Dictyostelium Differentiation-Inducing Factor-1 Binds to Mitochondrial Malate Dehydrogenase and Inhibits Its Activity
スポンサーリンク
概要
- 論文の詳細を見る
We have reported that the differentiation-inducing factors (DIFs) DIF-1 and DIF-3, morphogens secreted from Dictyostelium discoideum, inhibit proliferation of several cancer cells via suppression of the Wnt/β-catenin signaling pathway. However, the target molecules of DIFs involved in the anti-proliferative effects are still unknown. In the present study, DIF-1–tethered resins were synthesized to explore the target molecules of DIFs, and mitochondrial malate dehydrogenase (mMDH) was identified as one of the target molecules. In the in vitro assay, DIF-1 and other analogs including 2-MIDIF-1, DIF-3, and 6-MIDIF-3 were found to be capable of binding to mMDH but not to cytoplasmic MDH. However, only DIF-1 and 2-MIDIF-1 inhibited the enzymatic activity of mMDH. The effects of DIF analogs on ATP content and cell proliferation were then analyzed using HeLa cells. DIF-1 and 2-MIDIF-1 were found to lower the ATP content and both chemicals inhibited HeLa cell proliferation, suggesting that inhibition of mMDH activity affected cell energy production, probably leading to the inhibition of proliferation. These results suggest that the inhibition of mMDH activity by DIF-1 and 2-MIDIF-1 could be one of the mechanisms to induce anti-proliferative effects, independent of the inhibition of the Wnt/β-catenin signaling pathway.
著者
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Miwa Yoshikazu
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University
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Sasaguri Toshiyuki
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University
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WATANABE Yutaka
Department of Machine Intelligence and Systems Engineering, Graduate School of Engineering, Tohoku U
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Mitsuhashi Takeshi
Department Of Cardiovascular Medicine Shinshu University Graduate School Of Medicine
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Maruyama Takao
Department Of Internal Medicine And Molecular Science Osaka University Graduate School Of Medicine
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Tsushima Motoo
Department Of Internal Medicine Keio University School Of Medicine
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Maruyama C
Department Of Food And Nutrition Japan Women's University
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Maruyama Taro
九州大学 医学研究院臨床薬理学
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Maruyama Chizuko
日本女子大学 家政学部食物学科
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Maruyama Chizuko
Department Of Food And Nutrition Japan Women's University
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Maenaka Katsumi
Medical Institute Of Bioregulation Kyushu University
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Maenaka Katsumi
Medical Inst. Of Bioregulation Kyushu Univ. Jpn
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Morimoto Sachio
Department Of Clinical Pharmacology Faculty Of Medical Science Kyushu University
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Matsuda Tomoko
Department Of Physiology Gifu University School Of Medicine
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Matsuda Tomoko
Dep. Of Clinical Pharmacology Fac. Of Medical Sciences Kyushu Univ. Jpn
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Matsuda Tomoko
Department Of Materials Chemistry Ryukoku University
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Takahashi-yanaga Fumi
Dep. Of Clinical Pharmacology Fac. Of Medical Sciences Kyushu Univ. Jpn
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HIRATA Masato
Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collabo
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Miwa Yoshikazu
Department Of Clinical Pharmacology Faculty Of Medical Sciences Kyushu University
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Takahashi-Yanaga Fumi
Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University
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Watanabe Yutaka
Department Of Epidemiology For Community Health And Medicine Kyoto Prefectural University Of Medicin
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Hirata Masato
Laboratory Of Molecular And Cellular Biochemistry Faculty Of Dental Science And Station For Collabor
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Yoshihara Tatsuya
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Japan
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Kubohara Yuzuru
Biosignal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, Japan
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Matsushita Takashi
Department Of Cardiovascular Medicine Shinshu University Graduate School Of Medicine
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Sasaguri Toshiyuki
Department Of Clinical Pharmacology Faculty Of Medical Sciences Kyushu University
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Matsuda Tomoko
Department Of Bioengineering Tokyo Institute Of Technology
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Kubohara Yuzuru
Biosignal Research Center Institute For Molecular And Cellular Regulation Gunma University
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Watanabe Yutaka
Department Of Cardiology Otsu Red Cross Hospital
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Watanabe Yutaka
Department Of Applied Chemistry Faculty Of Engineering Ehime University
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Yoshihara Tatsuya
Department Of Clinical Pharmacology Faculty Of Medical Sciences Kyushu University
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WATANABE Yutaka
Department of Anatomy, Osaka Medical College
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Takahashi-Yanaga Fumi
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Japan
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Miwa Yoshikazu
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Japan
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Matsuda Tomoko
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Japan
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Morimoto Sachio
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Japan
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Hirata Masato
Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Sciences, Kyushu University, Japan
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Maenaka Katsumi
Medical Institute of Bioregulation, Kyushu University, Japan
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Sasaguri Toshiyuki
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Japan
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Watanabe Yutaka
Department of Applied Chemistry, Faculty of Engineering, Ehime University, Japan
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