Organization
Graduate School of Medicine Program in Integrated Medicine Biological Chemistry Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Professor
SHIMADA Midori
Current Research Project and SDGs 1
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がんの治療標的に関する研究
Papers 49
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FOXO1 promotes cancer cell growth through MDM2-mediated p53 degradation
Tomiyasu, H; Habara, M; Hanaki, S; Sato, Y; Miki, Y; Shimada, M
CANCER SCIENCE Vol. 116 page： 232 - 232 2025.1
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Sato, Y; Habara, M; Hanaki, S; Masaki, T; Tomiyasu, H; Miki, Y; Sakurai, M; Morimoto, M; Kobayashi, D; Miyamoto, T; Shimada, M
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Vol. 121 ( 41 ) page： e2414618121 2024.10
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NFAT activation by FKBP52 promotes cancer cell proliferation by suppressing p53 Open Access
Hanaki, S; Habara, M; Tomiyasu, H; Sato, Y; Miki, Y; Masaki, T; Shibutani, S; Shimada, M
LIFE SCIENCE ALLIANCE Vol. 7 ( 8 ) 2024.8
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Calcineurin/NFATc1 pathway represses cellular cytotoxicity by modulating histone H3 expression Open Access
Sato, Y; Habara, M; Hanaki, S; Sharif, J; Tomiyasu, H; Miki, Y; Shimada, M
SCIENTIFIC REPORTS Vol. 14 ( 1 ) page： 14732 2024.6
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FOXO1 promotes cancer cell growth through MDM2-mediated p53 degradation Open Access
Tomiyasu, H; Habara, M; Hanaki, S; Sato, Y; Miki, Y; Shimada, M
JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 300 ( 4 ) page： 107209 2024.4
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Dephosphorylation of NFAT by Calcineurin inhibits Skp2-mediated degradation Open Access
Hanaki, S; Habara, M; Sato, Y; Tomiyasu, H; Miki, Y; Shibutani, S; Shimada, M
JOURNAL OF BIOCHEMISTRY Vol. 175 ( 3 ) page： 235 - 244 2024.3
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Calcineurin-mediated dephosphorylation enhances the stability and transactivation of c-Myc. Reviewed
Masaki T, Habara M, Hanaki S, Sato Y, Tomiyasu H, Miki Y, Shimada M.
Sci Rep. Vol. 13 ( 1 ) page： 13116 2023.8
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Impact of FKBP52 on cell proliferation and hormone-dependent cancers. Invited Reviewed
Hanaki S and Shimada M
Cancer Sci. Vol. 114 ( 7 ) page： 2729 - 2738 2023.4
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Dephosphorylation of the EGFR protein by calcineurin at serine 1046/1047 enhances its stability. Reviewed
2. Masaki T, Habara M, Shibutani S, Hanaki S, Sato Y, Tomiyasu H, Shimada M.
Biochem Biophys Res Commun. Vol. 641 page： 84 - 92 2023.1
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Estrogen receptor α revised: Expression, structure, function, and stability. Invited Reviewed
Habara M and Shimada M
Bioessays Vol. 44 ( 12 ) page： e2200148 2022.12
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FKBP52 and FKBP51 Differentially Regulate the Stability of Estrogen Receptor in Breast Cancer. Reviewed
Habara M, Sato Y, Goshima T, Sakurai M, Imai H, Shimizu H, Katayama Y, Hanaki S, Masaki T, Morimoto M, Nishikawa S, Toyama T, Shimada M.
Proc. Natl. Acad. Sci. U S A Vol. 119 ( 15 ) page： e2110256119 2022.4
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Decoding the Phosphatase Code: Regulation of Cell Proliferation by Calcineurin. Invited Reviewed
Masaki T and Shimada M
Int J Mol Sci. Vol. 23 ( 3 ) page： 1122 2022.1
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Calcineurin regulates the stability and activity of estrogen receptor α. Reviewed
Masaki T, Habara M, Sato Y, Goshima T, Maeda K, Hanaki S, Shimada M.
Proc. Natl. Acad. Sci. U S A. Vol. 118 ( 44 ) page： e2114258118 2021.11
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Targeting EZH2 as cancer therapy. Invited Reviewed
Hanaki S and Shimada M
J Biochem. Vol. 170 ( 1 ) page： 1 - 4 2021.9
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PP1 regulatory subunit NIPP1 regulates transcription of E2F1 target genes following DNA damage. Reviewed
Hanaki S, Habara M, Masaki T, Maeda K, Sato Y, Nakanishi M, Shimada M.
Cancer Sci. Vol. 112 ( 7 ) page： 2739 - 2752 2021.7
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FKBP51 and FKBP52 regulate androgen receptor dimerization and proliferation in prostate cancer cells. Reviewed
Maeda K, Habara M, Kawaguchi M, Matsumoto H, Hanaki S, Masaki T, Sato Y, Matsuyama H, Kunieda K, Nakagawa H,
Mol Oncol. Vol. 16 ( 4 ) page： 940 - 956 2021.2
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Phosphoglycerate mutase cooperates with Chk1 kinase to regulate glycolysis. Reviewed
Mikawa T, Shibata E, Shimada M, Ito K, Ito T, Kanda H, Takubo K, Lleonart ME, Inagaki N, Yokode M, Kondoh H.
iScience Vol. 23 ( 7 ) page： 101306 2020.7
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Calcineurin regulates cyclin D1 stability through dephosphorylation at T286. Reviewed
Goshima T, Habara M, Maeda K, Hanaki S, Kato Y, Shimada M.
Sci. Rep. Vol. 9 ( 1 ) page： 12779 2019.9
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Cdk1-mediated DIAPH1 phosphorylation maintains metaphase cortical tension and inactivates the spindle assembly checkpoint at anaphase. Reviewed
Nishimura K, Johmura Y, Deguchi K, Jiang Z, Uchida KSK, Suzuki N, Shimada M, Chiba Y, Hirota T, Yoshimura SH, Kono K, Nakanishi M
Nat. Commun. Vol. 10 ( 1 ) page： 981 2019.2
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The G2 checkpoint inhibitor CBP-93872 increases the sensitivity of colorectal and pancreatic cancer cells to chemotherapy. Reviewed
Iwata T, Uchino T, Koyama A, Johmura Y, Koyama J, Saito T, Ishiguro S, Arikawa T, Komatsu S, Miyachi M, Sano T, Nakanishi M, Shimada M.
PLOS ONE Vol. 12 ( 5 ) page： e0178221 2017.5
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Aurora B twists on histones for activation. Invited Reviewed
Shimada M, Nakanishi M
Cell Cycle. Vol. 15 ( 24 ) page： 3321 - 3322 2016.12
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Defective DNA repair increases susceptibility to senescence through extension of Chk1-mediated G2 checkpoint activation. Reviewed
Johmura Y, Yamashita E, Shimada M, Nakanishi K., Nakanishi M.
Sci. Rep. Vol. 6 page： 31194 2016.8
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Essential role of auto-activation circuitry on Aurora B-mediated H2AX-pS121 in mitosis. Reviewed
Shimada M, Goshima T, Matsuo H, Johmura Y, Haruta M, Murata K, Tanaka H, Ikawa M, Nakanishi K, Nakanishi M.
Nat Commun. Vol. 7 page： 12059 2016.7
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Activation of endogenous retroviruses in Dnmt1–/– ESCs involves disruption of SETDB1-mediated repression by NP95 binding to hemimethylated DNA. Reviewed
Sharif J, Endo A. T, Nakayama M, Karimi M. M, Shimada M, Katsuyama K, Goyal P, Brind'Amour J, Sun M, Sun Z, Ishikura T, Mizutani-Koseki Y, Ohara O, Shinkai Y, Nakanishi M, Xie H, Lorincz C. M*, Koseki H.
Cell Stem Cell Vol. 19 ( 1 ) page： 81 - 94 2016.7
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Loss of maintenance DNA methylation results in abnormal DNA origin firing during DNA replication. Reviewed
Haruta M, Shimada M*, Nishiyama A, Johmura Y, Le Tallec B, Debatisse M, Nakanishi M.
Biochem. Biophys. Res. Commun. Vol. 469 ( 4 ) page： 960 - 966 2016.1
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Physical interaction between MPP8 and PRC1 complex and its implication for regulation of spermatogenesis. Reviewed
Murata K, Sato S, Haruta M, Goshima T, Chiba Y, Takahashi S, Sharif J, Koseki H, Nakanishi M, Shimada M.
Biochem. Biophys. Res. Commun. Vol. 458 ( 3 ) page： 470 - 475 2015.3
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CBP-93872 inhibits NBS1-mediated ATR activation, abrogating maintenance of the DNA double strand break specific G2 checkpoint. Reviewed
Hirokawa T, Shiotani B, Shimada M, Murata K, Johmura Y, Haruta M, Tahara H, Takeyama H, Nakanishi M*:
Cancer Res. Vol. 74 ( 14 ) page： 3880 - 3889 2014.7
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Necessary and sufficient role for a mitosis skip in senescence induction. Reviewed
Johmura Y, Shimada M, Misaki T, Naiki-Ito A, Miyoshi H, Motoyama N, Ohtani N, Hara E, Nakamura M, Morita A, Takahashi S, Nakanishi M.
Mol. Cell Vol. 55 ( 1 ) page： 73 - 84 2014.7
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Mammal-specific H2A variant, H2ABbd, is involved in apoptotic induction via activation of NF-κB signaling pathway. Reviewed
1Goshima T, 1Shimada M (1Both authors contributed equally to this work), Sharif J, Matsuo H, Misaki T, Johmura Y, Murata K, Koseki H, Nakanishi M.
J Biol Chem. Vol. 289 ( 17 ) page： 11656 - 11666 2014.4
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Mitotic phosphorylation of MPP8 by cyclin-dependent kinases regulates chromatin dissociation Reviewed
Nishigaki M, Kawada Y, Misaki T, Murata K, Goshima T, Hirokawa T, Yamada C, Shimada M*, Nakanishi M.
Biochem. Biophys. Res. Commun. Vol. 432 ( 4 ) page： 654 - 659 2013.3
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Response to DNA damage: why do we need to focus on protein phosphatases? Invited Reviewed
Shimada M, Nakanishi M.
Front Oncol. Vol. 3 page： 8 2013.1
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Mechanisms of dNTP supply that play an essential role in maintaining genome integrity in eukaryotic cells. Invited Reviewed
Niida H, Shimada M, Murakami H and Nakanishi M.
Cancer Sci. Vol. 101 ( 12 ) page： 2505 - 2509 2010.12
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Protein phosphatase 1γ is responsible for dephosphorylation of histone H3 at Thr11 after DNA damage. Reviewed
Shimada M, Haruta M, Niida H, Sawamoto K, Nakanishi M.
EMBO Rep. Vol. 11 ( 11 ) page： 883 - 889 2010.11
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Cooperative functions of Chk1 and Chk2 reduce tumour susceptibility in vivo. Reviewed
Niida H, Murata K, Shimada M, Ogawa K, Ohta K, Suzuki K, Fujigaki H, Khaw AK, Banerjee B, Hande MP, Miyamoto T, Miyoshi I, Shirai T, Motoyama N, Delhase M, Appella E, Nakanishi M.
EMBO J. Vol. 29 ( 20 ) page： 3558 - 3570 2010.10
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Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase. Reviewed
Niida H, Katsuno Y, Sengoku M, Shimada M, Yukawa M, Ikura M, Ikura T, Kohno K, Shima H, Suzuki H, Tashiro S, Nakanishi M.
Genes Dev. Vol. 24 ( 4 ) page： 333 - 338 2010.2
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Chk1-cyclin A/Cdk1 axis regulates origin firing programs in mammals. Invited Reviewed
Nakanishi M, Katsuno Y, Niida H, Murakami H, Shimada M.
Chromosome Res. Vol. 18 ( 1 ) page： 103 - 113 2010.1
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DNA damage responses in skin biology—implications in tumor prevention and aging acceleration. Invited Reviewed
Nakanishi M, Niida H, Murakami H, Shimada M.
J. Dermatol. Sci. Vol. 56 ( 2 ) page： 76 - 81 2009.11
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Casein kinase II is required for the spindle assembly checkpoint by regulating Mad2p in fission yeast. Reviewed
Shimada M, Yamamoto A, Murakami-Tonami Y, Nakanishi M, Yoshida T, Aiba H, Murakami H.
Biochem Biophys Res Commun. Vol. 388 ( 3 ) page： 529 - 532 2009.10
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Ptpcd-1 is a novel cell cycle related phosphatase that regulates centriole duplication and cytokinesis. Reviewed
Zineldeen DH, Shimada M, Niida H, Katsuno Y and Nakanishi M.
Biochem Biophys Res Commun. Vol. 380 ( 3 ) page： 460 - 466 2009.3
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Cyclin A-Cdk1 regulates the origin firing program in mammalian cells. Reviewed
Katsuno Y, Suzuki A, Sugimura K, Okumura K, Zineldeen DH, Shimada M, Niida H, Mizuno T, Hanaoka F, Nakanishi M.
Proc Natl Acad Sci U S A. Vol. 106 ( 9 ) page： 3184 - 3189 2009.3
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Essential role of Chk1 in S phase progression through regulation of RNR2 expression. Reviewed
Naruyama H, Shimada M, Niida H, Zineldeen DH, Hashimoto Y, Kohri K and Nakanishi M.
Biochem. Biophys. Res. Commun. Vol. 374 ( 1 ) page： 79 - 83 2008.9
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Checkpoints meet the transcription at a novel histone milestone (H3-T11). Invited Reviewed
Shimada M, Nakanishi M.
Cell Cycle. Vol. 7 ( 11 ) page： 1555 - 1559 2008.6
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Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression Reviewed
Shimada M, Niida H, Zineldeen DH, Tagami H, Tanaka M, Saito H, Nakanishi M
CELL Vol. 132 ( 2 ) page： 221 - 232 2008.1
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Cdc2p controls the forkhead transcription factor Fkh2p by phosphorylation during sexual differentiation in fission yeast. Reviewed
Shimada M, Yamada-Namikawa C, Murakami-Tonami Y, Yoshida T, Nakanishi M, Urano T, Murakami H.
EMBO J. Vol. 27 ( 1 ) page： 132 - 142 2008.1
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Genetic instability in cancer cells by impaired cell cycle checkpoints. Invited Reviewed
Nakanishi M, Shimada M.
Cancer Sci. Vol. 97 ( 10 ) page： 984 - 989 2006.10
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DNA damage checkpoints and cancer. Invited Reviewed
Shimada M, Nakanishi M.
J. Mol. Histol. Vol. 37 page： 253 - 260 2006
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Regulation of Cdc2p and Cdc13p is required for cell cycle arrest induced by defective RNA splicing in fission yeast. Reviewed
Shimada M, Namikawa-Yamada C, Nakanishi M, Murakami H.
J. Biol. Chem., Vol. 280 ( 38 ) page： 32640 - 32648 2005.9
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The meiotic recombination checkpoint is regulated by checkpoint rad+ genes in fission yeast. Reviewed
Shimada M, Nabeshima K, Tougan T, Nojima H*
EMBO J Vol. 21 ( 11 ) page： 2807 - 2818 2002.6
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Replication factor C3 of Schizosaccharomyces pombe, a small subunit of replication factor C complex, plays a role in both replication and damage checkpoints. Reviewed
Shimada M, Okuzaki D, Tanaka S, Tougan T, Tamai KK, Shimoda C, Nojima H.
Mol. Biol. Cell, Vol. 10 ( 12 ) page： 3991 - 4450 1999.12
Books 3
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エピジェネティクス実験スタンダード Reviewed
島田 緑, 中西 真（ Role： Joint author , ヒストンのリン酸化、ユビキチン化活性測定法）
羊土社 2017
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がん基盤生物学 Reviewed
廣川 高久, 島田 緑, 竹山 廣光, 中西 真（ Role： Joint author , G2/M期チェックポイントを標的としたがん細胞特異的抗がん療法増強剤の開発）
南山堂 2013
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細胞周期フロンティア Reviewed
廣川 高久, 島田 緑, 竹山 廣光, 中西 真（ Role： Joint author , 細胞老化とチェックポイント）
共立出版 2010
MISC 19
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Impact of FKBP52 on cell proliferation and hormone-dependent cancers. Invited Reviewed
Hanaki S, Shimada M.
Cancer Sci. Vol. 114 ( 7 ) page： 2729 - 2738 2023.7
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みにれびゅう「ER陽性乳がんの新規治療法開発に向けたエストロゲン受容体制御メカニズムの解明」 Reviewed
羽原 誠, 島田 緑
生化学（日本生化学会） Vol. 95 page： 546 - 550 2023
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Estrogen receptor α revised: Expression, structure, function, and stability. Invited Reviewed
Habara M, Shimada M.
Bioessays. Vol. 44 ( 12 ) page： e2200148 2022.12
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Decoding the Phosphatase Code: Regulation of Cell Proliferation by Calcineurin. Invited Reviewed
Masaki T, Shimada M.
Int J Mol Sci. Vol. 23 ( 3 ) page： 1122 2022.1
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Targeting EZH2 as cancer therapy. Invited Reviewed
Hanaki S, Shimada M.
J Biochem. Vol. 170 ( 1 ) page： 1 - 4 2021.9
-
Aurora B twists on histones for activation. Invited Reviewed
Shimada M, Nakanishi M.
Cell Cycle. Vol. 15 ( 24 ) page： 3321 - 3322 2016.8
-
Response to DNA damage: why do we need to focus on protein phosphatases? Invited Reviewed
Shimada M, Nakanishi M.
Front Oncol. Vol. 3 ( 8 ) 2013.1
-
Mechanisms of dNTP supply that play an essential role in maintaining genome integrity in eukaryotic cells. Invited Reviewed
Niida H, Shimada M, Murakami H, Nakanishi M.
Cancer Sci. Vol. 101 ( 12 ) page： 2505 - 2509 2010.12
-
Chk1-cyclin A/Cdk1 axis regulates origin firing programs in mammals. Invited Reviewed
Nakanishi M, Katsuno Y, Niida H, Murakami H, Shimada M.
Chromosome Res. Vol. 18 ( 1 ) page： 103 - 113 2010.1
-
DNA damage responses in skin biology—implications in tumor prevention and aging acceleration. Invited Reviewed
Nakanishi M, Niida H, Murakami H, Shimada M.
J. Dermatol. Sci. Vol. 56 ( 2 ) page： 76 - 81 2009.11
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チェックポイントキナーゼChk1による転写制御とストレス応答 Reviewed
中西 真, 島田 緑
細胞工学（秀潤社） Vol. 28 page： 22 - 26 2009
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Checkpoints meet the transcription at a novel histone milestone (H3-T11). Invited Reviewed
Shimada M, Nakanishi M.
Cell Cycle. Vol. 7 ( 11 ) page： 1555 - 1559 2008.6
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DNA損傷反応とクロマチン修飾 Reviewed
島田 緑, 中西 真
細胞工学（秀潤社） Vol. 27 page： 1162 - 1167 2008
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Chk1の新しい機能-ヒストンH3-Thr11のリン酸化を介した転写制御機構 Reviewed
島田 緑, 中西 真
実験医学（羊土社） Vol. 26 page： 1740 - 1743 2008
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Genetic instability in cancer cells by impaired cell cycle checkpoints. Invited Reviewed
Nakanishi M, Shimada M, Niida H.
Cancer Sci. Vol. 97 ( 10 ) page： 984 - 989 2006.10
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DNA damage checkpoints and cancer. Invited Reviewed
Shimada M, Nakanishi M.
J. Mol. Histol. Vol. 37 page： 253 - 260 2006
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チェックポイントを制御するキナーゼ群 Reviewed
島田 緑, 中西 真
細胞工学（秀潤社） Vol. 25 page： 924 - 928 2006
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リン酸化修飾が明らかにした多彩な細胞周期チェックポイント機能 Reviewed
島田 緑, 村上 浩士, 中西 真
実験医学（羊土社） Vol. 23 page： 1999 - 2005 2005
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減数分裂期におけるチェックポイント機構 Reviewed
島田 緑, 野島 博
化学と生物（日本農芸化学会） Vol. 41 page： 84 - 91 2003
KAKENHI (Grants-in-Aid for Scientific Research) 2
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Gene expression by the three-dimensional histone code
Grant number：24K02227 2024.4 - 2027.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Authorship：Principal investigator
Grant amount：\18590000 （ Direct Cost: \14300000 、 Indirect Cost：\4290000 ）
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Decoding the histone code through higher-order structure
Grant number：21H02403 2021.4 - 2024.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Shimada Midori
Authorship：Principal investigator
Grant amount：\17290000 （ Direct Cost: \13300000 、 Indirect Cost：\3990000 ）
FKBP52 (FK506 Binding Protein 52) was identified as a poor prognostic factor for breast cancer. FKBP52 is a proline isomerase that isomerizes proline into cis and trans forms. It was found that FKBP52 enhances the function of estrogen receptor alpha (ERα), which is closely related to the malignant transformation of breast cancer. Of note, FKBP52 inhibition markedly inhibited breast cancer cell growth and destabilized ERα against endocrine treatment-resistant breast cancer cell lines, inhibiting their proliferation. Further analysis revealed that FKBP52 activates the expression of genes that promote proliferation via histone modifications.