Cell recognition and oligomerization of toxins via lipids rafts

• Project/Area Number: 18687007
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry
• Research Institution: Kyushu University
• Principal Investigator: KITADA Sakae Kyushu University, 大学院・理学研究院, 助教 (20284482)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥30,160,000 (Direct Cost: ¥23,200,000、Indirect Cost: ¥6,960,000); Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2007: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000); Fiscal Year 2006: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
• Keywords: 毒素 / 微生物 / がん / 細胞 / 膜 / Bacillus thuringiensis / パラスポリン / GPIアンカー型タンパク / 受容体 / 脂質ラフト / GPI アンカー型タンパク / Baccillus thuringiensis

Research Abstract

殺虫性微生物、バシラス・チュリンジェンシス(Bt菌)から、がん細胞に対して毒性を示す新しいBt菌毒素タンパク質(パラスポリン2)を発見した。なぜパラスポリン2はがん種細胞特異的に作用するのだろうか?今回の研究から、この毒素が細胞表面に存在する局所領域(脂質ラフト)へ結合して巨大な毒素分子複合体(オリゴマー)を形成すること、また、毒素と結合するがん細胞因子を発見した。この研究からがん細胞に特異的で人体に安全な抗がん基礎研究の進展が期待できる。

Research Products

• [Journal Article] Crystal Structure of the Parasporin-2 Bacillus thuringiensis Toxin That Recognizes Cancer Cells (2009)
  • Author(s): Akiba T., Abe Y., Kitada S., Kusaka Y., Ito A., Ichimatsu T., Katayama H., Akao T.,Higuchi K., Mizuki E., Ohba M., Kanai R.,Harata K..
  • Journal Title: J. Mol. Biol 386 Pages: 121-133
• [Journal Article] Purification and characterization of human phosphatidylserine synthase 1 and 2 (2009)
  • Author(s): Tomohiro S., Kawaguti A., Kawabe Y., Kitada S., and Kuge O
  • Journal Title: Biochem J. 418 Pages: 421-429
• [Journal Article] Crystal Structure of the Parasporin-2 Bacillus thuringiensis Toxin That Recognizes Cancer Cells (2009)
  • Author(s): Akiba T., et.al.
  • Journal Title: J. Mol. Biol 386 Pages: 121-133
  • Peer Reviewed
• [Journal Article] Purification and characterization of human phosphatidylserine synthases 1 and 2 (2009)
  • Author(s): Tomohiro S., et.al.
  • Journal Title: Biochem J. 418 Pages: 418-418
  • Peer Reviewed
• [Journal Article] Raft-targeting and Oligomerization of Parasporin-2, a Bacillus thuringiensis Crystal Protein with Anti-tumor Activity (2008)
  • Author(s): Abe, Y., Shimada, Y., and Kitada, S
  • Journal Title: J. Biochem. 143 Pages: 269-269
• [Journal Article] Raft-targeting and Oligomerization of Parasporin-2, a Bacillus thuringiensis Crystal Protein with Anti-tumor Activity (2008)
  • Author(s): Abe, Y・Shimada, Y・Kitada, S
  • Journal Title: Journal of Biochemistry 143 Pages: 269-275
  • Peer Reviewed
• [Journal Article] Spatial orientation of mitochondrial processing peptidase and a preprotein revealed by fluorescence resonance energy transfer (2007)
  • Author(s): Tomonori G. Nishino, T. G., Katsuhiko. K., Kojima, K., Ogishima, T., Ito, A., and Kitada, S.
  • Journal Title: J. Biochem 141 Pages: 889-895
  • NAID: 10020098777
• [Journal Article] A Protein from a Parasitic Microorganism, Rickettsia prowazekii, Can Cleave the Signal Sequences of Proteins Targeting Mitochondria (2007)
  • Author(s): Kitada, S., et al(他5名).
  • Journal Title: J Bacteriol 189 Pages: 844-850
• [Journal Article] Spatial orientation of mitochondrial processing peptidase and a preprotein revealed by fluorescence resonance energy transfer (2007)
  • Author(s): Tomonori, G・Nishino, T., G., Katsuhiko・K, Kojima・K, Ogishima・T, Ito・A・Kitada, S.
  • Journal Title: Journal of Biochemistry 141 Pages: 889-895
  • NAID: 10020098777
  • Peer Reviewed
• [Journal Article] A Protein from a Parasitic Microorganism, Rickettsia prowazekii, Can Cleave the Signal Sequences of Proteins Targeting Mitochondria. (2007)
  • Author(s): Kitada S, Uchiyama T, Funatsu T, Kitada Y, Ogishima T, Ito A
  • Journal Title: Journal of Bacteriology. 189 Pages: 844-850
• [Journal Article] Cytocidal Actions of Parasporin-2, an Anti-tumor Crystal Toxin from Bacillus thuringiensis (2006)
  • Author(s): Kitada, S., et al(他13名).
  • Journal Title: J. Biol. Chem. 281 Pages: 26350-26360
• [Journal Article] Cytocidal Actions of Parasporin-2, an Anti-tumor Crystal Toxin from Bacillus thuringiensis. (2006)
  • Author(s): Kitada, S., Abe, Y., Shimada, H., Kusaka, K., Matsuo, M., Katayama, H., Okumura, S., Akao, T., Mizuki, E., Kuge, O., Sasaguri, Y., Ohba, M., Ito A.
  • Journal Title: Journal of Biological. Chemistry 281 Pages: 26350-26360
• [Presentation] 微生物毒素パラスポリン2のがん細胞破壊作用におけるGPIアンカー型タンパク質の関与 (2008)
  • Author(s): 阿部雄一、嶋田拡靖、芦田久、前田裕輔、木下タロウ、久下理、北田栄
  • Organizer: 第30回日本分子生物学会年会、第80回日本生化学会大会、合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2008-12-14
• [Presentation] 網羅的なヒト遺伝子発現抑制系を利用した、抗がん性毒素パラスポリン2耐性HepG2細胞の単離と性質 (2008)
  • Author(s): 前田敏孝、阿部雄一、久下理、北田栄
  • Organizer: BMB2008日本分子生物学会、日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 抗腫瘍性毒素Parasporin-2はHepG2細胞由来のタンパク質を含んだ超分子複合体を生体膜で形成する (2008)
  • Author(s): 嶋田拡靖、阿部雄一、久下理、北田栄
  • Organizer: BMB2008日本分子生物学会、日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 抗腫瘍性毒素parasporin-2はHepG2糸田胞由来のタンパク質を含んだ超分子複合体をせいたいまくで形成する (2008)
  • Author(s): 嶋田拡靖, et.al.
  • Organizer: BMB2008(日本分子生物学会年会・日本生化学会大会)
  • Place of Presentation: 神戸市
  • Year and Date: 2008-12-11
• [Presentation] Bacillus thuringiensis由来パラスポリン2毒素小孔の電気生理学的性状調査 (2008)
  • Author(s): 大串彰、北田栄、Marc Juteau 、Jean-Louis Schwartz
  • Organizer: BMB2008日本分子生物学会、日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Parasporin-2はHepG2細胞由来のタンパク質を含んだ超分子複合体を生体膜で形成する (2008)
  • Author(s): 嶋田拡靖、阿部雄一、久下理、北田栄
  • Organizer: 第3回パラスポリン研究会
  • Place of Presentation: 福岡
  • Year and Date: 2008-10-24
• [Presentation] 膜孔形成オリゴマー化毒素は細胞膜で巨大な毒素複合体を形成する (2007)
  • Author(s): 嶋田拡靖,阿部雄一,久下理,永浜政博,櫻井純,北田栄
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] Cell-binding and oligomerization of parasporin-2 are mediated by glycosylphosphatidylinositol-anchored proteins. (2007)
  • Author(s): Abe Y., Inoue H., Shimada H., Ashida H, Kinoshita T., Kuge O. and Kitada S.
  • Organizer: 40th Annual Meeting of the Society for Invertebrate Pathology
  • Place of Presentation: ケベックシティー、カナダ
  • Year and Date: 2007-08-15
• [Presentation] Mega assemblage of a mammalian cell-targeting and pore-forming toxin parasporin-2 from Bacillus thuringiensis. (2007)
  • Author(s): Hiroyasu Shimada, Yuichi Abe, Osamu Kuge, and Sakae Kitada
  • Organizer: 40th Annual Meeting of the Society for Invertebrate Pathology
  • Place of Presentation: ケベックシティー、カナダ
  • Year and Date: 2007-08-13
• [Presentation] an anti-tumor crystal toxin from Bacillus thuringiensis (2006)
  • Author(s): Sakae Kitada, Parasporin
  • Organizer: GEPROM conferences
  • Place of Presentation: モントリオール、カナダ
  • Year and Date: 2006-12-12
• [Presentation] 脂質ラフトを標的とし多量体化する毒素parasporin-2は細胞膜中で超分子複合体を形成する (2006)
  • Author(s): 嶋田拡靖、阿部雄一、久下理、北田栄
  • Organizer: 第2回パラスポリン研究会
  • Place of Presentation: 福岡
  • Year and Date: 2006-10-19
• [Presentation] パラスポリン2の細胞認識におけるGPIアンカータンパク質の関与 (2006)
  • Author(s): 阿部雄一、井上大志、嶋田拡靖、芦田久、木下タロウ、久下理、北田栄
  • Organizer: 第2回パラスポリン研究会
  • Place of Presentation: 福岡
  • Year and Date: 2006-10-19
• [Presentation] Michio Ohba and Akio Ito : Cytocidal actions of parasporin-2, a novel crystal toxin targeting human cancer cells from Bacillus thuringiensis. (2006)
  • Author(s): Sakae Kitada, Yuichi Abe, Hiroyasu Shimada, Osamu Kuge, Eiichi Mizuki
  • Organizer: XXXIX Annual Meeting of the Society for Invertebrate Pathology
  • Place of Presentation: 武漢、中国
  • Year and Date: 2006-08-28
• [Presentation] GPI-anchored proteins are involved in the cytocidal actions of parasporin-2, a mammalian cell-targeting crystal protein from Bacillus thuringiensis A1547 (2006)
  • Author(s): Yuichi Abe, Hiroshi Inoue, Hiroyasu Shimada, Michio Ohba, Hisashi Ashida, Taroh Kinoshita, Osamu Kuge and Sakae Kitada
  • Organizer: XXXIX Annual Meeting of the Society for Invertebrate Pathology
  • Place of Presentation: 武漢、中国
  • Year and Date: 2006-08-28
• [Presentation] Parasporin-2, an oligomerizing and pore-forming toxin from Bacillus thuringiensis, is assembled into supramolecular complexes in target human cell membranes. (2006)
  • Author(s): Hiroyasu Shimada, Yuichi Abe, Osamu Kuge and Sakae Kitada
  • Organizer: XXXIX Annual Meeting of the Society for Invertebrate Pathology
  • Place of Presentation: 武漢、中国
  • Year and Date: 2006-08-28
• [Presentation] Parasporin-2, a lipid laft targeting and oligomerizing cytotoxin from Bacillus thuringiensis, is assembled into supramolecular complex on the target plasma membrane. (2006)
  • Author(s): Hiroyasu Shimada, Yuichi Abe, Osamu Kuge, Sakae Kitada
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB
  • Place of Presentation: Congress
  • Year and Date: 2006-06-21
• [Presentation] GPI-anchored proteins mediate cell-binding and oligomerization of parasporin-2, a new crystal toxin targeting mammalian cells from Bacillus thuringiensis. (2006)
  • Author(s): Yuichi Abe, Hroshi Inoue, Hroyasu Shimada, Hisashi Ashida, Tarih Kinoshita, Osamu Kuge, and Sakae Kitada
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB
  • Place of Presentation: Congress
  • Year and Date: 2006-06-21
• [Book] 細菌毒素のパラドックス「毒素が薬に食物に?生命科学への応用について」、生物の科学遺伝、3月号 (2009)
  • Author(s): 北田栄、嶋田擴靖
  • Publisher: エヌ・ティー・エス出版
• [Book] 生物の科学遺伝細菌毒素のパラドックス「毒素が薬に食物に? 生命科学への応用について」 (2009)
  • Author(s): 北田栄, et.al.
  • Total Pages: 9
  • Publisher: エヌ・ティー・エス出版
• [Remarks] 九州大学教育拠点形成プログラム
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• [Remarks] パラスポリン研究会
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• [Remarks] 九州大学研究者情報
  • URL: http://hyoka.ofc.kyushu-u.ac.jp/search/details/K000757/index.html
• [Remarks]
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• [Remarks]
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• [Remarks]
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