ABC蛋白の多機能性と生命維持機構

• Project/Area Number: 10217101
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: 植田 和光 京都大学, 農学研究科, 教授 (10151789)
• Co-Investigator(Kenkyū-buntansha): 稲垣 暢也 秋田大学, 医学部, 教授 (30241954) ; 木岡 紀幸 京都大学, 農学研究科, 助教授 (90234179) ; 中西 重忠 京都大学, 医学研究科, 教授 (20089105) ; 井村 裕夫 (井村 浩夫) 京都大学, 名誉教授 (10025570) ; 永田 和宏 京都大学, 再生医科学研究所, 教授 (50127114) ; 鶴尾 隆 東京大学, 分子細胞生物学研究所, 教授 (00012667)
• Project Period (FY): 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥52,100,000 (Direct Cost: ¥52,100,000); Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000); Fiscal Year 2002: ¥11,800,000 (Direct Cost: ¥11,800,000); Fiscal Year 2001: ¥9,900,000 (Direct Cost: ¥9,900,000); Fiscal Year 2000: ¥9,900,000 (Direct Cost: ¥9,900,000); Fiscal Year 1999: ¥9,300,000 (Direct Cost: ¥9,300,000); Fiscal Year 1998: ¥9,700,000 (Direct Cost: ¥9,700,000)
• Keywords: ABC蛋白質 / 生活習慣病 / コレステロール / 糖尿病 / 癌 / トランスポーター / ABCタンパク質 / チャネル / 動脈硬化 / 膜タンパク質 / 構造解析 / 遺伝病 / ATP / レセプター

Research Abstract

ABC蛋白は、1機能分子内によく保存されたATP結合部位を2つ有する膜蛋白の総称であり、多様な生理機能を示し、生命維持に必須な役割を果たしている。本特定領域研究では、多分野の研究者が有機的に協力し、ABC蛋白の機能の多様性、多機能性の分子基盤、生理的重要性の解明をおこなった。
本年は、5年間の研究の取りまとめをおこなった。
平成16年3月5日に秋田大学医学部において公開シンポジウム「ABC蛋白の多機能性と生命維持機構」を開催し、成果を社会に広く公開した。
研究成果は学術図書として出版するため、平成16年度学術図書出版を申請した。

Research Products

• [Publications] Abe-Dohmae S.: "Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate HDLA"J Biol Chem. 279. 604-611 (2004)
• [Publications] Ikeda Y.: "Post-transcriptional regulation of human ABCA7 and its function for the apoA-I-dependent lipid release"Biochem Biophys Res Commun. 311. 313-318 (2003)
• [Publications] Tanaka, A.R.: "Effects of mutations of ABCA1 in the first extracellular domain on subcellular trafficking and ATP binding/hydrolysis"J Biol Chem. 278. 8815-8819 (2003)
• [Publications] Shitan, N.: "Involvement of CjMDR1, a plant MDR-type ABC protein, in alkaloid transport in Coptis japonica."Proc.Natl.Acad.Sci.USA. 100. 751-756 (2003)
• [Publications] Kimura, Y.: "Microanalysis for MDR1 ATPase by high-performance liquid chromatography with a titanium dioxide column"Anal.Biochem. 326. 262-266 (2004)
• [Publications] Kimura, Y.: "ATP hydrolysis-dependent multidrug efflux transporter, MDR1/P-glycoprotein."Current Drug Metabolism. 5. 1-10 (2004)
• [Publications] Tanaka, A.R.: "Effects of mutations of ABCA1 in the first extracellular domain on subcellular trafficking and ATB binding/hydrolysis"J Biol Chem.. 278. 8815-8819 (2003)
• [Publications] Shitan, N.: "Involvement of CjMDR1, a plant MDR-type ABC protein, in alkaloid transport in Coptis japonica"Proc. Natl. Acad. Sci. USA. 100. 751-756 (2003)
• [Publications] Sugimoto, Y.: "Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists"Mol. Cancer Ther.. 2. 105-112 (2003)
• [Publications] Tanaka, A.R.: "ATP binding/hydrolysis by and phosphorylation of peroxisomal ABC proteins PMP70(ABCD3) and ALDP(ABCD1)"J Biol Chem.. 277. 40142-40147 (2002)
• [Publications] Matsuo, M.: "Mutations in the linker domain of NBD2 of SUR inhibit transduction but not nucleotide binding"EMBOJ. 21. 4250-4258 (2002)
• [Publications] Hashimoto, K.: "Trafficking-defect and functional-defect by mutations of the ATP-binding domains in multidrug resistance protein 2 (MRP2, ABCC2) in patients with Dubin-Johnson syndrome"Hepatology. 36. 1246-1252 (2002)
• [Publications] 稲垣暢也: "ABCトランスポーター-生体防御のABC-遺伝子からの疾患まで"診断と治療社. 82 (2002)
• [Publications] Tanaka, A.R.: "Human ABCA1 Contains a Large Amino-Terminal Extracellular Domain Homologous to an Epitope of Sjogren's Syndrome"Biochem. Biophys. Res. Commun.. 283. 1019-1025 (2001)
• [Publications] Chen, Z.: "Reversal of drug resistance mediated by multidrug resistance protein(MRP)1 by dual effects of agosterol a on MRP1 function"Int. J. Cancer. 93. 107-113 (2001)
• [Publications] Yazaki, K.: "A novel Coptis japonica multidrug resistant protein preferentially expressed in the alkaloid-accumulating rhizome"J. Exp. Bot.. 357. 877-879 (2001)
• [Publications] 植田和光: "多剤排出トランスポーターMDR1の分子機構? 生体防御ABC"蛋白質 核酸 酵素. 46. 588-595 (2001)
• [Publications] 植田和光: "ABCA1蛋白質の構造と機能"The Lipid. 13. 42-48 (2002)
• [Publications] 稲垣暢也: "ABCトランスポーター-生体防御のABC-遺伝子から疾患まで"診断と治療社. 82 (2002)
• [Publications] Matsuo,M.: "Different binding properties and affinities for ATP and ADP among sulfonylurea receptor subtypes, SUR1, SUR2A, and SUR2B."J.Biol.Chem.. 275. 28757-28763 (2000)
• [Publications] Matsuo,M.: "Functional analysis of a mutant sulfonylurea receptor, SUR1-R1420C, that is responsible for persistent hyperinsulinemic hypoglycemia of infancy."J.Biol.Chem.. 275. 41184-41191 (2000)
• [Publications] Nagata,K: "Nonequivalent Nucleotide Trapping in the Two Nucleotide Binding Folds of the Human Multidrug Resistance Protein MRP1"J.Biol.Chem.. 275. 17626-17630 (2000)
• [Publications] Tanizawa,Y.: "Genetic analysis of Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy : nucleotide-binding fold-2 mutation impairs cooperative binding of adenine nucleotides to SUR1"Diabetes. 49. 114-20 (2000)
• [Publications] Tanabe,K: "Direct Photoaffinity Labeling of Kir6.2 by [γ-32P]ATP-[γ]4-Azidoanilide."Biochem.Biophys.Res.Commun.. 272. 316-319 (2000)
• [Publications] Zhao,L.-X.,: "Cloning, characterization, and tissue distribution of the ABC transporter ABC2."Biochem,J.,. 350. 865-872 (2000)
• [Publications] Ueda,K.: "How do P-glycoprotein and other ABC proteins recognize their substrates? In The first International Conference on Cotrol and Diseases of Sodium Dependent Transportation Proteins and Ion Channels."Amsterdam : Elsevier. 425-428 (2000)
• [Publications] Ueda, K.: "Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide"Proc. Natl. Acad. Sci. USA. 96. 1268-1272 (1999)
• [Publications] Matsuo, M.: "ATP binding properties of the nucleotide binding folds of SUR1"J. Biol. Chem.. 274. 37479-37482 (1999)
• [Publications] Tanabe, K.: "Direct Photoaffinity Labelling of the Kir6.2 subunit of the ATP-sensitive K+ channel by 8-Azido-ATP"J. Biol. Chem.. 274. 3931-3933 (1999)
• [Publications] Akamatsu, M.: "Vinexin Forms a Signaling Complex with Sos and Modulates Epidermal Growth Factor-induced c-Jun N-terminal Kinase/Stress-activated Protein Kinase Activities"J. Biol. Chem.. 274. 35933-35937 (1999)
• [Publications] Ueda, K.: "Comparative aspects of the function and mechanism of SUR1 and MDR1 proteins"Biochim. Biophys. Acta. 1461. 305-313 (1999)
• [Publications] Tanizawa, Y.: "Genetic analysis of Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy : nucleotide-binding fold-2 mutation impairs cooperative binding of adenine nucleotides to sulfonylurea receptor 1"Diabetes. 49. 114-120 (2000)
• [Publications] Ashizawa, T.: "Antinumor activity of KF22678, a novel thioester derivative of leinamycin"Anticancer Drugs. 10. 829-836 (1999)
• [Publications] Chen, Z.: "ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P"Mol Pharmacol. 55. 921-928 (1999)
• [Publications] Matsuo, M.: "NEM modification prevents high-affinity ATP-binding to the first nucleotide binding fold of the sulphonylurea receptor, SUR1"FEBS Lett. 458. 292-294 (1999)
• [Publications] Tsuruoka, S.: "Removal of digoxin and doxorubicin by multidrug resistance protein-overexpressed cell culture in hollow fiber"Kidney Int. 56. 154-163 (1999)
• [Publications] Ueda, K.: "Recent progress in P-glycoprotein research"Anti-cancer drug design. 14. 115-121 (1999)
• [Publications] Nishii, Y.: "CROP/Luc7A, a novel serine/Arginine-rich nuclear protein, isolated from cisplatin resistant cell line"FEBS Lett.. 465. 153-156 (2000)
• [Publications] Takada,Y.: "Non-equivalent cooperation between the two nucleotide-binding folds of P-glycoprotein." Biochim.Biophys.Acta. 1373. 131-136 (1998)
• [Publications] Kusunoki,N.: "Inhibitory effects of a cyclosporin derivative, SDZ PSC 833, on transport of doxorubicin and vinblastine via human P-glycoprotein." Jpn.J.Cancer Res.89. 1220-1228 (1998)
• [Publications] Tanabe,K.: "Direct Photoaffinity Labelling of the Kir6.2 subunit of the ATP-sensitive K+ channel by 8-Azido-ATP." J.Biol.Chem.274. 3931-3933 (1999)
• [Publications] Ueda,K.: "Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide." Proc.Natl.Acad.Sci.USA. 96. 1268-1272 (1999)
• [Publications] Ueda,K.: "Recent progress in P-glycoprotein research." Anti-cancer drug design. 14 (印刷中). (1999)