://doi.org/info:doi/10.18632/oncotarget.24776
• Persistent ID (NDL): info:ndljp/pid/11490385; https://dl.ndl.go.jp/pid/11490385
• 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): 2020-05-25T09:38:44+09:00
• 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): http://hdl.handle.net/10564/3671
• 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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