Involvement of lipid-metabolizing enzymes in stress response

• Project/Area Number: 23659033
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: ICHIJO Hidenori 東京大学, 大学院・薬学系研究科, 教授 (00242206)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ASK1 / 脂質 / ストレス応答 / シグナル伝達 / 線虫 / 緑膿菌感染 / MAP キナーゼ / MAPキナーゼ

Research Abstract

To analyze ASK family-dependent stress signaling, we identified 55 candidate ASK activator candidates by a genome-wide RNAi screening in C. elegans. Those candidates were further analyzed in the context of neuronal differentiation, innate immunity and oxidative stress response. Finally, we identified gene X as an activator of ASK1 by comparing it with known p38signaling components.

Research Products

• [Journal Article] Involvement of ASK1-p38 pathway in the pathogenesis of diabetes triggered by pancreatic s cell exhaustion (2013)
  • Author(s): Yamaguchi, K., Takeda, K., Kadowaki, H., Ueda, I., Namba, Y., Ouchi, Y. Nishitoh, H. and Ichijo, H.
  • Journal Title: Biochim. Biophys. Acta. Volume: 1830 Issue: 6 Pages: 3656-3663
  • DOI: 10.1016/j.bbagen.2013.01.029
  • Peer Reviewed
• [Journal Article] Apoptosis Signal-regulating Kinase 1 deficiency attenuates vascular injury-induced neointimal hyperplasia by suppressing apoptosis in smooth muscle cells. (2013)
  • Author(s): Tasaki, T., *Yamada, S., Guo, X., Tanimoto, A., Wang, K-T., Nabeshima, A., Kitada, S., Noguchi H., Kimura, S., Shimajiri, S., Kohno, K., Ichijo, H. and Sasaguri, Y.
  • Journal Title: Am. J. Pathol. Volume: 182 Issue: 2 Pages: 597-609
  • DOI: 10.1016/j.ajpath.2012.10.008
  • Peer Reviewed
• [Journal Article] Activation mechanisms of ASK1 in response to various stresses and its significance in intracellular signaling (2013)
  • Author(s): Shiizaki, S., Naguro, I. and Ichijo, H.
  • Journal Title: Adv. Biol. Regul. Volume: 53 Issue: 1 Pages: 135-144
  • DOI: 10.1016/j.jbior.2012.09.006
  • Peer Reviewed
• [Journal Article] Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury. (2013)
  • Author(s): Katome, T., Namekata, K., Guo, X., Semba, K., Kittaka, D., Kawamura, K., Kimura, A., Harada, C., Ichijo, H., Mitamura, Y. and Harada, T.
  • Journal Title: Cell Death Differ. Volume: 20 Issue: 2 Pages: 270-280
  • DOI: 10.1038/cdd.2012.122
  • Peer Reviewed
• [Journal Article] Integration of the Apoptosis signal-regulating kinase 1-mediated stress signaling with the Akt/PKB-IκB kinase cascade (2013)
  • Author(s): Puckett, M.C. et al.
  • Journal Title: Mol.Cell. Biol., Volume: in press
  • Peer Reviewed
• [Journal Article] ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney. (2012)
  • Author(s): Naguro I., et al.
  • Journal Title: Nature Communications Volume: 3 Issue: 1 Pages: 1285-1285
  • DOI: 10.1038/ncomms2283
  • Peer Reviewed
• [Journal Article] Apoptosis signal- regulating kinase-1 inhibitor as a potent therapeutic drug for the treatment of gastric cancer (2012)
  • Author(s): Hayakawa, Y., Hirata, Y., Sakitani, K., Nakagawa, H., Nakata, W., Kinoshita, H., Takahashi, R., Takeda, K., Ichijo, H., Maeda1, S. and Koike, K
  • Journal Title: Cancer Sci Volume: 103 Pages: 2181-2185
  • Peer Reviewed
• [Journal Article] The kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5 (2012)
  • Author(s): Yusuke Sekine, Ryo Hatanaka, Takeshi Watanabe. Naoki Sono, Shun-ichiro Iemura, Tohru Natsume, Erina Kuranaga, Masayuki Miura, Kohsuke Takeda, and Hidenori Ichijo
  • Journal Title: Molecular Cell Volume: 48 Issue: 5 Pages: 1-13
  • DOI: 10.1016/j.molcel.2012.09.018
  • NAID: 120007150217
  • Peer Reviewed
• [Journal Article] Rhomboid protease PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM5 (2012)
  • Author(s): Sekine, S., et al.
  • Journal Title: J. Biol. Chem. Volume: 287 Issue: 41 Pages: 34635-34645
  • DOI: 10.1074/jbc.m112.357509
  • Peer Reviewed
• [Journal Article] Therapeutic targets in the ASK1-dependent stress signaling pathways (2012)
  • Author(s): Hayakawa, R., Hayakawa, T., Takeda, K. and Ichijo, H.
  • Journal Title: Proceedings of the Japan Academy, Series B Volume: 88 Issue: 8 Pages: 434-453
  • DOI: 10.2183/pjab.88.434
  • NAID: 130001924759
  • ISSN: 0386-2208, 1349-2896
  • Peer Reviewed
• [Journal Article] The Phosphorylation-Dependent Regulation of Mitochondrial Proteins in Stress Responses (2012)
  • Author(s): Kanamaru, Y., Sekine S., Ichijo, H. and Takeda, K.
  • Journal Title: J. Signal Transduc. Volume: 2012 Pages: 12-12
  • DOI: 10.1155/2012/931215
  • Peer Reviewed
• [Journal Article] ASK1 promotes apoptosis of normal and malignant plasma cells. (2012)
  • Author(s): Lin, F.R., Huang, S.Y., Hung, K.H., Su, S.T., Chung, C.H., Matsuzawa, A., Hsiao, M., Ichijo, H. and Lin, K.I.
  • Journal Title: Blood Volume: 120 Issue: 5 Pages: 1039-1047
  • DOI: 10.1182/blood-2011-12-399808
  • Peer Reviewed
• [Journal Article] Oxidative Stress-Induced Diseases via the ASK1 Signaling Pathway (2012)
  • Author(s): Soga, M., Matsuzawa, A., Ichijo, H.
  • Journal Title: Int. J. Cell Biol. Volume: 2012 Pages: 439587-439587
  • DOI: 10.1155/2012/439587
  • Peer Reviewed
• [Journal Article] A novel monoclonal antibody reveals a conformational alteration shared by amyotrophic lateral sclerosis-linked SOD1 mutants. (2012)
  • Author(s): Fujisawa, T., Homma, K., et al.
  • Journal Title: Ann Neurol Volume: 72 Issue: 5 Pages: 739-749
  • DOI: 10.1002/ana.23668
  • Peer Reviewed
• [Journal Article] Novel mechanism of angiotensin II-induced cardiacinjury in hypertensive rats : the critical role of ASK1 (2012)
  • Author(s): Nako, H., et al.
  • Journal Title: Hypertens.Res. Volume: 35 Issue: 2 Pages: 194-200
  • DOI: 10.1038/hr.2011.175
  • Peer Reviewed
• [Journal Article] Prevention of apoptosis by mitochondrial phosphatase PGAM5 in the mushroom body is crucial for heat shock resistance in Drosophila melanogaster (2012)
  • Author(s): Ishida, Y., et al.
  • Journal Title: PloS ONE Volume: 7 Issue: 2 Pages: 3006-3016
  • DOI: 10.1371/journal.pone.0030265
  • Peer Reviewed
• [Journal Article] Apoptosis Signal-Regulating Kinase 1 Mediates MPTP Toxicity and Regulates Glial Activation (2012)
  • Author(s): Lee, K.W.
  • Journal Title: PloS ONE Volume: 7 Issue: 1 Pages: e29935-e29935
  • DOI: 10.1371/journal.pone.0029935
  • Peer Reviewed
• [Journal Article] ER stress activates the NLRP3 inflammasome via an UPR-independent pathway (2012)
  • Author(s): P. Menu, A. Mayor, R. Zhou, A. Tardivel, H. Ichijo, K. Mori and J. Tschopp
  • Journal Title: Cell Death Dis. Volume: 3 Issue: 1 Pages: e261-e261
  • DOI: 10.1038/cddis.2011.132
  • Peer Reviewed
• [Journal Article] Deletion of apoptosis signal regulating kinase-1 prevents ventilatorinduced lung injury in mice (2012)
  • Author(s): Makena, P.S., et al.
  • Journal Title: Am.J.Respir.Cell Mol.Biol Volume: (in press) Issue: 4 Pages: 461-469
  • DOI: 10.1165/rcmb.2011-0234oc
  • Peer Reviewed
• [Journal Article] Therapeutic targets in the ASK1-dependent stress signalling pathways (2012)
  • Author(s): Hayakawa, R. et al.
  • Journal Title: Proc. Jpn. Acad. Ser. B: Phys. Biol. Sci. Volume: 88 Pages: 434-453
  • Peer Reviewed
• [Journal Article] Apoptosis signal-regulating kinase-1 inhibitor as a potent therapeutic drug for the treatment of gastric cancer. (2012)
  • Author(s): Hayakawa, Y., Hirata, Y., Sakitani, K., Nakagawa, H., Nakata, W., Kinoshita, H., Takahashi, R., Takeda, K., Ichijo, H., Maeda1, S. and Koike, K.
  • Journal Title: Cancer Sci. Volume: 103 Issue: 12 Pages: 2181-2185
  • DOI: 10.1111/cas.12024
  • Peer Reviewed
• [Journal Article] HSV infection induces production of ROS which potentiate signaling from pattern recognition receptors : role for S-gluta hionylation of TRAF3 and 6 (2011)
  • Author(s): Dosal, RG.
  • Journal Title: PLoS Pathogens Volume: 7 Issue: 9 Pages: e1002250-e1002250
  • DOI: 10.1371/journal.ppat.1002250
  • Peer Reviewed
• [Journal Article] Apoptosis Signal-Regulating Kinase 1 Deficiency Accelerates Hyperlipidemia-Induced Atheromatous Plaques via Suppression of Macrophage Apoptosis (2011)
  • Author(s): Yamada, S.
  • Journal Title: Arterioscler.Thromb.Vasc.Biol. Volume: 31 Issue: 7 Pages: 1555-1564
  • DOI: 10.1161/atvbaha.111.227140
  • Peer Reviewed
• [Journal Article] p38 MAP kinase regulates the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors (2011)
  • Author(s): Sekine,Y., Takagahara,S., Hatanaka, R., Watanabe, T., Oguchi, H., Noguchi, T., Naguro, I., Kobayashi, K., Tsunoda, M., Funatsu, T., Nomura, H., Toyoda, T., Matsuki, N., Kuranaga, E., Miura, M., Takeda, K., and Ichijo, H.
  • Journal Title: J. Cell Sci. Volume: 124 Issue: 17 Pages: 3006-3016
  • DOI: 10.1242/jcs.085902
  • Peer Reviewed
• [Journal Article] Apoptosis signal-regulating kinase 1 inhibits hepatocarcinogenesis by controlling the tumor-suppressing function of stress-activated MAPK (2011)
  • Author(s): Nakagawa, H.
  • Journal Title: Hepatology Volume: 54 Issue: 1 Pages: 185-195
  • DOI: 10.1002/hep.24357
  • Peer Reviewed
• [Presentation] 細胞がストレスを感じる仕組みと疾患 (2013)
  • Author(s): 一條秀憲
  • Organizer: 第37回皮膚科免疫セミナー
  • Place of Presentation: 東京
  • Invited
• [Presentation] Y. Redox control of cell death (2012)
  • Author(s): Ichijo, H., Sekine
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] ASK Family Kinases in Stress Response and Disease (2012)
  • Author(s): Ichijo, H
  • Organizer: The 4th Takeda Science Foundation Symposium on PharmaSciences "On the Frontiers of Chemical Biology"
  • Place of Presentation: 東京
• [Presentation] SOD1 as a molecular switch to initiate the homeostatic ER stress response (2012)
  • Author(s): Ichijo, H.
  • Organizer: The 2nd International Symposium by JSPS Core-to-Core Program "Cooperative International Framework in TGF-β Family Signaling"
  • Place of Presentation: 東京
• [Presentation] SOD1 as a molecular switch to initiate homeostatic ER stress response under conditions of zinc deficiency (2012)
  • Author(s): Ichijo, H.
  • Organizer: 第33回内藤コ ンファレンス
  • Place of Presentation: 札幌
• [Presentation] 亜鉛枯渇時に働く小胞体ストレス誘導スイッチとしてのSOD1の新規機能 (2012)
  • Author(s): 一條秀憲、本間謙吾
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] SOD1 as a molecular switch to initiate the homeostatic ER stress response under conditions of zinc deficiency (2012)
  • Author(s): Homma, K., Yamaguchi, N., Fujisawa, T., Nishitoh, H., Ichijo, H.
  • Organizer: The International Society for Zinc Biology (ISZB) 2012 Conference
  • Place of Presentation: Novotel, St.Kilda Australia.
• [Presentation] 細胞がストレスを感じるシグナル伝達の仕組みと疾患 (2012)
  • Author(s): 一條秀憲
  • Organizer: 日本分子生物学会第12回春季シンポジウム
  • Place of Presentation: 石和温泉 慶山
  • Invited
• [Presentation] SOD1 as a molecular switch to evoke ER stress in ALS and Zinc deficiency (2012)
  • Author(s): Hidenori Ichijo
  • Organizer: Program for Young Researcher Symposium in Europe' supported by Graduate School of Pharmaceutical Sciences, U-Tokyo Joint International Symposium
  • Place of Presentation: ケンブリッジ大学、イギリス
  • Invited
• [Presentation] Stress signaling in human diseases (2012)
  • Author(s): Hidenori Ichijo
  • Organizer: Program for Young Researcher Symposium in Europe' supported by Graduate School of Pharmaceutical Sciences, U-Tokyo Joint International Symposium
  • Place of Presentation: ボン大学、ドイツ
  • Invited
• [Presentation] ALS発症のメカニズム (2012)
  • Author(s): 一條秀憲
  • Organizer: 第５回東京アンチエイジングアカデミー
  • Place of Presentation: 大手町、東京
  • Invited
• [Presentation] SOD1 as a molecular switch to initiate homeostatic ER stress response under conditions of zinc deficiency (2012)
  • Author(s): Hidenori Ichijo
  • Organizer: 第33回内藤コンファレンス The 33rd Naito Conference: Oxygen Biology: Hypoxia, Oxidative Stress and Diseases
  • Place of Presentation: 札幌
  • Invited
• [Presentation] Stress signaling in cell death, inflammation and disease (2012)
  • Author(s): Hidenori Ichijo
  • Organizer: Fifty-third International Symposium on Biological Regulation and Enzyme Activity in Normal and Neoplastic Tissues
  • Place of Presentation: Bologna, Italy
  • Invited
• [Presentation] ストレス応答の破綻と神経変性疾患 (2012)
  • Author(s): 一條秀憲
  • Organizer: 第39回日本脳科学会
  • Place of Presentation: 小倉
  • Invited
• [Presentation] SOD1 as a molecular switch to initiate the homeostatic ER stress response (2012)
  • Author(s): Hidenori Ichijo
  • Organizer: The 2nd International Symposium by JSPS Core-to-Core Program “Cooperative International Framework in TGF-β Family Signaling” TGF-β Family: Signal Network and Tumor Microenvironment
  • Place of Presentation: 東京
  • Invited
• [Presentation] Redox control of cell death (2012)
  • Author(s): Hidenori Ichijo
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] SOD1 as a molecular switch to initiate the homeostatic ER stress response under conditions of zinc deficiency (2012)
  • Author(s): Homma, K., et al
  • Organizer: The International Society for Zinc Biology (ISZB) 2012 Conference(招待講演)
  • Place of Presentation: St.Kilda, Australia
• [Presentation] 亜鉛枯渇時に働く小胞体ストレス誘導スイッチとしてのSOD1の新規機能 (2012)
  • Author(s): 一條秀憲、本間謙吾
  • Organizer: 日本薬学会第132年会(招待講演)
  • Place of Presentation: 札幌
• [Presentation] Stress signaling in cell death, infiammation and disease (2011)
  • Author(s): Ichijo, H.
  • Organizer: The 23th Annual Meeting of the Korean Society for Molecular and Cellular Biology
  • Place of Presentation: Seoul, Korea.
• [Presentation] 亜鉛枯渇によるSOD1-Derlin-1結合を介した小胞体ストレスの生理的意義 (2011)
  • Author(s): 一條秀憲、本間謙吾、藤澤貴央、西頭英起
  • Organizer: 第22回日本微量元素学会学術集会
  • Place of Presentation: 京都
• [Presentation] 亜鉛枯渇によるSOD1-Derlin-1結合を介した小胞体ストレスの生理的意義 (2011)
  • Author(s): 一條秀憲 他
  • Organizer: 第22回日本微量元素学会学術集会(招待講演)
  • Place of Presentation: 京都
• [Presentation] Ichijo, H.Stress signaling in cell death, infiammation and disease (2011)
  • Author(s): Ichijo, H.
  • Organizer: The 23th Annual Meeting of the Korean Society for Molecular and Cellular Biology(招待講演)
  • Place of Presentation: Seoul, Korea
• [Presentation] ALS発症のメカニズム
  • Author(s): 一條秀憲
  • Organizer: 第5回東京アンチエイジングアカデミー
  • Place of Presentation: 東京