Studies on signaling pathways mediated by Nucling, a novel apoptosis-associating protein, in the development of inflammatory disorders and tumors

• Project/Area Number: 22590286
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokushima
• Principal Investigator: SAKAI Takashi 徳島大学, 疾患酵素学研究センター, 准教授 (80284321)
• Co-Investigator(Kenkyū-buntansha): FUKUI Kiyoshi 徳島大学, 疾患酵素学研究センター, 教授 (00175564)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ヌクリング / NF-κB / アポトーシス / 炎症性疾患 / 発ガン / Nucling / 肝炎・肝癌

Research Abstract

We revealed that Nucling is important for the strict regulationof NF-・B signal in resting state. Aberrant activation of NF-・B in Nucling-deficient tissues or cells showed defect of apoptosis pathways resulted in the resistance against cytotoxic stress. It is possibly one of the factors for the high prevalence ratios of hepatitis and hepatic cancer. These results will lead to the elucidation of the regulatory mechanism of the pathogenesis of the diseases or to the development of novel therapeutic strategies.

Research Products

• [Journal Article] Nucling, a novel protein associated with NF-・B, regulates endotoxin-induced apoptosis in vivo (2013)
  • Author(s): Sun Mi Kim, Sakai, T., Huy Van Dang, Nam Hoang Tran, Ono, K., Ishimura, K. and Fukui, K
  • Journal Title: J. Biochem Volume: Vol. 153、No. 1 Issue: 1 Pages: 93-101
  • DOI: 10.1093/jb/mvs119
  • Peer Reviewed
• [Journal Article] The role of kupffer cells in carbon tetrachloride intoxication in mice (2012)
  • Author(s): Kiso, K., Ueno, S., Fukuda, M., Ichi, I., Kobayashi, K., Sakai, T., Fukui, K., Kojo, S
  • Journal Title: Biol. Pharm. Bull Volume: Vol. 35、No. 6 Pages: 980-983
  • NAID: 130001872185
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22687543
  • Peer Reviewed
• [Journal Article] The Role of Kupffer Cells in Carbon Tetrachloride Intoxication in Mice (2012)
  • Author(s): Kaori Kiso
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 35 Issue: 6 Pages: 980-983
  • DOI: 10.1248/bpb.35.980
  • NAID: 130001872185
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] D-amino acid oxidase gene therapy sensitizes glioma cells to the antiglycolytic effect of 3-bromopyruvate (2012)
  • Author(s): Salah Mohamed El Sayed, et al
  • Journal Title: Cancer Gene Therapy Volume: 19 Issue: 1 Pages: 40-926
  • DOI: 10.1038/cgt.2011.59
  • Peer Reviewed
• [Journal Article] 3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects (2012)
  • Author(s): Salah Mohamed El Sayed, et al
  • Journal Title: Journal of Bioenergetics and Biomembranes Volume: 44 Issue: 1 Pages: 61-79
  • DOI: 10.1007/s10863-012-9409-4
  • Peer Reviewed
• [Journal Article] Inflammatory disease and cancer with a decrease in Kupffer cell numbers in Nucling-knockout mice (2010)
  • Author(s): Sakai, T., Liu, L., Teng, X. C., Ishimaru, N., Mukai-Sakai, R., Tran, N. H., Kim, S. M., Sano, N., Hayashi, Y., Kaji, R. and Fukui, K
  • Journal Title: Int. J. Cancer Volume: Vol. 126 Issue: 5 Pages: 1079-1094
  • DOI: 10.1002/ijc.24789
  • Peer Reviewed
• [Journal Article] NF-kappaB regulates the expression of Nucling, a novel apoptosis regulator, with involvement of proteasome and caspase for its degradation (2010)
  • Author(s): Tran N H, Sakai, T., Kim, S. M. and Fukui, K
  • Journal Title: J Biochem Volume: Vol. 148、No.5 Issue: 5 Pages: 573-580
  • DOI: 10.1093/jb/mvq089
  • Peer Reviewed
• [Journal Article] The Effect of Risperidone on D-Amino Acid Oxidase Activity as a Hypothesis for a Novel Mechanism of Action in the Treatment of Schizophrenia (2010)
  • Author(s): Rabab M., Abou El-Magd
  • Journal Title: Journal of Psychopharmacology Volume: 24 Pages: 1055-1067
  • Peer Reviewed
• [Journal Article] NF-kappaB regulates the expression of Nucling, a novel apoptosis regulator, with involvement of proteasome and caspase for its degradation (2010)
  • Author(s): Nam Hoang Tran
  • Journal Title: Journal of Biochemistry Volume: 148 Pages: 573-580
  • Peer Reviewed
• [Journal Article] Potential cytotoxic effect of hydroxypyruvate produced from D-serine by astroglial D-amino acid oxidase (2010)
  • Author(s): Seong Pit Chung
  • Journal Title: Journal of Biochemistry Volume: 148 Pages: 743-753
  • Peer Reviewed
• [Journal Article] Bioprocess development of the production of the mutant P-219-L human D-amino acid oxidase for high soluble fraction expression in recombinant Escherichia coli (2010)
  • Author(s): Rabab M., Abou El-Magd
  • Journal Title: Biochemical Engineering Journal Volume: 52 Pages: 236-247
  • Peer Reviewed
• [Journal Article] The role of Kupffer cells in carbon tetrachloride intoxieation in mice
  • Author(s): Kiso K, et al
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: (印刷中)
  • Peer Reviewed
• [Presentation] 新規NF-・B制御分子ヌクリングは非アルコール性脂肪肝及び糖尿病発症抑制に重要で或る (2012)
  • Author(s): 坂井隆志
  • Organizer: 第16回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京都港区
  • Year and Date: 2012-11-23
• [Presentation] ホモシステイン代謝系における新規NF-・B制御因子ヌクリングの関与 (2012)
  • Author(s): 佐古有季哉
  • Organizer: 日本ビタミン学会第64回大会
  • Place of Presentation: 岐阜市
  • Year and Date: 2012-06-23
• [Presentation] 新規NF-・B制御分子ヌクリングの炎症性病態への関与についての検討 (2012)
  • Author(s): 金善美
  • Organizer: 第53回日本生化学会 中国・四国支部例会
  • Place of Presentation: 岡山市
  • Year and Date: 2012-05-18
• [Presentation] ホモシステイン代謝系における新規NF-κB制御因子ヌクリングの関与 (2012)
  • Author(s): 佐古 有季哉
  • Organizer: 日本ビタミン学会第64回大会
  • Place of Presentation: 長良川国際会議場（岐阜県）
• [Presentation] 新規NF-κB制御分子ヌクリングは非アルコール性脂肪肝及び糖尿病発症抑制に重要である (2012)
  • Author(s): 坂井 隆志
  • Organizer: 第16回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京大学（東京都）
• [Presentation] 四塩化炭素中毒におけるKupffer細胞による肝炎拡大機構 (2012)
  • Author(s): 木曽 かおり
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡（福岡県）
• [Presentation] 新規NF-κB制御分子ヌクリングはLPS刺激により誘導される細胞死を制御している (2012)
  • Author(s): 金 善美
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡（福岡県）
• [Presentation] D-アミノ酸代謝システムの活性制御による新規精神神経疾患治療戦略 (2011)
  • Author(s): 福井清
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2011-09-24
• [Presentation] 新規アポトーシス/NF-κB制御分子ヌクリングの機能解析 (2011)
  • Author(s): 坂井隆志
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2011-09-23
• [Presentation] Combination of oxidative stress and energy depletion induced significant glioma cell death (2011)
  • Author(s): Salah M.EL-SAYED
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2011-09-23
• [Presentation] ヒトD-アミノ酸酸化酵素のグリア細胞内における機能解析 (2011)
  • Author(s): 宍戸裕二
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2011-09-23
• [Presentation] 新規アポトーシス/ NF-κB制御分子ヌクリングの機能解析 (2011)
  • Author(s): 坂井隆志
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2011-09-13
• [Presentation] アストログリア細胞内のD-アミノ酸酸化酵素によりD-セリンから産生されるヒドロキシピルビン酸の細胞死誘導活性 (2011)
  • Author(s): 鄭丞弼
  • Organizer: 第7回D-アミノ酸研究会学術講演会
  • Place of Presentation: 東京医科歯科大学(東京都)
  • Year and Date: 2011-09-10
• [Presentation] D-アミノ酸酸化酵素の遺伝子導入により、グリオーマ細胞では、3-ブロモピルビン酸の解糖系への阻害作用が増強される (2011)
  • Author(s): Salah M.El Sayed
  • Organizer: 第7回D-アミノ酸研究会学術講演会
  • Place of Presentation: 東京医科歯科大学(東京都)
  • Year and Date: 2011-09-10
• [Presentation] Modulation of D-amino acid oxidase activity as a novel strategy for the treatment of psychiatric disorders (2011)
  • Author(s): Fukui Kisyohi
  • Organizer: Function and dysfunction of D←amino acids in the central nervous system
  • Place of Presentation: 東京医科歯科大学(東京都)(招待講演)
  • Year and Date: 2011-09-10
• [Presentation] D-アミノ酸酸化酵素の活性制御による新規精神神経疾患治療戦略 (2011)
  • Author(s): 福井清
  • Organizer: 第7回D-アミノ酸研究会学術講演会
  • Place of Presentation: 東京医科歯科大学(東京都)
  • Year and Date: 2011-09-09
• [Presentation] グリア細胞におけるD-アミノ酸酸化酵素の機能解析 (2011)
  • Author(s): 宍戸裕二
  • Organizer: 第7回D-アミノ酸研究会学術講演会
  • Place of Presentation: 東京医科歯科大学(東京都)
  • Year and Date: 2011-09-09
• [Presentation] 新規NF-kB制御分子ヌクリングの免疫系における役割の検討 (2011)
  • Author(s): 金善美
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島大学(広島県)
  • Year and Date: 2011-05-14
• [Presentation] D-amino acid oxidase gene therapy sensitizes glioma cells to the anti-glycolytic effect of 3-bromopyruvate (2011)
  • Author(s): Salah M.El Sayed
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島大学(広島県)
  • Year and Date: 2011-05-14
• [Presentation] 新規NF-・B制御分子ヌクリングの免疫系における役割の検討 (2011)
  • Author(s): 金善美
  • Organizer: 第52回日本生化学会 中国・四国支部例会
  • Place of Presentation: 広島市
  • Year and Date: 2011-05-13
• [Presentation] Intracellular metabosim of Nucling, a novel apoptosis regulator (2010)
  • Author(s): Nam Hoang Tran
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 2010-12-09
• [Presentation] Intracellular metabolism of Nucling, a novel apoptosis regulator (2010)
  • Author(s): Sakai T
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-12-08
• [Presentation] Physiological function of a novel NF-・B-regulating molecule, Nucling, in immune system (2010)
  • Author(s): 金善美
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-12-08
• [Presentation] Physiological Function of a novel NF-κB-regulating molecule, NUCLING, in Immune system (2010)
  • Author(s): Sun Mi Kim
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 2010-12-08
• [Presentation] Nucling a novel apoptosis-associating protein, regulates NF-kB pathway (2010)
  • Author(s): Takashi Sakai
  • Organizer: The 12th IUBMB, 21st FAOBMB & ComBio2010 Conferences
  • Place of Presentation: Melbourne convention and Exhibition Centre(オーストラリア・メルボルン市)
  • Year and Date: 2010-09-29
• [Presentation] D-amino acid oxidase : pathophysiological basis and moleculaz target for schizophrenia (2010)
  • Author(s): Kiyoshi Fukui
  • Organizer: The 12th IUBMB, 21st FAOBMB & ComBio2010 Conferences
  • Place of Presentation: Melbourne convention and Exhibition Centre(オーストラリア・メルボルン市)
  • Year and Date: 2010-09-28
• [Presentation] Nucling, a novel apoptosis-associating protein, regulates NF-・B pathway、OzBio2010 (2010)
  • Author(s): Sakai, T.
  • Organizer: the 12th IUBMB, 21st FAOBMB & ComBio2010 Conferences
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2010-09-27
• [Presentation] Physiological function of a novel NF-・B-regulating molecule, Nucling, in immune system 、OzBio2010 (2010)
  • Author(s): Kim S. M
  • Organizer: the 12th IUBMB, 21stFAOBMB & ComBio2010 Conferences
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2010-09-27
• [Presentation] Physiological Function of a Novel NF-κB-Regulating Molecule, Nucling, in Immune System (2010)
  • Author(s): Sun Mi Kim
  • Organizer: The 12th IUBMB, 21st FAOBMB & ComBio2010 Conferences
  • Place of Presentation: Melbourne convention and Exhibition Centre(オーストラリア・メルボルン市)
  • Year and Date: 2010-09-27
• [Presentation] 新規アポトーシス誘導因子Nuclingのホモシステイン代謝系における関与 (2010)
  • Author(s): 佐古有季哉
  • Organizer: 日本ビタミン学会第62回大会
  • Place of Presentation: アイーナ(盛岡市)
  • Year and Date: 2010-06-12
• [Presentation] 新規アホトーシス制御分子NuclingはNF-κB、プロテアソーム及びカスパーゼに制御される (2010)
  • Author(s): Tran Hoang Nam
  • Organizer: 第51回日本生化学会中国四国支部例会
  • Place of Presentation: 山口大学大学会館(山口市)
  • Year and Date: 2010-05-15
• [Presentation] 新規 NF-kB 制御分子ヌクリングの炎症性病態への関与についての検討
  • Author(s): 金 善美
  • Organizer: 第53回日本生化学会中国・四国支部例会
  • Place of Presentation: 岡山大学（岡山県）
• [Remarks]
  • URL: http://www.ier.tokushima-u.ac.jp/article/0017774.html
• [Remarks]
  • URL: http://www.ier.tokushima-u.ac.jp/article/0017774.html