動物細胞の細胞周期調節遺伝子の分離とその機能の研究

• 研究課題/領域番号: 03454560
• 研究種目: 一般研究(B)
• 配分区分: 補助金
• 研究分野: 分子遺伝学・分子生理学
• 研究機関: 九州大学
• 研究代表者: 西本 毅治 九州大学, 大学院医学系研究科, 教授 (10037426)
• 研究期間 (年度): 1991 – 1993
• 研究課題ステータス: 完了 (1993年度)
• 配分額: 6,200千円 (直接経費: 6,200千円); 1993年度: 2,000千円 (直接経費: 2,000千円); 1992年度: 2,000千円 (直接経費: 2,000千円); 1991年度: 2,200千円 (直接経費: 2,200千円)
• キーワード: 細胞周期 / CCG1 / RCC1 / RPS4X / DAD1 / CDC25 / PCC / G2ブロック / 温度感受性変異 / DADl / CCGl / 温度感受性変異株 / CCG2(RPS4X) / アポトーシス / CCG2

研究概要

ハムスター由来の継代培養細胞株BHK21より分離された細胞増殖に関する温度感受性変異株を用いて変異を相補するヒト遺伝子を分離し、そのcDNAを得ることをこの研究の第一歩とし、これまで研究してきた。
本研究の最終年度にあたりこれまでの成果をまとめると以下のようになる。
1.RCC1遺伝子に関して
1)この遺伝子が機能的に保存されていること。
2)ヒトRCC1の全塩基配列を決定。
3)DNA結合ドメインの同定。
4)cdc25CとtsBN2変異の相関。
5)RCC1とRanタンパクの精製とその化学的性質の研究。
2.完全なCCG1cDNAの分離
3.新たな遺伝子の分離:RPS4X、DAD1
4.G2ブロックとユビキチン活性化酵素E1との相関の解明

研究成果

• [文献書誌] M.Ohtsubo: "Mutation of the hamster cell cycle gene RCC1 is complemented by the homologous genes of Drosophila and S.cerevisiae." EMBO J. 10. 1265-1273 (1991)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] T.Sekiguchi: "The human CCG1 gene,essential for progression of the G1 phase,encodes a210-kDa Nuclear DNA-binding protein." Mol.Cell.Biol. 11. 3317-3325 (1991)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] N.Furuno: "Complete nucleotide sequence of the human RCC1 gene involved in coupling between DNA replication and Mitosis." GENOMICS. 11. 459-461 (1991)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] M.Watanabe: "Molecular cloning of the human gene,CCG2,that complements the BHK-derived tempaerature-sensitive cell cycle mutant tsBN63:identity of CCG2 with the human X chromosomal SCAR/RPS4X gene." J.Cell.Science. 100. 35-43 (1991)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Seki,T.,Nishimoto,T.et al: "Chromosome condensation caused by loss of RCC1 function requires the cec25C protein that is located in the cytoplasm." Mol.Biol.Cell.3. 1373-1388 (1992)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Seino,H.,Nishimoto,T.et al: "DNA-Binding domein of RCC1 protein is not essential for coupling with DNA replication." J.Cell Science. 102. 393-400 (1992)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Nishitani,H.,Nishimoto,T.et al: "tsBN75 and tsBN423,temperature-sensitive X-linked mutant of the BHK21 cell line,can be complemented by the ubiquitin-activating enzyme E1 cDNA." Biochem.Biophys.Res.Commun.184. 1015-1021 (1992)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Watanabe,M.,Nishimoto,T.et al.: "Functional equivalence of human X- and Y-encoded isoforms of ribosomal protein S4 consistent with a role in Tumer syndrome." Nature Genetics. 4. 268-271 (1993)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Nakashima,T.,Nishimoto,T.et al.: "Molecular cloning of a human cDNA encoding a novel protein,DAD1,whose defect causes apoptotic cell death in hamster BHK21 cells." Mol.Cell.Biol.13. 6367-6374 (1993)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Klebe,C.,Nishimoto,T.,et al.: "Functional expression in E.coli of the mitotic regulator proteins p24ran and p45RCC1 and fluorescence measurements of their interaction." Biochemistry. 11923-11928 (1993)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] M.Ohtsubo, T.Yoshida, H.Seino, H.Nishitani, K.Clark, G.Sprague, M.Frasch and T.Nishimoto.: "Mutation of the hamster cell cycle gene RCC1 is complemented by the homologous genes of Drosophila and S.cerevisiae." EMBO J. 10. 1265-1273 (1991)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] T.Sekiguchi, Y.Nohiro, Y.Nakamura, N.Hisamoto and T.Nishimoto.: "The human CCG1 gene, essential for progression of the G1 phase, encodes a 210-kilodalton nuclear DNA-binding protein. Mol. cell. biol. 11, 3317-3325." Mol. cell. Biol. 11. 3317-3325 (1991)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] M.Watanabe, N.Furuno, M.Goebl, M.Go, K.Miyauchi, T.Sekiguchi, C.Basilico and T.Nishimoto.: "Molecular cloning of the human gene, CCG2, that complements the BHK-derived temperature-sensitive cell cycle mutant tsBN63 : identity of CCG2 with the human X chromosomal SCAR/RPS4X gene." J.Gell Science. 100. 35-43 (1991)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] N.Furuno, K.Nakagawa, U.Eguchi, M.Ohtsubo, T.Nishimoto and E.Soeda.: "Complete nucleotide sequence of the human RCC1 gene involved in coupling between DNA replication and Mitosis." Genomics. 11. 459-461 (1991)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] H.Nishitani, H.Goto, S.Kaneda, F.Yamao, T.Seno, P.Handley, A.L.Schwartz and T.Nishimoto: "tsBN75 and tsBN423, temperature-sensitive X-linked mutant of the BHK21 cell line, can be complemented by the ubiquitinactivating enzyme E1 cDNA." BioChem. Biophys. Res. Commun. 184. 1015-1021 (1992)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] H.Seino, N.Hisamoto, S.Uzawa, T.Sekiguchi, and T.Nishimoto: "DNA-binding domain of RCC1 protein is not essential for coupling mitosis with DNA replication." J.Gell Science. 102. 393-400 (1992)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] T.Seki, K.Yamashita, H.Nishitani, T.Takagi, P.Russell and T.Nishimoto: "Chromosome condensation caused by loss of RCC1 function requires the cdc25C protein that is located in the cytoplasm." Mole. Biol. Cell. 3. 1373-1388 (1992)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] M.Watanabe, A.R.Zinn, D.C.Page, and T.Nishimoto: "Functional equivalence of human X- and Y-encoded isoforms of ribosomal protein S4 consistent with a role in Turner syndrome." Nature Genetics. 4. 268-271 (1993)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] C.Klebe, T.Nishimoto and F.Wittinghofer: "Functional Expression in E.coli of the mitotic regulator proteins p24ran and p45rccl and fluorescence measurements of their interaction." Biochemistry. 32. 11923-11928 (1993)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] T.Nakashima, T.Sekiguchi, A.Kuraoka, K.Fukushima, Y.Shibata, S.Komiyama, and T.Nishimoto: "Molecular cloning of a human cDNA encoding a Novel Protein, DAD1 whose defect causes apoptotic cell death in Hamster BHK21 cells." Mol. Cell. Biol. 13. 6367-6374
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Watanabe,M.,Nishimoto,T.et al.: "Functional equivalencen of human X-and Y-encoded isoforms of ribosomal protein S4 consistent with a role in Tumer syndrome." Nature Genetics. 4. 268-271 (1993)
• [文献書誌] Nakashima,T.,Nishimoto,T.et al.: "Molecular cloning of a human cDNA encoding a novel protein,DAD1,whosedefect causes apoptotic cell death in hamster BHK21 cells." Mol.Cell.Biol.13. 6367-6374 (1993)
• [文献書誌] Klebe,C.,Nishimoto,T.,et al.,: "Functional expression in E.coli of the mitotic regulator proteins p24ran and p45RCC1 and fluorescence measurements of their interaction." Biochemistry. 32. 11923-11928 (1993)
• [文献書誌] Hayashida,T.Nishimoto,T.,et al.: "The CCG1/TAFII250 gene is mutated in thermosensitive G1 mutation of the BHK21 cell line derived from golden hamster." Gene. (in press). (1994)
• [文献書誌] Seki,T.,Nishimoto,T.et al: "Chromosome condensation caused by loss of RCC1 function requires the cec25C protein that is located in the cytoplasm." Mol.Biol.Cell.3. 1373-1388 (1992)
• [文献書誌] Seino,H.,Nishimoto,T.et al: "DNA-Binding domein of RCC1 protein is not essential for coupling with DNA replication." J.Cell Science. 102. 393-400 (1992)
• [文献書誌] Nishitani,H.,NIshimoto,T.et al: "tsBN75 and tsBN423,temperature-sensitive X-linked mutant of the BHK21 cell line,can be complemented by the ubiquitin-activating enzyme E1 cDNA." Biochem.Biophys.Res.Commun.184. 1015-1021 (1992)
• [文献書誌] M.Ohtsubo: "Mutation of the hamster cell cycle gene RCC1 is complemented by the homologous genes of Drosophila and S.cerevisiae." EMBO J. 10. 1265-1273 (1991)
• [文献書誌] T.Sekiguchi: "The human CCG1 gene,essential for progression of the G1 phase,encodes a210ーkDa Nuclear DNAーbinding protein." Mo1.Cell.Bio1. 11. 3317-3325 (1991)
• [文献書誌] N.Furuno: "Complete nucleotide sequence of the human RCC1 gene involved in coupling between DNA replication and Mitosis." GENOMICS. 11. 459-461 (1991)
• [文献書誌] M.Watanabe: "Molecular cloning of the human gene,CCG2,that Complements the BHKーderived tempaeratureーsensitive cell cycle mutant tsBN63:identity of CCG2 with the human X chromosomal SCAR/RPS4X gene." J.Cell.Science. 100. 35-43 (1991)