Functional roles of transcription factor NF-E2 in megakaryocytic differentiation and platelet production

• Project/Area Number: 19390069
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: MOTOHASHI Hozumi Tohoku University, 大学院医学系研究科, 准教授 (00282351)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2008: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000); Fiscal Year 2007: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
• Keywords: 転写因子 / 巨核球 / 血小板 / 細胞分化 / 胞体突起形成 / NF-E2 / 転写複合体 / 蛋白質複合体 / マイクロアレイ / トランスジェニックマウス

Research Abstract

NF-E2は、巨核球の終末分化と血小板産生に必須の転写活性化因子である。 本研究において、NF-E2が、血小板の機能に関わる因子群を統一的に制御することを明らかにした。また、NF-E2は、酸化ストレス応答を誘導する転写因子Nrf2に対して競合的に作用することにより、巨核球内の活性酸素の蓄積を促進し、巨核球分化を促進することを見いだした。本研究の成果は、巨核球の分化・成熟の体内環境が、産生される血小板の活性化能に影響を与える可能性を示唆するものである

Research Products

• [Journal Article] 巨核球分化過程におけるストレス応答とその調節機構 (2009)
  • Author(s): 本橋ほづみ
  • Journal Title: 生化学 (印刷中)
  • NAID: 10025188147
  • Peer Reviewed
• [Journal Article] Physiological significance of reactive cysteine residues of Keap1 in determining Nrf2 activity (2008)
  • Author(s): Yamamoto, T., Suzuki, T., Kobayashi, A., Wakabayashi, J., Maher, J., Motohashi, H., and Yamamoto, M
  • Journal Title: Mol. Cell. Biol 28 Pages: 2758-2770
  • Peer Reviewed
• [Journal Article] Deletion of selenocysteine tRNA gene in macrophage and liver results in compensatory gene induction of cytoprotective enzymes by Nrf2 (2008)
  • Author(s): Suzuki, T., Kelly, V. P., Motohashi, H., Nakajima, O., Takahashi, S., Nishimura, S., and Yamamoto, M
  • Journal Title: J. Biol. Chem 283 Pages: 2021-2030
  • Peer Reviewed
• [Journal Article] Inducibility of cytochrome P450 1A1 and chemical carcinogenesis by benzo[a]pyrene in AhR repressor-deficient mice (2008)
  • Author(s): Hosoya, T., Harada, N., Mimura, J., Motohashi, H., Takahashi, S., Nakajima, O., Motita, M., Kawauchi, S., Yamamoto, M., and Fujii-Kuriyama, Y
  • Journal Title: Biochem. Biophys. Res. Commun 365 Pages: 562-567
  • Peer Reviewed
• [Journal Article] Physiological significance of reactive cysteine residues of Keapl in determining Nrf2 activity (2008)
  • Author(s): Yamamoto, T., Suzuki, T., Kobayashi, A., Wakabayashi, J., Maher, J., Motohashi, H., and Yamamoto, M.
  • Journal Title: Mol. Cell. Biol 28 Pages: 2758-2770
  • Peer Reviewed
• [Journal Article] Physiological significance of reactive cysteine residues of Keapl in determining Nrf2 activity. (2008)
  • Author(s): Yamamoto T, Suzuki T, Kobayashi A, Wakabayashi J, Maher J, Motohashi H, and Yamamoto M
  • Journal Title: Mol. Cell. Biol. 28 Pages: 2758-2770
  • Peer Reviewed
• [Journal Article] Deletion of selenocysteine tRNA gene in macrophage and liver results in compensatory gene induction of cytoprotective enzymes by Nrf2. (2008)
  • Author(s): Suzuki T, Kelly VP, Motohashi H, Nakajima O, Takahashi S, Nishimura S, and Yamamoto M
  • Journal Title: J. Biol. Chem. 283 Pages: 2021-2030
  • Peer Reviewed
• [Journal Article] Inducibility of cytochrome P450 1A1 and chemical carcinogenesis by benzo[a]pyrene in AhR repressor-deficient mice. (2008)
  • Author(s): Hosoya T, Harada N, Mimura J, Motohashi H, Takahashi S, Nakajima O, Motita M, Kawauchi S, Yamamoto M, and Fujii-Kuriyama Y
  • Journal Title: Biochem. Biophys. Res. Commun. 365 Pages: 562-567
  • Peer Reviewed
• [Journal Article] Nrf2 Neh5 domain is differentially utilized in the transactivation of cytoprotective genes (2007)
  • Author(s): Zhang, J., Hosoya, T., Maruyama, A., Nishikawa K., Maher, J.M., Ohta, T., Motohashi, H., Fukamizu, A., Shibahara, S., Itoh, K., and Yamamoto, M
  • Journal Title: Biochem. J 404 Pages: 459-466
  • Peer Reviewed
• [Journal Article] Molecular basis distinguishing the DNA binding profile of NRF2-MAF heterodimer from that of MAF homodimer. (2007)
  • Author(s): Kimura, M., Yamamoto, T., Zhang, J., Itoh, K., Kyo, M., Kamiya, T., Aburatani, H., Katsuoka, F., Kurokawa, H., Tanaka, T., Motohashi, H., and Yamamoto, M.
  • Journal Title: J.Biol.Chem 282 Pages: 33681-33690
  • Peer Reviewed
• [Journal Article] Carcinogenesis and transcriptional regulation through Maf recognition elements (2007)
  • Author(s): Motohashi, H., and Yamamoto, M.
  • Journal Title: Cancer Sci 98 Pages: 135-139
  • Peer Reviewed
• [Journal Article] 血小板形成を支える転写制御機構と血小板異常症 (2007)
  • Author(s): 本橋ほづみ
  • Journal Title: 実験医学 25 Pages: 1618-1623
  • Peer Reviewed
• [Journal Article] Molecular basis distinguishing the DNA binding profile of NRF2-MAF heterodimer from that of MAF homodimer. (2007)
  • Author(s): Kimura M, Yamamoto T, Zhang J, Itoh K, Kyo M, Kamiya T, Aburatani H, Katsuoka F, Kurokawa H, Tanaka T, Motohashi H^*, and Yamamoto M
  • Journal Title: J. Biol. Chem. 282 Pages: 33681-33690
  • Peer Reviewed
• [Journal Article] Nrf2 Neh5 domain is differentially utilized in the transactivation of cytoprotective genes. (2007)
  • Author(s): Zhang J, Hosoya T, Maruyama A, Nishikawa K, Maher JM, Ohta T, Motohashi H, Fukamizu A, Shibahara S, Itoh K and Yamamoto M
  • Journal Title: Biochem. J. 404 Pages: 459-466
  • Peer Reviewed
• [Journal Article] Carcinogenesis and transcriptional regulation through Maf recognition elements. (2007)
  • Author(s): Motohashi, H., and Yamamoto, M.
  • Journal Title: Cancer Sci. 98 Pages: 135-139
  • Peer Reviewed
• [Presentation] Gata1 gene hematopoietic regulatory domain directs functionally sufficient expression of NF-E2 p45 in megakaryocytes (2009)
  • Author(s): Motohashi, H., Takayama, M., Fujita, R., Katsuoka, F., Suzuki, M., and Yamamoto, M
  • Organizer: Gordon Research Conference on Cell Bioligy of Megakaryocytes & Platelets
  • Place of Presentation: Galveston, Texas
• [Presentation] NF-E2 p45 N-terminal region is essential for transactivation mediating terminal differentiation of megakaryocytes (2009)
  • Author(s): Takayama, M., Motohashi, H., Ikura, T., Igarashi, K., and Yamamoto, M
  • Organizer: Molecular mechanism of environmental response to food and oxygen III
  • Place of Presentation: Gonryo-kaikan in Tohoku University, Sendai, Japan
• [Presentation] Gata1 hematopoietic regulatory domain directs sufficient expression of NF-E2 p45 in megakaryocytes (2009)
  • Author(s): Fujita, R., Takayama, M., Motohashi, H., and Yamamoto, M
  • Organizer: Molecular mechanism of environmental response to food and oxygen III
  • Place of Presentation: Gonryo-kaikan in Tohoku University, Sendai, Japan
• [Presentation] Gatal gene hematopoietic regulatory domain directs functionally sufficient expression of NF-E2 p45 in megakaryocytes (2009)
  • Author(s): Motohashi H, Takayama M, Fujita R, Katsuoka F, Suzuki M and Yamamoto M.
  • Organizer: Gordon Research Conference on Cell Bioligy of Megakarvocytes & Platelets.
  • Place of Presentation: Galveston, Texas, USA
• [Presentation] 巨核球分化と転写因子NF-E2による酸化ストレス蓄積プログラム. 第31回日本分子生物学会年会 (2008)
  • Author(s): 本橋ほづみ, 高山昌理子, 藤田理恵, 勝岡史城, 山本雅之
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド.
• [Presentation] 巨核球における転写因子NF-E2 p45の転写調節機構 (2008)
  • Author(s): 高山昌理子, 井倉毅, 五十嵐和彦, 山本雅之, 本橋ほづみ
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] NF-E2 p45欠失マウスの巨核球系のトランスジェニックレスキュー解析 (2008)
  • Author(s): 藤田理恵, 高山昌理子, 本橋ほづみ, 山本雅之
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] S-Guanylation proteomics : NOと活性酸素に依存したユニークなチオール基翻訳後修飾 (2008)
  • Author(s): 澤智裕, 藤井重元, 入江厚, 岡本竜哉, 居原秀, 本橋ほづみ, 山本雅之, 赤池孝章
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] 新規環状ヌクレオチド8-ニトログアノシン3',5'-環状1リン酸による転写制御因子Keap1のS-グアニル化とその酸化ストレス応答における役割 (2008)
  • Author(s): 藤井重元, 澤智裕, 岡本竜哉, 居原秀, 本橋ほづみ, 山本雅之, 赤池孝章.
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] 小Maf群因子3重欠損細胞レスキュー系の確立と同系を用いた小Maf群因子の機能解析 (2008)
  • Author(s): 勝岡史城, 中山博未, 本橋ほづみ, 山本雅之
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] 血小板分化におけるプロリン異性化控訴Pin1の機能解析 (2008)
  • Author(s): 鈴木伸幸, 小野栄夫, 北沢博, 本橋ほづみ, 原田彰宏, 秋山弘匡, 内田隆史
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] NO依存的なニトロ化ヌクレオチド、8-ニトログアノシン3', 5'-環状1リン酸の精製を介したKeap1チオール基の修飾 (2008)
  • Author(s): 澤智裕, 藤井重元, 入江厚, 岡本竜哉, 本橋ほづみ, 山本雅之, 赤池孝章
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場.
• [Presentation] NF-E2 enhances accumulation of reactive exygen species and promotes megakaryocytic terminal differentiation (2008)
  • Author(s): Motohashi, H., Takayama, M., Fujita, R., Katsuoka, F., and Yamamoto, M
  • Organizer: 16th Conference on Hemoglobin Switching, Asilomar Conference Center
  • Place of Presentation: Monterey, California
• [Presentation] Physiological role of Keap1 S-guanylation by 8-nitroguanosine 3',5'-cyclic monophosphate formed in C6 glioma cells. Fifth International Conference Biology, Chemistry and Therapeutic Applications of Nitric Oxide (2008)
  • Author(s): Fujii, S., Sawa, T., Okamoto, T., Ihara, H., Motohashi, H., Yamamoto, M., and Akaike, T
  • Organizer: Festspielhaus Bregenz
  • Place of Presentation: Austria
• [Presentation] Nitric oxide-dependent sulfhydryl modification of Keap1 by 8-nitroguanosine 3',5'-cyclic monophosphate (2008)
  • Author(s): Sawa, T., Fujii, S., Irie, A., Okamoto, T., Motohashi, H., Yamamoto, M., and Akaike, T
  • Organizer: Fifth International Conference Biology, Chemistry and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Festspielhaus Bregenz, Austria
• [Presentation] Crystal structure of MafG in complex with iys cognate DNA (2008)
  • Author(s): Kurokawa, H., Sueno, S., Kimura, M., Motohashi, H., Yamamoto, M., and Tanaka, T
  • Organizer: The 21st Naito conference on Nuclear Dynamics and RNA [I]
  • Place of Presentation: Yatsugatake
• [Presentation] Crystal structure of MafG in complex with iys cognate DNA (2008)
  • Author(s): Kurokawa H, Sueno S, Kimura M, Motohashi H, Yamamoto M, and Tanaka T.
  • Organizer: The 21^<st> Naito conference on Nuclear Dynamics and RNA [I],
  • Place of Presentation: Yatsugatake, Japan
• [Presentation] Physiological role of Keapl S-guanylation by 8-nitroguanosine 3', 5'-cyclic monophosphate formed in C6 glioma cells (2008)
  • Author(s): Fujii S, Sawa T, Okamoto T, Ihara H, Motohashi H, Yamamoto M. and Akaike T
  • Organizer: Fifth International Conference Biology, Chemistry and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Festspielhaus Bregenz, Austria
• [Presentation] Nitric oxide-dependent sulfhydryl modification of Keapl by 8-nitroguanosine 3', 5'-cyclic monophosphate (2008)
  • Author(s): Sawa T, Fujii S, Irie A, Okamoto T, Motohashi H, Yamamoto M. and Akaike T
  • Organizer: Fifth International Conference Biology, Chemistry and Therapeutic Applications of Nitric Oxide.
  • Place of Presentation: Festspielhaus Bregenz, Austria
• [Presentation] NF-E2 enhances accumulation of reactive exygen species and promotes megakaryocytic terminal differentiation (2008)
  • Author(s): Motohashi H, Takayama M, Fujita R, Katsuoka F, and Yamamoto M
  • Organizer: 16^<th> Conference on Hemoglobin Switching
  • Place of Presentation: Asilomar Conference Center, Monterey, California, USA
• [Presentation] NO依存的なニトロ化ヌクレオチド、8-ニトログアノシン3', 5'-環状1リン酸の精製を介したKeaplチオール基の修飾 (2008)
  • Author(s): 澤智裕, 藤井重元, 入江厚, 岡本竜哉, 本橋ほづみ, 山本雅之, 赤池孝章
  • Organizer: 第67回日本癌学会学術総会.
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 巨核球分化と転写因子NF-E2による酸化ストレス蓄積プログラム. (2008)
  • Author(s): 本橋ほづみ, 高山昌理子, 藤田理恵, 勝岡史城, 山本雅之
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] NF-E2 p45欠失マウスの巨核球系のトランスジェニックレスキュー解析 (2008)
  • Author(s): 藤田理恵, 高山昌理子, 本橋ほづみ, 山本雅之.
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド.
• [Presentation] 新規環状ヌクレオチド8-ニトログアノシン3', 5'-環状1リン酸による転写制御因子KeaplのS-グアニル化とその酸化ストレス応答における役割 (2008)
  • Author(s): 藤井重元, 澤智裕, 岡本竜哉, 居原秀, 本橋ほづみ, 山本雅之, 赤池孝章
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] 血小板分化におけるプロリン異性化控訴Pinlの機能解析 (2008)
  • Author(s): 鈴木伸幸, 小野栄夫, 北沢博, 本橋ほづみ, 原田彰宏, 秋山弘匡, 内田隆史.
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] Clara-cell specific keap1 conditional knockout mice have strong Nrf2 activation but are sensitive to bleomycin-induced lung injury (2007)
  • Author(s): Maher, J., Suzuki, T., Taguchi, K., Kawatani, Y., Motohashi, H., Ishii, Y., Yamamoto, M
  • Organizer: The 2nd JST-ERATO Environmental Response Project International Symposium on "The Environmental Response" in Tsukuba
  • Place of Presentation: Japan
• [Presentation] Small Maf proteins are required for the stable nuclear localization of Nrf2 (2007)
  • Author(s): Katsuoka, F., Nakayama, H., Motohashi, H., and Yamamoto, M.
  • Organizer: The 2nd JST-ERATO Environmental Response Project International Symposium on "The Environmental Response" in Tsukuba
  • Place of Presentation: Japan
• [Presentation] Molecular basis distinguishing the DNA binding profile of NRF2-MAF heterodimer from that of MAF homodimer (2007)
  • Author(s): Kimura, M., Yamamoto, T., Zhang, J., Itoh, K., Katsuoka, F., Tanaka, T., Motohashi, H., and Yamamoto, M
  • Organizer: The 2nd JST-ERATO Environmental Response Project International Symposium on "The Environmental Response" in Tsukuba
  • Place of Presentation: Japan
• [Presentation] Deciphering key reactive cysteines that determine Nrf2 activation in vivo (2007)
  • Author(s): Suzuki, T., Yamamoto, T., Kobayashi, A., Wakabayashi, J., Maher, J., Motohashi, H., and Yamamoto, M
  • Organizer: The 2nd JST-ERATO Environmental Response Project International Symposium on "The Environmental Response" in Tsukuba
  • Place of Presentation: Japan
• [Presentation] c-Myb regulates CD9 gene expression during megakaryopoiesis (2007)
  • Author(s): Mukai, H.Y., Kono, T., Motohashi, H., Kojima, H., and Yamamoto, M
  • Organizer: 49th ASH Annual Meeting and Exposition. Atlanta
  • Place of Presentation: Georgia, USA
• [Presentation] Maf認識配列に依存する転写制御の巨核球分化に対する貢献 (2007)
  • Author(s): 木村桃子, 山本雅之, 本橋ほづみ
  • Organizer: 第30回日本分子生物学会年会・第80回に本生化学会大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Mafホモ2量体とMaf-CNCへテロ2量体によるDNA認識様式の違いの分子基盤とその生物学的重要性の検討 (2007)
  • Author(s): 本橋ほづみ, 木村桃子, 京基樹, 伊東健, 勝岡史城, 山本雅之
  • Organizer: 第30回日本分子生物学会年会・第80回に本生化学会大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Nrf2の核安定局在化における小Maf群因子の重要性の検討 (2007)
  • Author(s): 勝岡史城, 中山博未, 本橋ほづみ, 山本雅之
  • Organizer: 第30回日本分子生物学会年会・第80回に本生化学会大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Clara-cell specific keap1 conditional knockout mice have strong Nrf2 activation but are sensitive to bleomycin-induced lung injury (2007)
  • Author(s): Maher, J., Suzuki, T., Taguchi, K., Kawatani, Y., Motohashi, H., Ishii, Y., Yamamoto, M
  • Organizer: 8th International ISSX meeting
  • Place of Presentation: Sendai
• [Presentation] 転写因子c-mybによる巨核球造血制御 (2007)
  • Author(s): 向井陽美,本橋ほづみ,長澤俊郎,山本雅之
  • Organizer: 第5回幹細胞シンポジウム
  • Place of Presentation: 淡路島
• [Presentation] The critical function of c-myb and its related genes on megakaryopoiesis (2007)
  • Author(s): Mukai, H.Y., Motohashi, H., Nagasawa, T., and Yamamoto, M
  • Organizer: Gordon Research Conference on Cell Biology of Megakaryocytes and Platelets
  • Place of Presentation: Ventura, CA, USA
• [Presentation] Mafホモ2量体とMaf-CNCヘテロ2量体によるDNA認識様式の違いの分子基盤とその生物学的重要性の検討. (2007)
  • Author(s): 本橋ほづみ, 木村桃子, 京基樹, 伊東健, 勝岡史城, 山本雅之.
  • Organizer: 第30回日本分子生物学会年会・第80回に本生化学会大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Maf認識配列に依存する転写制御の巨核球分化に対する貢献. (2007)
  • Author(s): 木村桃子, 山本雅之, 本橋ほづみ.
  • Organizer: 第30回日本分子生物学会年会・第80回に本生化学会大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Nrf2の核安定局在化における小Maf群因子の重要性の検討. (2007)
  • Author(s): 勝岡史城, 中山博未, 本橋ほづみ, 山本雅之.
  • Organizer: 第30回日本分子生物学会年会・第80回に本生化学会大会
  • Place of Presentation: パシフィコ横浜