BIG3 Inhibits the Estrogen-Dependent Nuclear Translocation of PHB2 via Multiple Karyopherin-Alpha Proteins in Breast Cancer Cells

• Material Type: 博士論文
• Title: BIG3 Inhibits the Estrogen-Dependent Nuclear Translocation of PHB2 via Multiple Karyopherin-Alpha Proteins in Breast Cancer Cells
• Author/Editor: Kim, Nam-Hee; Yoshimaru, Tetsuro; Chen, Yi-An; Matsuo, Taisuke; Komatsu, Masato; Miyoshi, Yasuo; Tanaka, Eiji; Sasa, Mitsunori; Mizuguchi, Kenji; Katagiri, Toyomasa
• Author Heading: Kim, Nam-Hee; Yoshimaru, Tetsuro; Chen, Yi-An; Matsuo, Taisuke; Komatsu, Masato; Miyoshi, Yasuo; Tanaka, Eiji; Sasa, Mitsunori; Mizuguchi, Kenji; Katagiri, Toyomasa
• Publication, Distribution, etc.: PLOS
• Publication Date: 2015-06-08
• Publication Date (W3CDTF): 2015-06-08
• Alternative Title: エストロゲン受容体陽性乳がん細胞において、BIG3は複数のKaryopherin-αを介したPHB2のエストロゲン依存性核移行を阻害する
• Periodical title: PLOS ONE
• No. or year of volume/issue: 10 6
• Volume: 10
• Issue: 6
• Pages: e0127707-
• ISSN (Periodical Title): ISSN : 1932-6203
• Degree grantor/type: 徳島大学
• Date Granted: 2015-07-16
• Dissertation Number: 甲第2860号
• Degree Type: 博士（歯学）
• Text Language Code: eng
• Subject Heading: Karyopherin-alpha; estrogen; nuclear translocation; breast cancer; BIG3; PHB2
• Target Audience: 一般
• Note (General): We recently reported that brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) binds Prohibitin 2 (PHB2) in cytoplasm, thereby causing a loss of function of the PHB2 tumor suppressor in the nuclei of breast cancer cells. However, little is known regarding the mechanism by which BIG3 inhibits the nuclear translocation of PHB2 into breast cancer cells. Here, we report that BIG3 blocks the estrogen (E2)-dependent nuclear import of PHB2 via the karyopherin alpha (KPNA) family in breast cancer cells. We found that overexpressed PHB2 interacted with KPNA1, KPNA5, and KPNA6, thereby leading to the E2-dependent translocation of PHB2 into the nuclei of breast cancer cells. More importantly, knockdown of each endogenous KPNA by siRNA caused a significant inhibition of E2-dependent translocation of PHB2 in BIG3-depleted breast cancer cells, thereby enhancing activation of estrogen receptor alpha (ERα). These data indicated that BIG3 may block the KPNAs (KPNA1, KPNA5, and KPNA6) binding region(s) of PHB2, thereby leading to inhibition of KPNAs-mediated PHB2 nuclear translocation in the presence of E2 in breast cancer cells. Understanding this regulation of PHB2 nuclear import may provide therapeutic strategies for controlling E2/ERα signals in breast cancer cells.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): Copyright: © 2015 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• Related Material (DOI): 10.1371/journal.pone.0127707
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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