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

• Material Type: 博士論文
• Title: Aberrant upregulation of the endogenous PP2A inhibitor CIP2A is vital for myeloma cell growth and survival
• Author/Editor: 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
• Author Heading: 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
• Publication, Distribution, etc.: Japanese Society of Myeloma
• Publication Date: 2022
• Publication Date (W3CDTF): 2022
• Alternative Title: 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
• Periodical title: International Journal of Myeloma
• No. or year of volume/issue: 12 2
• Volume: 12
• Issue: 2
• Pages: 14-23
• ISSN (Periodical Title): ISSN : 2187-3143
• Degree grantor/type: 徳島大学
• Date Granted: 2022-05-12
• Dissertation Number: 甲第3640号
• Degree Type: 博士（歯学）
• Text Language Code: eng
• Subject Heading: multiple myeloma; TAK1; CIP2A; PP2A
• Target Audience: 一般
• Note (General): 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.
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.57352/ijm.12.2_14
• 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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http://repo.lib.tokushima-u.ac.jp/files/public/11/117150/20220603152826216987/k3640_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/117150/20220603152826332719/k3640_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/117150/20220608152826187933/k3640_fulltext.pdf fulltext