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Bibliographic Record
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- Material Type
- 文書・図像類
- Author/Editor
- 叶内, 宏明
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- Alternative Title
- Fundamental studies for development of a novel anti-tumor drug based on perchloric acid-soluble protein
- Text Language Code
- jpn
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- 一般
- Note (General)
- 2011-2013年度科学研究費助成事業(挑戦的萌芽研究)研究成果報告書 課題番号:24658244 研究代表者:叶内宏明(鹿児島大学・獣医学部・准教授)過塩素酸可溶性蛋白質(PSP)は細胞増殖を抑制する。しかしPSPは増殖中の細胞にも存在しており、矛盾がある。ラット肝部分切除後に起こる細胞増殖の過程で3量体の割合が減少した。肝重量が切除前にまで戻ると再び三量体の割合が増えた。増殖時のPSPは高次構造が変化し、3量体でないPSPは細胞増殖を抑制する性質を持たない可能性が推測された。3量体を形成していない時期にPSPと結合する蛋白質を見いだした。PSPの転写開始および調節に必要な配列を明らかにし、PSPの発現を誘導する2種類の化合物を見いだした。これらの化合物は新規な抗がん剤の候補となった。Perchloric acid-soluble protein (PSP) has an anti-proliferating activity. Its activity seems to be suppressed in cells, because the PSP exists in proliferating cells. Crystal structural analysis of PSP shows that PSP exist as a homo-trimer. Our preliminary experiment, however, suggested PSP existed not only timer but also monomer or dimer. To elucidate that changing higher-order protein structure of PSP is related to cell proliferation, we evaluated the state of higher-order protein structure of PSP during liver regeneration after partial hepatectomy in rats. As a result, PSP existed as trimer in normal liver, but the ratio of trimer of PSP decreased after hepatectomy and the ration of monomer or dimer of PSP increased until liver weight returned to the intact weight. It is suspected monomer or dimer PSP not to suppress cell proliferation. Additionally, we identified the DNA position for expression and regulation of PSP mRNA. We identified two molecules to induce PSP expression.