Hidenori ICHIJO

一條 秀憲 いちじょう ひでのり 1958年9月4日 徳島市生まれ(富田小学校、富田中学校、県立城東高校)
略歴
1985年 3月 東京医科歯科大学 歯学部 卒業
  1990年 3月 東京医科歯科大学 大学院歯学研究科博士課程修了 歯学博士
  1990年 4月 Ludwig癌研究所 Uppsala Branch留学
  1992年 4月 東京医科歯科大学・歯学部・口腔病理学講座・助手
  1995年 4月  (財)癌研究会・癌研究所・生化学部・研究員
  1998年 2月 東京医科歯科大学・大学院医歯学総合研究科・分子情報伝達学分野・教授
  2002年 9月 東京大学・大学院薬学系研究科・細胞情報学教室・教授
  2011年 4月  同  ・総長補佐(~2012年3月) 
  2012年 4月  同  ・大学院薬学系研究科・副研究科長(~2014年3月) 
  2012年10月  同  ・創薬オープンイノベーションセンター長(兼任〜2015年3月)
  2013年10月  同  ・大学院薬学系研究科・ワンストップ創薬共用センター長(兼任〜2017年3月)
  2015年 4月  同  ・創薬機構・機構長(兼任)
  2015年 4月  同  ・教育研究評議員(兼任〜2017年3月)
    現在に至る
学会役員等
  日本生化学会(副会長2007~2008・2011~2013・2015~2017/常務理事2013~2015)
  日本分子生物学会(理事2013~2016、第39回(2016年)大会長)、日本癌学会(評議員), 日本薬理学会(学術評議員)、
  日本薬学会(関東支部幹事)、口腔病学会(評議員)、日本口腔科学会(評議員)、  日本がん分子標的治療学会(評議員)、
  臨床ストレス応答学会(評議員/幹事)、日本学術会議(連携会員)、
  European research institute for integrated cellular pathology (ERI-ICP) (International Founding Member)、
  AAAS (American Association for the Advancement of Science)(member)
受賞歴  
  平成 9(1997)年度 歯科基礎医学会賞  
  平成10(1998)年度 日本癌学会奨励賞  
  平成13(2001)年度 日本歯科基礎医学会 ライオン学術賞  
  平成20(2008)年度 日本癌学会 JCA-Mauvernay Award  
  平成25(2013)年度 持田記念学術賞  
  平成27(2015)年度 高峰記念第一三共賞  
  平成28(2016)年度 上原賞  
CURRICULUM VITAE
Family name:
Forenames:
Ichijo
Hidenori
Date and place of birth: 4 September, 1958, Tokushima, Japan
Nationality: Japanese
Affiliation:  
  Position and title: Professor
  Dept./ Laboratory: Graduate School of Pharmaceutical Sciences/ Laboratory of Cell Signaling
  Institution: The University of Tokyo
  Address: 7-3-1 Hongo, Bunkyo-ku, Tokyo
  Phone: +81-3-5841-4859
  Fax: +81-3-5841-4798
  E-mail: ichijo (at) mol.f.u-tokyo.ac.jp

Education:
  Tokyo Medical and Dental University, April 1979- March 1985
D.D.S. Degree: Tokyo Medical and Dental University, 1985
  Resident of Oral Surgery, the University Hospital, Tokyo Medical and Dental University,
April 1985- March 1986
  Graduate student, First Department of Oral Surgery, Tokyo Medical and Dental University,
April 1986- March1990
Ph.D. Degree: Tokyo Medical and Dental University, 1990
Professional Experience / Research Experience:
  Postdoctoral fellow, The Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden,
April 1990-March 1993
  Research assistant, Department of Oral Pathology, Tokyo Medical and Dental University,
April 1992-March 1995   
  Associate, Department of Biochemistry, The Cancer Institute, Tokyo,
April 1995-April 1997
  Associate member, Department of Biochemistry, The Cancer Institute, Tokyo,
May 1997-Jan 1998
  Professor, Department of Biomaterials Science, Faculty of Dentistry, Tokyo Medical and Dental University, Feb 1998-Mar 2000
  Professor, Laboratory of Cell Signaling, Graduate School, Tokyo Medical and Dental University,
April 2000- Mar 2003
  Professor, Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Sept 2002-present
Recent Research Interests:
  Signal transduction of the MAP kinases, Apoptosis, Stress response
Editorial Membership
  Editorial Board:    2001-present Cell Death and Differentiation  
  Editorial Board:
Editor:
2005-2006
2007-2012
Journal of Oral Biosciences

  Plannning committee:
Advisory Board:
Associate Editor:
2005.1-2008.12
2008.1-present
2012.1-present
SEIKAGAKU
The Journal of Biochemistry

  Editorial Board: 2007.4-present The Japanese Dental Science Review
  Associate Editor: 2008.1-present Cancer Science
  Advisory Board: 2002-2007 Signal Transduction
  Editorial Board: 2003.5-present Journal of The Japanese Stomatological Society
  Editorial Board: 2004-present Oral Science International
  Editor 2011.10-present BBA General Subjects
  Editorial Advisory Board: 2013.4-present Molecular Pharmacology
  Advisory Editorial Board: 2015-present Oncotarget “Autophagy and Cell Death”
  Editorial Board: 2015-present J. Biol. Chem.
Membership (Scientific Society)
  Vice President:

Standing Director:
Councilor:
2007-2008, 2011-2013, 2015-2017
20013-2015
2006-present
The Japanese Biochemical Society (Member:1995-)
  Executive member:
The 39th Chairman
2013-present
2016.11/30-12/2
The Molecular Biology Society of Japan (Member:1997-)
  Councilor: 2002-present Japanese Cancer Association (Member:1989-)
  A member of Scientific Council: 2004-present The Japanese Pharmacological Society (Member:2003-)
  Officer of Kanto Branch 2017-present The Pharmaceutical Society of Japan (Member:2002-)
  Councilor 2003-present The Stomatological Society, Japan (Member:1985-)
  Councilor:
Executive member:
2006-present
2009-present
Japanese Stomatological Society (Member: 2003-)
  Councilor: 2009-present The Japanese Association for Molecular Target Therapy of Cancer
(Member: 2009-)
  Councilor: 2005-present The Biomedical Society for Stress Response (Member: 2005-)
  Committee Member: 2011-present Science Council of Japan
  International Founding Member 2010-present European research institute for integrated cellular pathology
(ERI-ICP)
  Member: 1998-present AAAS (American Association for the Advancement of Science)
  Councilor: 2000-present Japanese association for oral biology (Member: 1993-) 
  Councilor: 2010-present The Japanese Soceity for Cell Death Research
  Member: 2004-present The Japanese Society of Toxicology
  Member: 1986-2002 Japanese Society of Bone and Mineral Research
  Member: 1998-2001 Japanese Society for Immunology  
  Member: 1985-1996 Japanese Society of Oral and Maxillofacial Surgeons
Awards:
  Academic award for the Japanese Association for Oral Biology, 1997
Incitement Award of the Japanese Cancer Association, 1998
LION Award for the Japanese Association for Oral Biology, 2001
JCA-Mauvernay Award of the Japanese Cancer Association, 2008
Academic Award of the Mochida Memorial foundation, 2013
Takamine Memorial Daiichi Sankyo Prize, 2015
Uehara Prize, 2016
 
(As of June, 2017)

 

Selected Papers  

  1. Hattori, K., Naguro, I., Okabe, K., Funatsu, T., Furutani, S., Takeda, K. and Ichijo, H.
    ASK1 signaling regulates brown and beige adipocyte function.
    Nat. Commun., 7: 11158 (2016).

  2. Sekine, S., Yao, A., Hattori, K., Sugawara, S., Naguro, I., Koike, M., Uchiyama, Y., Takeda, K. and Ichijo, H.
    The ablation of mitochondrial protein phosphatase Pgam5 confers resistance against metabolic stress.
    EBioMedicine, 5: 82-92 (2016).

  3. Fujisawa, T., Takahashi, M., Tsukamoto, Y., Yamaguchi, N., Nakoji, M., Endo, M., Kodaira, H., Hayashi, Y., Nishitoh, H., Naguro, I., Homma, K. and Ichijo, H.
    The ASK1-specific inhibitors K811 and K812 prolong survival in a mouse model of amyotrophic lateral sclerosis.
    Hum. Mol. Genet., 25, 245-253 (2016).

  4. Kadowaki, H., Nagai, A., Maruyama, T., Takami, Y., Fitrah, P.S., Kato, H., Honda, A., Hatta, T., Natsume, T., Sato, T., Kai, H., Ichijo, H. and Nishitoh, H.
    Preemptive quality control protects the ER from protein overload via the proximity of ERAD components and SRP.
    Cell Rep., 113, 944-956 (2015).

  5. Miyakawa, K., Matsunaga, S., Kanou, K., Matsuzawa, A., Morishita, R., Kudoh, A., Shindo, K., Yokoyama, M., Sato, H., Kimura, H., Tamura, T., Yamamoto, N., Ichijo, H., Takaori-Kondo, A. and Ryo, A.
    ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction.
    Nat. Commun., 6, 6945 (2015).

  6. Okazaki, T., Higuchi, M., Takeda, K., Iwatsuki-Horimoto, K., Kiso, M., Miyagishi, M., Yanai, H., Kato, A., Yoneyama, M., Fujita, T., Taniguchi, T., Kawaoka, Y., Ichijo, H. and Gotoh, Y.
    The ASK family kinases differentially mediate induction of type I interferon and apoptosis during the antiviral response.
    Sci. Signal., 8, ra78 (2015).

  7. Mosallanejad, K., Sekine, Y., Ishikura-Kinoshita, S., Kumagai, K., Nagano, T., Matsuzawa, A.,Takeda, K., Naguro, I. and Ichijo, H.
    The DEAH-Box RNA Helicase DHX15 activates NF-κB and MAPK signaling downstream of MAVS during antiviral responses.
    Sci. Signal., 7, ra40 (2014).

  8. Maruyama, T., Araki, T., Kawarazaki, Y., Naguro, I., Heynen, S., Aza-Blanc, P., Ronai, Z., Matsuzawa, A., Ichijo, H. 
    Roquin-2 promotes ubiquitin-mediated degradation of ASK1 to regulate stress responses.
    Sci. Signal., 7, ra8 (2014).

  9. Homma, K., Fujisawa, T., Tsuburaya, N., Yamaguchi, N., Kadowaki, H., Takeda, K., Nishitoh, H.,  Matsuzawa, A., Naguro, I., and Ichijo, H.
    SOD1 as a molecular switch for initiating the homeostatic ER stress response under zinc deficiency.
    Mol. Cell, 52, 75-86 (2013).


  10. Naguro, I., Umeda, T., Kobayashi, Y., Maruyama, J., Hattori, K., Shimizu, Y., Kataoka, K., Kim-Mitsuyama, S., Uchida, S., Vandewalle, A., Noguchi, T., Nishitoh, H., Matsuzawa, A., Takeda, K. and Ichijo, H.
    ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney.
    Nat. Commun., 2012;3:1285 (2012).

  11. Sekine, Y., Hatanaka, R., Watanabe, T., Sono, N., Iemura, S., Natsume, T., Kuranaga, E., Miura, M., Takeda, K. and Ichijo, H.
    The kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5.
    Mol. Cell, 48, 692-704 (2012).

  12. Sekine,S., Kanamaru, Y., Koike, M., Nishihara, A., Okada, M., Kinoshita, H., Kamiyama, M., Maruyama, J., Uchiyama, Y., Ishihara, N., Takeda, K. and Ichijo, H.
    Rhomboid protease PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM5.
    J. Biol. Chem., 287, 34635-34645 (2012).

  13. Fujisawa, T., Homma, K., Yamaguchi, N., Kadowaki, H., Tsuburaya, N., Naguro, I., Matsuzawa, A., Takeda, K., Takahashi, Y., Goto, J., Tsuji, S., Nishitoh, H. and Ichijo, H.
    A novel monoclonal antibody reveals a conformational alteration shared by amyotrophic lateral sclerosis-linked SOD1 mutants.
    Ann. Neurol., 72, 739-749 (2012).

  14. Hayakawa, Y., Hirata, Y., Nakagawa, H., Sakamoto, K., Hikiba, Y., Kinoshita, H., Nakata, W., Takahashi, R., Tateishi, K., Tada, M., Akanuma, M., Yoshida, H., Takeda, K., Ichijo, H., Omata, M., Maeda, S., Koike, K.
    Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer.
    Proc. Natl. Acad. Sci. USA., 108, 780-785 (2011).

  15. 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.
    p38 MAP kinase regulates the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors.
    J. Cell Sci., 124, 3006-3016 (2011).

  16. Hayakawa, T., Kato, K., Hayakawa, R., Hisamoto, N., Matsumoto, K., Takeda, K. and Ichijo, H.
    Regulation of anoxic death in Caenorhabditis elegans by mammalian apoptosis signal-regulating kinase (ASK) family proteins
    Genetics, 187, 785-792 (2011).

  17. Maruyama, T., Kadowaki, H., Okamoto, N., Nagai, A., Naguro, I., Matsuzawa, A., Shibuya, H., Tanaka, K., Murata, S., Takeda, K., Nishitoh, H. and Ichijo, H. CHIP-dependent termination of MEKK2 regulates temporal ERK activation required for proper hyperosmotic response.
    EMBO J., 29, 2501-2514 (2010).

  18. Seong, H.A., Jung, H., Ichijo, H. and Ha, H.
    Reciprocal negative regulation of PDK1 and ASK1 signaling by direct interaction and phosphorylation.
    J. Biol. Chem., 285, 2397-2414 (2010)

  19. Nagai, H,, Noguchi, T., Homma, K., Katagiri, K., Takeda, K., Matsuzawa, A. and Ichijo, H.
    Ubiquitin-like sequence in ASK1 plays critical roles in the recognition and stabilization by USP9X and oxidative stress-induced cell death.
    Mol. Cell, 36, 805-818 (2009).

  20. Cekic, C., Casella, C.R., Eaves, C.A., Matsuzawa, A., Ichijo, H. and Mitchell, T.C.
    Selective activation of the p38 MAPK pathway by synthetic monophosphoryl lipid A.
    J. Biol. Chem., 284, 31982-31991 (2009).

  21. Takeda, K., Komuro, Y., Hayakawa, T., Oguchi, H., Ishida, Y., Murakami, S., Noguchi, T., Kinoshita, H., Sekine, Y., Iemura, S., Natsume, T., and Ichijo, H.
    Mitochondrial Phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1.
    Proc. Natl. Acad. Sci. USA., 106, 12301-12305 (2009).

  22. Kundu, M., Pathak, S.K., Kumawat, K., Basu, S., Chatterjee, G., Pathak, S., Noguchi, T., Takeda, K., Ichijo, H., Thien, C.B., Langdon, W.Y. and Basu, J.
    A TNF- and c-Cbl-dependent FLIP(S)-degradation pathway and its function in Mycobacterium tuberculosis-induced macrophage apoptosis.
    Nat. Immunol., 10, 918-926 (2009).

  23. Zhou, J., Shao, Z., Kerkela, R., Ichijo, H., Muslin, A., Pombo, C. and Force, T.
    Serine 58 of 14-3-3{zeta} is a molecular switch regulating ASK1 and oxidant stress-induced cell death.
    Mol Cell Biol., 29, 4167-4176 (2009).

  24. Waak, J., Weber, S. S., Gorner, K., Schall, C., Ichijo, H., Stehle, T. and Kahle, P. J.
    Oxidizable residues mediating protein stability and cytoprotective interaction of DJ-1 with apoptosis signal-regulating kinase 1.
    J. Biol. Chem., 284, 14245-14257 (2009).

  25. Iriyama, T., Takeda, K., Nakamura, H., Morimoto, Y., Kuroiwa, T., Mizukami, J., Umeda, T., Noguchi, T., Naguro, I., Nishitoh, H., Saegusa, K., Tobiume, K., Homma, T., Shimada, Y., Tsuda, H., Aiko, S., Imoto, I., Inazawa, J., Chida, K., Kamei, Y., Kozuma, S., Taketani, Y., Matsuzawa, A. and Ichijo, H.
    ASK1 and ASK2 differentially regulate the counteracting roles of apoptosis and inflammation in tumorigenesis.
    EMBO J., 28, 843-853 (2009).

  26. Nishitoh, H., Kadowaki, H., Nagai, A., Maruyama, T., Yokota, T., Fukutomi, H., Noguchi, T., Matsuzawa, A., Takeda, K. and Ichijo, H.
    ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1.
    Genes. Dev., 22, 1451-1464 (2008).

  27. Noguchi, T., Ishii, K., Fukutomi, H., Naguro, I., Matsuzawa, A., Takeda, K. and Ichijo, H.
    Requirement of reactive oxygen species-dependent activation of ASK1-p38 MAP kinase pathway for extracelluler ATP-induced apoptosis in macrophage.
    J. Biol. Chem., 283, 7657-7665 (2008).

  28. Fujino, G., Noguchi, T., Matsuzawa, A., Yamauchi, S., Saitoh, M., Takeda, K. and Ichijo, H.
    Thioredoxin and TRAF family proteins regulate ROS-dependent activation of ASK1 through reciprocal modulation of the N-terminal homophilic interaction of ASK1.
    Mol. Cell. Biol., 27, 8152-8163 (2007).

  29. Osaka, N., Takahashi, T., Murakami, S., Matsuzawa, A., Noguchi, T., Fujiwara, T., Aburatani, H., Moriyama, K., Takeda, K. and Ichijo, H.
    ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds.
    J. Cell Biol., 176, 903-909 (2007).

  30. Takeda, K., Shimozono, R., Noguchi, T., Umeda, T., Morimoto, Y., Naguro, I., Tobiume, K., Saitoh, M., Matsuzawa, A. and Ichijo, H.
    Apoptosis signal-regulating kinase 2 (ASK2) functions as a MAP3K in a heteromeric complex with ASK1.
    J. Biol. Chem., 282, 7522-7531 (2007).

  31. Kitagawa, D., Kajiho, H., Negishi, T., Ura, S., Watanabe, T., Wada, T., Ichijo, H., Katada, T. and Nishina, H.
    Release of RASSF1C from the nucleus by Daxx degradation links DNA damage and SAPK/JNK activation.
    EMBO J., 25, 3286-3297 (2006).

  32. Chiang, E., Dang, O., Anderson, K., Matsuzawa, A., Ichijo, H. and David, M.
    Apoptosis- regulating signal kinase 1 is required for reactive oxygen species-mediated activation of IFN regulatory factor 3 by lipopolysaccharide.
    J. Immunol., 176, 5720-5724 (2006).

  33. Liu, Q., Wilkins, B.J., Lee, Y.J., Ichijo, H. and Molkentin, J.D.
    Direct Interaction and Reciprocal Regulation Between ASK1 and Calcineurin-NFAT Controls Cardiomyocyte Death and Growth.
    Mol. Cell. Biol., 26, 3785-3797 (2006).

  34. Noguchi, T., Takeda, K., Matsuzawa, A., Saegusa, K., Nakano, H., Gohda, J., Inoue, J. and Ichijo, H.
    Recruitment of TRAF family proteins to the ASK1 signalosome is essential for oxidative stress-induced cell death.
    J. Biol. Chem., 280, 37033-37040 (2005).

  35. Matsuzawa, A., Saegusa, K., Noguchi, T., Sadamitsu, C., Nishitoh, H., Nagai, S., Koyasu, S., Matsumoto, K., Takeda, K. and Ichijo, H.
    ROS-dependent activation of TRAF6-ASK1-p38 pathway is selectively required for TLR-4 mediated innate immunity.
    Nat. Immunol., 6, 587-592 (2005).

  36. Junn, E., Taniguchi, H., Jeong, B.S., Zhao, X., Ichijo, H. and Mouradian, M.,M.
    Interaction of DJ-1 with Daxx inhibits ASK1 activity and cell death.
    Proc. Natl. Acad. Sci. USA., 102, 9691-9696 (2005).

  37. Kaneto, H., Nakatani, Y., Miyatsuka, T., Kawamori, D., Matsuoka, T.A., Matsuhisa, M., Kajimoto, Y., Ichijo, H., Yamasaki, Y. and Hori, M.
    Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide.
    Nat. Med., 10, 1128-1132 (2004).

  38. Takeda, K., Matsuzawa, A., Nishitoh, H., Tobiume, K., Kishida, S., Ninomiya,T., Tsuji, J., Matsumoto, K., and Ichijo, H.
    Involvement of ASK1 in Ca2+-induced p38 MAP kinase activation.
    EMBO Rep., 5, 161-166 (2004).

  39. Yamaguchi, O., Watanabe, T., Nishida, K., Kashiwase, K., Higuchi, Y., Takeda, T., Hikoso, S., Hirotani, S., Asahi, M., Taniike, M., Nakai, A., Tsujimoto, I., Matsumura, Y., Miyazaki, J., Chien, K.R., Matsuzawa, A., Sadamitsu, C., Ichijo, H., Baccarini, M., Hori1, M. and Otsu, K.
    Cardiac-specific Disruption of c-raf-1 Gene Induces Cardiac Dysfunction and Apoptosis.
    J. Clin. Invest., 114, 937-943 (2004).

  40. Huang, S., Shu, L., Easton, J., Harwood, F. C., Germain, G. S., Ichijo, H. and Houghton, P. J.
    Inhibition of Mammalian Target of Rapamycin Activates Apoptosis Signal-Regulating Kinase 1 Signaling by Suppressing Protein Phosphatase 5 Activity.
    J. Biol. Chem., 279, 36490-36496 (2004).

  41. Song, S., Kim, S.Y., Hong, Y.M., Jo, D.G., Lee, J.Y., Shim, S.M., Chung, C.W., Seo, S.J., Yoo, Y.J., Koh, J.Y., Lee, M.C., Yates, A.J., Ichijo, H., Jung, Y.K.
    Essential role of E2-25K/Hip-2 in mediating amyloid-beta neurotoxicity.
    Mol. Cell, 12, 553-563 (2003).

  42. Cho, S.-G., Kim, J.W., Lee, Y.H., Hwang, H.S., Kim, M.-S., Ryoo, K., Kim, M.J., Noh K.T., Kim, E.K. Cho, J.-H., Yoon, K.W., Cho, E.-G., Park, H.-S., Chi, S.W., Lee, M.-J., Kang, S.S., Ichijo, H. and Choi, E.-J.
    Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities.
    J. Cell Biol., 163, 71-81 (2003).

  43. Yamaguchi, O., Higuchi, Y., Hirotani, S., Kashiwase, K., Nakayama, H., Hikoso, S., Takeda, T., Watanabe, T., Asahi, M., Taniike, M., Matsumura, Y., Tsujimoto, I., Hongo, K., Kusakari, Y., Kurihara, S., Nishida, K., Ichijo, H., Hori, M. and Otsu, K.
    Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling.
    Proc. Natl. Acad. Sci. USA., 100, 15883-15888 (2003).

  44. Matsukawa, J., Nakayama, K., Nagao, T., Ichijo, H. and Urushidani, T.
    Role of ADP-ribosylation factor 6 (ARF6) in gastric acid secretion.
    J. Biol. Chem., 278, 36470-36475 (2003).

  45. Huang, H., Shj, L., Dilling, M.B, Easton, J., Harwood, F.C., Ichijo, H. and Houghton, P.J.
    Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/ p21Cip1.
    Mol. Cell, 11, 1491-1501 (2003).

  46. Galvan, V., Logvinova, A., Sperandio, S., Ichijo, H. and Bredesen, D.E.
    Type 1 insulin-like growth factor receptor (IGF-IR) signaling inhibits apoptosis signal-regulating kinase 1 (ASK1).
    J. Biol. Chem., 278, 13325-13332 (2003).

  47. Gilot, D., Loyer, P., Corlu, A., Glaise, D., Lagadic-Gossmann, D., Atfi, A., Morel, F., Ichijo, H. and Guguen-Guillouzo, C.
    Liver protection from apoptosis requires both blockage of initiator caspase activities and inhibition of ASK1/JNK pathway via glutathione S-transferase regulation.
    J. Biol. Chem., 277, 49220-49229 (2002).

  48. Matsuura, H., Nishitoh, H., Takeda, K., Matsuzawa, A., Amagasa, T., Ito, M., Yoshioka, K. and Ichijo, H.
    Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway: a new mode of regulation of the MAP kinase cascade.
    J. Biol. Chem., 277, 40703-40709 (2002).

  49. Inoshita, S., Takeda, K., Hatai, T., Terada, Y., Sano, M., Hata, J., Umezawa, A. and Ichijo, H.
    Phosphorylation and Inactivation of Mcl-1 by c-Jun N-terminal Kinase (JNK) in response to oxidative stress.
    J. Biol. Chem., 277, 43730-43734 (2002).

  50. Kuranaga, E., Kanuka, H., Igaki, T., Sawamoto, K., Ichijo, H., Okano, H. and Miura, M.
    Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila.
    Nat. Cell Biol., 4, 705-710 (2002).

  51. Nishitoh, H., Matsuzawa, A., Tobiume, K., Saegusa, K., Takeda, K., Inoue, K., Hori, S., Kakizuka, A. and Ichijo, H.
    ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats.
    Genes Dev., 16, 1345-1355 (2002).

  52. Morita, K., Saitoh, M., Tobiume, K., Matsuura, H., Enomoto, S., Nishitoh, H. and Ichijo, H.
    Negative feedback regulation of ASK1 by protein phophatase 5 (PP5) in response to oxidative stress.
    EMBO J., 20, 6028-6036 (2001).

  53. Zou, X., Tsutsui, T., Ray, D., Blomquist, J.F., Ichijo, H., Ucker, D.S. and Kiyokawa, H.
    The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1 (ASK1).
    Mol. Cell. Biol., 21, 4818-4828 (2001).

  54. Geleziunas, R., Xu, W., Takeda, K., Ichijo, H. and Greene W.C.
    HIV-1 nef inhibits ASK1-dependent death signalingproviding a potential mechanism for protecting the infected host cell.
    Nature, 410, 834-838 (2001).

  55. Cho, S.-G., Lee, Y., Park, H.-S., Ryoo, K., Kang, K., Park, J., Eom, S.-J., Kim, M., Chang, T.-S., Choi, S.-Y., Shim, J., Kim, Y., Dong, M.-S., Lee, M.-J., Kim, S., Ichijo, H. and Choi, E.-J.
    Glutathione s-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1 (ASK1).
    J. Biol. Chem., 276, 12749-12755 (2001).

  56. Tobiume, K., Matsuzawa, A., Takahashi, T., Nishitoh, H., Morita, K., Takeda, K., Minowa, O., Miyazono, K., Noda, T. and Ichijo, H.
    ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis.
    EMBO reports, 2, 222-228 (2001).

  57. Sayama, K., Hanakawa, Y., Shirakata, Y., Yamasaki, K., Sawada, Y., Sun, L., Yamanishi, K., Ichijo, H. and Hashimoto, K.
    Apoptosis signal regulating kinase 1 (ASK1) is an intracellular inducer of keratinocyte differentiation.
    J. Biol. Chem., 276, 999-1004 (2001).

  58. Sawada, Y., Nakamura, K., Doi, K., Takeda, K., Tobiume, K., Saitoh, M., Morita, K., Komuro, I., Kurt De Vos, Sheetz, M. and Ichijo, H.
    Rap1 is Involved in Cell Stretching Modulation of p38 but not ERK or JNK MAP Kinase.
    J. Cell Sci., 114, 1221-1227 (2001).

  59. Takeda, K., Hatai, T., Hamazaki, S., Nishitoh, H., Saitoh, M. and Ichijo H.
    Apoptosis Signal- regulating Kinase 1 (ASK1) Induces Neuronal Differentiation and Survival of PC12 Cells.
    J. Biol. Chem., 275, 9805-9813 (2000).

  60. Liu, H., Nishitoh, H., Ichijo, H. and Kyriakis, J.M.
    Activation of apoptosis signal-regulating kinase 1 (ASK1) by tumor necrosis factor receptor- associated factor 2 (TRAF2) requires prior dissociation of the ASK1 inhibitor Thioredoxin.
    Mol. Cell. Biol., 20, 2198-2208 (2000).

  61. Kanamoto, T., Mota, M., Takeda, K., Rubin, L.L., Miyazono, K., Ichijo, H. and Bazenet, C.E.
    Role of apoptosis signal-regulating kinase in regulation of the c-Jun N-terminal Kinase pathway and apoptosis in sympathetic neurons.
    Mol. Cell. Biol., 20, 196-204 (2000).

  62. Hatai, T., Matsuzawa, A., Inoshita, S., Mochida, Y., Kuroda, T., Sakamaki, K., Kuida, K., Yonehara, S., Ichijo, H. and Takeda, K.
    Execution of ASK1-induced Apoptosis by the Mitochondria-dependent Caspase Activation.
    J. Biol. Chem., 275, 26576-26581 (2000).

  63. Mochida, Y., Takeda, K., Saitoh, M., Nishitoh, H., Amagasa, T., Ninomiya-Tsuji, j., Matsumoto, K. and Ichijo, H.
    ASK1 inhibits IL-1-induced NF-kB activity through disruption of TRAF6-TAK1 interaction.
    J. Biol. Chem., 275, 32747-32752 (2000)
    .

  64. Yamamoto, K., Ichijo, H. and Korsmeyer, S.J.
    BCL-2 is phosphorylated and inactivated by an ASK1/JNK pathway normally activated at G2/M.
    Mol. Cell Biol., 19, 8469-8478 (1999).

  65. Wang,T.H., Popp,D.M., Wang,H.S., Saitoh, M., Mural, J.G., Henley, D.C., Ichijo, H. and Wimalasena,J.
    Microtubule dysfunction induced by paclitaxel initiates apoptosis through both c-jun N-terminal kinase (JNK)-dependent and -independent pathways in ovarian cancer cells.
    J. Biol. Chem., 274, 8208-8216 (1999).

  66. Asada, M., Yamada, T., Ichijo, H., Delia, D., Miyazono, K., Fukumuro, K. and Mizutani, S.
    Apoptosis inhibitory activity of cytoplasmic p21Cip1/WAF1 in monocytic differentiation.
    EMBO J., 18, 1223-1234 (1999).

  67. Fujii, M., Takeda, K., Imamura, T., Aoki, H., Sampath, T.K., Enomoto, S., Kawabata M., Kato, M., Ichijo, H. and Miyazono, K.
    Roles of bone morphogenetic protein type I receptors and smad proteins in osteoblast and chondroblast differentiation.
    Mol. Biol. Cell, 10, 3801-3813 (1999).

  68. Nishitoh, H., Saitoh, M., Mochida, Y., Takeda, K., Nakano, H., Rothe, M., Miyazono, K. and Ichijo, H.
    ASK1 is essential for JNK/SAPK activation by TRAF2.
    Mol. Cell, 2, 389-395 (1998).

  69. Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono K. and Ichijo, H.
    Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1.
    EMBO J., 17, 2596-2606 (1998).

  70. Chang, HY., Nishitoh, H., Yang, X., Ichijo, H. and Baltimore, D.
    Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein daxx.
    Science, 281, 1860-1863 (1998).

  71. Berestetskaya, Y.V., Faure, M.P., Ichijo, H., Tatyana, A. and Yasenetskaya, V.
    Regulation of apoptosis by alhpa subunits of G12 and G13 proteins via apoptosis signal-regulating.
    J. Biol. Chem., 273, 27816-27823 (1998).

  72. Takeda, K., Ichijo, H., Fujii, M., Mochida, Y., Saitoh, M., Nishitoh, H., Sampath, T.K. and Miyazono, K.
    Identification of a novel bone morphogenetic protein-responsive gene that may function as a noncoding RNA.
    J. Biol. Chem., 273, 17079-17085 (1998).

  73. Wang, T.-H., Wang, H.-S., Ichijo, H., Giannakakou, P., Foster, J.S., Fojo, T. and Wimalasena, J.
    Microtuble-interfering agents activate c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) through both ras and apoptosis signal-regulating kinase (ASK1) pathways.
    J. Biol. Chem., 273, 4928-4936 (1998).

  74. Ichijo, H. Nishida, E., Irie, K., ten Dijke, P., Saitoh, M., Moriguchi, T., Takagi, M., Matsumoto, K., Miyazono, K. and Gotoh, Y.
    Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways.
    Science, 275, 90-94 (1997).

  75. Saitoh, M., Nishitoh, H., Amagasa, T., Miyazono, K., Takagi, M. and Ichijo, H.
    Identification of important regions in the cytoplasmic juxtamembrane domain of type I receptor that separate signaling pathways of transforming growth factor-β.
    J. Biol. Chem., 271, 2769-2775 (1996).

  76. Nishitoh, H., Ichijo, H., Kimura, M., Matsumoto, T., Makishima, F., Yamaguchi, A., Yamashita, H., Enomoto, S. and Miyazono, K.
    Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5.
    J. Biol. Chem., 271, 21345-21352 (1996).

  77. Okadome, T., Oeda, E., Saitoh, M., Ichijo, H., Moses, H.L. Miyazono, K. and Kawabata, M.
    Characterization of the interaction of FKBP12 with the transforming growth factor-β type I receptor in vivo.
    J. Biol. Chem., 271, 21687-21690 (1996).

  78. ten Dijke, P., Yamashita, H., Sampath, K., Reddi, H., Riddle, D., Ichijo, H., Heldin, C.-H., Miyazono, K.
    Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4.
    J. Biol. Chem., 269, 16985-16988  (1994).

  79. ten Dijke, P., Yamashita, H., Ichijo, H., Franzen, P., Laiho, M., Miyazono, K. and Heldin, C.-H. 
    Characterization of type I receptors for transforming growth factor-β and activin.
    Science, 264, 101-104 (1994).

  80. Yamashita, H., Ichijo, H., Grimsby, S., Moren, A., ten Dijke, P. and Miyazono, K.
    Endoglin forms a heteromeric complex with the signalling receptors for transforming growth factor-β.
    J. Biol. Chem., 269, 1995-2001 (1994).

  81. Franzen, P., ten Dijke, P., Ichijo, H., Yamashita, H., Schulz, P., Heldin, C.-H. and Miyazono, K.
    Cloning of a TGF-β type I receptor that forms a heteromeric complex with the TGF-β type II receptor.
    Cell, 75, 681-692 (1993).

  82. Ichijo, H., Hellman, U., Wernstedt, C., Gonez, L.-J., Claesson-Welsh, L., Heldin, C.-H. and Miyazono, K.
    Molecular cloning and characterization of ficolin, a multimeric protein with fibrinogen- and collagen-like domains.
    J. Biol. Chem., 268, 14505-14513 (1993).

  83. Ichijo, H., Ronnstrand, L., Miyagawa, K., Ohashi, H., Heldin, C.-H. and Miyazono, K.
    Purification of transforming growth factor-β1 binding proteins from porcine uterus membranes.
    J. Biol. Chem., 266, 22459-22464 (1991).

  84. Ichijo, H., Momose, F., and Miyazono, K.
    Biological effects and binding properties of transforming growth factor-β on human oral squamous cell carcinoma cells.
    Exp. Cell Res., 187, 263-269 (1990).