Aberrant upregulation of the endogenous PP2A inhibitor CIP2A is vital for myeloma cell growth and survival

• 資料種別: 博士論文
• タイトル: Aberrant upregulation of the endogenous PP2A inhibitor CIP2A is vital for myeloma cell growth and survival
• 著者・編者: Shimizu, So; Teramachi, Jumpei; Harada, Takeshi; Hiasa, Masahiro; Tenshin, Hirofumi; Oda, Asuka; Seki, Aiko; Inoue, Yusuke; Tanimoto, Kotaro; Higa, Yoshiki; Oura, Masahiro; Sogabe, Kimiko; Hara, Tomoyo; Sumitani, Ryohei; Maruhashi, Tomoko; Yamagami, Hiroki; Sawa, Yoshihiko; Endo, Itsuro; Tsuneyama, Koichi; Matsumoto, Toshio; Tanaka, Eiji; Abe, Masahiro
• 著者標目: Shimizu, So; Teramachi, Jumpei; Harada, Takeshi; Hiasa, Masahiro; Tenshin, Hirofumi; Oda, Asuka; Seki, Aiko; Inoue, Yusuke; Tanimoto, Kotaro; Higa, Yoshiki; Oura, Masahiro; Sogabe, Kimiko; Hara, Tomoyo; Sumitani, Ryohei; Maruhashi, Tomoko; Yamagami, Hiroki; Sawa, Yoshihiko; Endo, Itsuro; Tsuneyama, Koichi; Matsumoto, Toshio; Tanaka, Eiji; Abe, Masahiro
• 出版事項: Japanese Society of Myeloma
• 出版年月日等: 2022
• 出版年（W3CDTF）: 2022
• 並列タイトル等: 内因性PP2A阻害因CIP2Aの過剰な発現は骨髄腫細胞の増殖・生存に極めて重要である; CIP2A-PP2A in myeloma
• タイトル（掲載誌）: International Journal of Myeloma
• 巻号年月日等（掲載誌）: 12 2
• 掲載巻: 12
• 掲載号: 2
• 掲載ページ: 14-23
• ISSN（掲載誌）: ISSN : 2187-3143
• 授与機関名: 徳島大学
• 授与年月日: 2022-05-12
• 報告番号: 甲第3640号
• 学位: 博士（歯学）
• 本文の言語コード: eng
• 件名標目: multiple myeloma; TAK1; CIP2A; PP2A
• 対象利用者: 一般
• 一般注記: The serine/threonine kinase TAK1 is constitutively overexpressed and auto-phosphorylated in multiple myeloma (MM) cells. Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase which dephosphorylates proteins phosphorylated by various serine/threonine kinases to regulate multiple cellular functions. We recently reported that the serine/threonine kinase TGF-β-activated kinase-1 (TAK1) is highly expressed and auto-phosphorylated to mediate critical growth and survival signaling in MM cells. We demonstrate here that regulation of PP2A activity inversely affects the phosphorylation levels of TAK1 in MM cells, and that MM cells aberrantly overexpress cancerous inhibitor of PP2A (CIP2A), an endogenous inhibitor for PP2A. CIP2A gene silencing as well as treatment with the CIP2A inhibitor TD52 potently induced MM cell death along with suppression of TAK1 expression in MM cells. These results suggest the critical role of PP2A inactivation via CIP2A upregulation in TAK1 phosphorylation and its protein expression and thereby MM cell growth and survival, posing the CIP2A-PP2A axis as an important therapeutic target.
• 一次資料へのリンクURL: fulltext; http://repo.lib.tokushima-u.ac.jp/files/public/11/117150/20220603152826216987/k3640_abstract.pdf; http://repo.lib.tokushima-u.ac.jp/files/public/11/117150/20220603152826332719/k3640_review.pdf; http://repo.lib.tokushima-u.ac.jp/files/public/11/117150/20220608152826187933/k3640_fulltext.pdf
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.57352/ijm.12.2_14
• 掲載誌（NCID）: AA12766965; https://ci.nii.ac.jp/ncid/AA12766965
• 連携機関・データベース: 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
• 提供元機関・データベース: 徳島大学 : 徳島大学機関リポジトリ