C-terminal region of GADD34 regulates eIF2α dephosphorylation and cell proliferation in CHO-K1 cells 1

• Material Type: 博士論文
• ISSN: 1355-8145
• Title: C-terminal region of GADD34 regulates eIF2α dephosphorylation and cell proliferation in CHO-K1 cells
• Volume: 21 1
• Author/Editor: Otsuka, Ryo; Harada, Nagakatsu; Aoki, Shouhei; Shirai, Kanna; Nishitsuji, Kazuchika; Nozaki, Ayane; Hatakeyama, Adzumi; Shono, Masayuki; Mizusawa, Noriko; Yoshimoto, Katsuhiko; Nakaya, Yutaka; Kitahata, Hiroshi; Sakaue, Hiroshi
• Author Heading: Otsuka, Ryo; Harada, Nagakatsu; Aoki, Shouhei; Shirai, Kanna; Nishitsuji, Kazuchika; Nozaki, Ayane; Hatakeyama, Adzumi; Shono, Masayuki; Mizusawa, Noriko; Yoshimoto, Katsuhiko; Nakaya, Yutaka; Kitahata, Hiroshi; Sakaue, Hiroshi
• Publication, Distribution, etc.: Springer Netherlands
• Publication Date: 2015-08-30
• Publication Date (W3CDTF): 2015-08-30
• Alternative Title: GADD34のC末端領域はCHO-K1細胞におけるeIF2αの脱リン酸化および細胞増殖を調節する; eIF2α dephosphorylation and cell proliferation in CHO-K1 cells
• Periodical title: Cell Stress and Chaperones
• Degree grantor/type: 徳島大学
• Date Granted: 2017-03-23
• Date Granted (W3CDTF): 2017-03-23
• Dissertation Number: 甲第3086号
• Degree Type: 博士（歯学）
• Conferring No. (Dissertation): 甲第3086号
• Text Language Code: eng
• Subject Heading: CHO-K1 cell; GADD34; eIF2α; GSK3β; dephosphorylation; proliferation
• Target Audience: 一般
• Note (General): GADD34 is a member of a growth arrest and DNA damage (GADD)-inducible gene family. Here, we established a novel Chinese hamster ovary (CHO-K1)-K1-derived cell line, CHO-K1-G34M, which carries a nonsense mutation (termed the Q525X mutation) in the GADD34 gene. The Q525X mutant protein lacks the C-terminal 66 amino acids required for GADD34 to bind to and activate protein phosphatase 1 (PP1). We investigated the effects of GADD34 with or without the Q525X mutation on the phosphorylation status of PP1 target proteins, including the α subunit of eukaryotic initiation factor 2 (eIF2α) and glycogen synthase kinase 3β (GSK3β). CHOK1-G34M cells had higher levels of eIF2α phosphorylation compared to the control CHO-K1-normal cells both in the presence and absence of endoplasmic reticulum stress. Overexpression of wild type GADD34 protein in CHOK1-normal cells largely reduced eIF2α phosphorylation, while overexpression of the Q525X mutant did not produce similar reductions. Meanwhile, neither wild type nor Q525X mutation of GADD34 affected the GSK3β phosphorylation status. GADD34 also did not affect the canonical Wnt signaling pathway downstream of GSK3β. Cell proliferation rates were higher, while expression levels of the cyclin dependent kinase inhibitor p21 were lower in CHO-K1-G34M cells compared to the CHO-K1-normal cells. The GADD34 Q525X mutant had a reduced ability to inhibit cell proliferation and enhance p21 expression of the CHO-K1-normal cells compared to the wild type GADD34 protein. These results suggest that the GADD34 protein C-terminal plays important roles in regulating not only eIF2α dephosphorylation but also cell proliferation in CHO-K1 cells.
• DOI: info:doi/10.1007/s12192-015-0633-9; https://doi.org/info:doi/10.1007/s12192-015-0633-9
• Persistent ID (NDL): info:ndljp/pid/10371162; https://dl.ndl.go.jp/pid/10371162
• Collection: 障害者向け資料
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• 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): 2017-07-03T04:10:06+09:00
• Format (IMT): application/pdf
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/110106
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